WO2021016477A1

WO2021016477A1 - Evaluation of safety risks

Info

Publication number: WO2021016477A1
Application number: PCT/US2020/043319
Authority: WO
Inventors: Libbe ENGLANDER; David Light
Original assignee: Pharm 3r LLC; Valisure LLC
Current assignee: Pharm 3r LLC; Valisure LLC
Priority date: 2019-07-24
Filing date: 2020-07-23
Publication date: 2021-01-28
Anticipated expiration: 2022-01-24

Abstract

A method for developing a risk score for a medical intervention, said method comprising: determining one or more characteristics of a sample of said medical intervention using an analytical technique and assigning a first value based on said one or more characteristics; and generating a risk score for said medical intervention based at least on said first value.

Description

EVALUATION OF SAFETY RISKS

CROSS-REFERENCE

[0001] This application claims the benefit of U.S. Provisional Application No. 62/878,191, filed July 24, 2019, and U.S. Provisional Application No. 62/988,301, filed March 11, 2020, which applications are incorporated herein by reference in their entirety.

BACKGROUND OF THE INVENTION

[0002] Adverse effects from drugs, vaccines, and devices approved by the US Food and Drug Administration (FDA), and other national and international regulatory bodies, are a major public safety concern. Methods and systems that evaluate adverse events and risks associated with medical products may alleviate such concerns.

SUMMARY OF THE INVENTION

[0003] Disclosed herein are methods comprising developing a risk score for a medical intervention. In some embodiments, a method can comprise determining one or more characteristics of a sample of a medical intervention using an analytical technique and assigning a first value based on one or more characteristics of the medical intervention. In some embodiments, a method can further comprise generating a risk score for the medical intervention based at least on the first value. In some embodiments, a medical intervention can be a pharmacological intervention. In some embodiments, a risk score can be based solely on a first value. In some embodiments, a method can further comprise assessing an additional criterion of a medical intervention. In some embodiments, an additional criterion can comprise safety related information, or physical data. In some embodiments, an additional criterion can comprise safety related information. In some embodiments, safety related information can comprise an adverse event data or patient outcome data. In some embodiments, a risk of a medical intervention can be increased based on a reporting of an adverse event or negative patient outcome. In some embodiments, a safety related information can be from one or more pharmacovigilance center.

In some embodiments, a pharmacovigilance center can comprise US FDA Adverse Event Reporting System (FAERS), Australia’s“Therapeutic Goods Administration,” Canada’s “Vigilance Adverse Reaction Online Database,” Europe’s“EudraVigilance,” Japan’s “Pharmaceuticals and Medical Devices Agency,” United Kingdom’s“Yellow Card Scheme,” France’s“pharmacovigilance database (ANSM),” or the World Health Organization’s “VigiBase.” In some embodiments, an additional criterion can comprise physical data. In some embodiments, a physical data can comprise abnormalities in: hardness, weight, density, size, shape, buoyancy, texture, color, turbidity, opacity, light reflection, dryness, hygroscopicity, static charge, conductivity, resistivity, magneticity, or any combination thereof. In some embodiments, one or more characteristics can comprise a presence or an absence of an impurity or a contaminant. In some embodiments, one or more characteristics can comprise a quantity of an impurity or contaminant. In some embodiments, an impurity or contaminant can be a disease causing impurity or contaminant. In some embodiments, a risk of a medical intervention can be increased based on a presence of an impurity or contaminant. In some embodiments, risk of a medical intervention can be decreased based on an absence of a impurity or contaminant. In some embodiments, one or more characteristics can comprise a quantity of an active

pharmaceutical ingredient. In some embodiments, a risk of medical intervention can be increased when active pharmaceutical ingredient is above or below a manufacturer or a regulatory agency specification. In some embodiments, risk of medical intervention can be decreased when active pharmaceutical ingredient is within a manufacturer or a regulatory agency specification. In some embodiments, one or more characteristics can comprise a measure of dissolution of a pharmaceutical ingredient. In some embodiments, one or more characteristics can comprise a measure of: an active pharmaceutical ingredient, dissolution of a pharmaceutical ingredient, an inactive ingredient, an impurity, contaminant, a carcinogen, heavy metal, microbial contamination, residual solvent, outgassing product, particulates, foreign object, volatile compound, cross contamination of a pharmaceutical ingredient or any combination thereof. In some embodiments, a risk score can be provided to a subject. In some embodiments, the analytical technique can be nuclear magnetic resonance spectroscopy, mass spectroscopy, high-performance liquid chromatography, Fourier transform infrared spectroscopy, or Raman spectroscopy. In some embodiments, disclosed herein can be a system for performing a method disclosed herein.

[0004] Disclosed herein are methods and systems for generating a risk score. In some embodiments, a method can comprise assessing safety related information for a medical intervention and assigning a first value based on a safety related information. In some embodiments, a method can comprise, determining one or more characteristics of a sample of a medical intervention and assigning a second value based on one or more characteristics. In some embodiments, a method can comprise generating a risk score for a medical intervention based on a first value and a second value. In some embodiments, a medical intervention can be a pharmacological intervention. In some embodiments, a safety related information can comprise adverse event data or patient outcome data. In some embodiments, a first value can be increased based on a reporting of an adverse event or negative patient outcome. In some embodiments, a safety related information can be from one or more pharmacovigilance center. In some embodiments, a pharmacovigilance center can comprise US FDA Adverse Event Reporting System (FAERS), Australia’s“Therapeutic Goods Administration,” Canada’s“Vigilance Adverse Reaction Online Database,” Europe’s“EudraVigilance,” Japan’s“Pharmaceuticals and Medical Devices Agency,” United Kingdom’s“Yellow Card Scheme,” France’s

“pharmacovigilance database (ANSM),” or the World Health Organization’s“VigiBase.” In some embodiments, one or more characteristics can comprise a presence or an absence of an impurity or a contaminant. In some embodiments, one or more characteristics can comprise a quantity of an impurity or a contaminant. In some embodiments, an impurity or a contaminant can be a disease causing impurity or contaminant. In some embodiments, a second value can be increased based on a presence of an impurity or a contaminant. In some embodiments, a second value can be decreased based on an absence of an impurity or a contaminant. In some embodiments, one or more characteristics can comprise a quantity of an active pharmaceutical ingredient. In some embodiments, a second value can be increased when an active

pharmaceutical ingredient is above or below a manufacturer or a regulatory agency

specification. In some embodiments, a second value can be decreased when an active pharmaceutical ingredient is within a manufacturer or a regulatory agency specification. In some embodiments, one or more characteristics can comprise a measure of dissolution of a pharmaceutical ingredient. In some embodiments, a second value can be increased when a measure of dissolution is above or below a manufacturer or a regulatory agency specification. In some embodiments, a second value can be decreased when a measure of dissolution is within a manufacturer or a regulatory agency specification. In some embodiments, determining one or more characteristics of a sample of a medical intervention can be performed using an analytical test. In some embodiments, an analytical test can be performed using a nuclear magnetic resonance spectroscopy, mass spectroscopy, high-performance liquid chromatography, Fourier transform infrared spectroscopy or Raman spectroscopy. In some embodiments, an analytical test can be performed using Raman spectroscopy. In some embodiments, an analytical test can comprise a plurality of analytical tests. In some embodiments, a risk score can be provided to a subject. In some embodiments, disclosed herein are systems for performing the methods disclosed herein.

INCORPORATION BY REFERENCE

[0005] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. BRIEF DESCRIPTION OF THE DRAWINGS

[0006] The novel features of the disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative

embodiments, in which the principles of the disclosure are utilized, and the accompanying drawings of which:

[0007] FIG. 1 shows example of real time updated quality scores and optional alerts for drug and manufacturer.

DEFINITIONS

[0008] Before describing exemplary embodiments in greater detail, the following definitions are set forth to illustrate and define the meaning and scope of the terms used in the description.

[0009] The terms“safety assessment” and“safety-related information” can refer to any information relating to the safety of a medical product or treatment, including safety-related severity, level of risk, side effect(s), unintended consequence(s), and the like relating to the use of a medical product or treatment in a patient, group of patients, or population.

[0010] The term“pharmacovigilance” can refer to the science and activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other drug related problem.

[0011]“Medical intervention” is a comprehensive term used to refer collectively to medical products and medical treatments. The term“medical product” or“product” can refer to any product such as a drug, vaccine, medication, dietary supplement, or medical device, including those used in a prophylactic manner, used to treat the cause or symptoms of a medical disease, disorder, or condition. The term“medical treatment” can refer to any treatment, including prophylactic treatment, of a medical disease, disorder, or condition using a drug, vaccine, medication, dietary supplement, or medical device.

[0012] The terms“adverse event database” or“safety-related database” can refer to any state, national, or international collection(s) of data, educational products, systems to analyze data, and/or programs to disseminate and/or catalog safety and/or adverse event information such as the US FDA Adverse Event Reporting System (FAERS), Australia's Therapeutic Goods Administration, Canada's Vigilance Adverse Reaction Online Database, Europe's

EudraVigilance, Japan's Pharmaceuticals and Medical Devices Agency, the United Kingdom's Yellow Card Scheme, France's pharmacovigilance database (ANSM), the World Health Organization's VigiBase, and any related collection(s) of safety data and/or side effect infonnation relevant to the treatment, or consequences of treatment, of a patient. The terms also are intended to refer to patient safety data derived from claims or clinical trial databases.

[0013] The term“combined”, in the context of combining values, can include summing, aggregating, multiplying, and any other mathematical procedure, including procedures that comprise weighting of input parameters, that results in a score, ranking, or the like, that estimates the safety of a medical product or treatment.

[0014] The terms“safety-related score” and“safety-related rank” can refer to any type of value that estimates the safety of a medical product or treatment. A safety-related score or rank may be quantitative or qualitative, and may be in the form of a number, letter, a word, a percentage, a ranking, etc., that allows one to compare the safety on one medical product or treatment to another.

[0015] The term“adverse event” can refer to any type of“side effect,” non-therapeutic event, or consequence that can be triggered by the use of a medical product or treatment, including, but not limited to, adverse consequences linked to, addiction, drug-drug interactions, special population reactions, dosing effects, etc.

[0016] The term“outcome” can refer to the state of a patient after, or during, an adverse reaction possibly linked to the use of a medical product or treatment. By way of example, this can be a field that a patient, medical provider, or pharmaceutical manufacturer fills out when completing an adverse event report in a database such as FAERS. Within FAERS, there are 7 different“outcomes” as defined by the US Food and Drug Administration (FDA): Death, Life- threatening, Hospitalization, Disability or Permanent Damage, Congenital Anomaly/Birth Defect, Required Intervention to Prevent Permanent Impairment or Damage (Devices), and Other Serious (Important Medical Events).

[0017] The term“Condition Seriousness” can refer to an assessment that takes into

consideration the weightiness, gravity, or severity of a patient's condition, state, or circumstance. As an example, the IME lists two main categories of "Condition Seriousness": "Not Serious" and "Serious Condition."

[0018] The term“Adverse Event Seriousness” can refer to the weightiness, gravity, or severity of an adverse event experienced by a subject. By way of example, EUDRA's Important Medical Events (IME) terms are classified into one of three categories of“seriousness” based on 15,000 preferred term classifications of adverse events. There are two categories of seriousness as defined by the IME lists: terms that would be "always" serious (Core List), and terms that "could be" serious or not according to the circumstances (Extended List). A third category can be used when the adverse event is missing from a case report. [0019] The term“Event Reporter” can refer to the person, or entity, that submitted a given safety-related or adverse event report. By way of example, for reports submitted to FAERS, manufacturers, physicians, pharmacists, consumers, and lawyers all can be separate

identifications used to designate“reporter.”

[0020] The term“Report Type” can refer to a designation that can indicate the origin source of the report, whether it is direct or indirect submission, whether it is expedited or non-expedited, whether it contains serious or non-serious safety-related information, and the like. By way of example, the FDA defines four different“report types” as follows: 1) reports submitted directly to the FDA; 2) reports submitted by manufacturers as expedited reports (e.g., serious or unexpected adverse reactions); 3) reports submitted by manufacturers that are non-expedited reports of serious adverse events; and 4) reports submitted by manufacturers that are non- serious, non-expedited reports for new drug products.

[0021] The term“Disproportionality” can refer to a mathematical value derived from an assessment of the relative frequency of, for example, an adverse event. By way of example, disproportionality measures can be used to estimate the relative frequency of an adverse event associated with the use of a drug, vaccine, dietary supplement, or medical device. The Reporting Odds Ratio (ROR) is one example of a disproportionality measure. ROR and the related PRR disproportionality measure are commonly used by safety professionals to help identify adverse events that are reported more frequently than expected. As an example, a disproportionality measure can be generated by comparing“expected” reporting frequencies of an adverse event with the amount of that same adverse event reported for a drug, vaccine, dietary supplement, or medical device. Elevated disproportionality results indicate that there is a higher than normal reporting rate for a given adverse event.

[0022] The term“Importance Weighting” can refer to: 1) a factoring step that assigns higher weightings to safety-related reports and/or data points provided by physicians, pharmacists, and other healthcare providers when compared to weightings assigned to safety-related reports and/or data points provided by non-healthcare providers, and 2) a factoring step that assigns higher weightings to safety-related reports and/or data points where the subject of the report or data point was only taking one medical product or treatment when compared to weightings assigned to safety-related reports and/or data points where the subject of the report or data point was taking more than one medical product or treatment.

[0023] The term“Drug Schedule” can refer to a classification that delineates a level of potential harm, risk, or other safety-related consideration. By way of example, the US DEA uses schedules to classify drugs into 5 categories depending on the drug's acceptable medical use and the drug's abuse or dependency potential. The abuse rate is a determinate factor in the scheduling of the drug; for example, Schedule I drugs are considered the most dangerous class of drugs with a high potential for abuse and potentially severe psychological and/or physical dependence. As the drug schedule changes, so do the noted abuse potential and other safety- related risks.

[0024] The term“Medication Guide” can refer to a guidance document that indicates that a regulatory body, such as the US FDA, has determined that safety-related information about, for example, a drug needs to be communicated to the public. By way of example, the FDA requires that Medication Guides be issued with prescription drugs and biological products when the agency determines that 1) certain information is necessary to prevent serious adverse effects, 2) patient decision-making should be informed by information about a known serious side effect with a product, or 3) patient adherence to directions for the use of a product are essential to its effectiveness.

[0025] The term“Black box” or“Boxed warning” can refer to guidance information that indicates that a regulatory body, such as the US FDA, has determined that safety-related information about, for example, a drug needs to be communicated to the public. By way of example, the FDA assigns a boxed warning to a drug to highlight one of the following situations to prescribers: 1) there is an adverse reaction so serious in proportion to the potential benefit from the drug (e.g. fatal, life-threatening, or permanently disabling adverse reaction) that is essential that it be considered in assessing the risks and benefits of using the drug; 2) there is a serious adverse reaction that can be prevented or reduced in frequency or severity by appropriate use of the drug; or 3) FDA approved the drug with restrictions to ensure safe use because FDA concluded that the drug can be safety used only if distribution or use is restricted. There is also the case where a boxed warning can be used to highlight warning information important to the prescriber, e.g. reduced effectiveness in certain patient populations.

DETAILED DESCRIPTION

[0026] Before the various embodiments are described, it is to be understood that the teachings of this disclosure are not limited to the particular embodiments described, and as such can, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present teachings will be limited only by the appended claims.

[0027] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described in any way. While the present teachings are described in conjunction with various embodiments, it is not intended that the present teachings be limited to such embodiments. On the contrary, the present teachings encompass various alternatives, modifications, and equivalents, as will be appreciated by those of skill in the art.

[0028] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the present disclosure.

[0029] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0030] The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present claims are not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided can be different from the actual publication dates which may need to be independently confirmed.

[0031] It must be noted that as used herein and in the appended claims, the singular forms“a”, “an”, and“the” include plural referents unless the context clearly dictates otherwise. It is further noted that the claims can be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as“solely,”“only” and the like in connection with the recitation of claim elements, or use of a“negative” limitation.

[0032] As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which can be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present teachings. Any recited method can be carried out in the order of events recited or in any other order that is logically possible.

[0033] One with skill in the art will appreciate that the present disclosure is not limited in its application to the details of construction, the arrangements of components, category selections, weightings, factors, or the steps set forth in the description or drawings herein. The disclosed methods and systems are capable of other embodiments and of being practiced or being carried out in many different ways.

Overview

[0034] Provided herein is a system for estimating a level of risk associated with a given medical intervention, e.g., product or treatment. In some embodiments, a level of risk associated with a given medical intervention can comprise a score. In some embodiments, a disclosed score can comprise a safety-related score, risk score, quality score, estimation, ranking for a medical intervention, or a combination thereof. In some embodiments, a quality score can comprise a drug quality score. In some embodiments, described herein, systems may comprise: memory configured to store multiple parameters (e.g., safety-related parameters) derived from one or both pre and post-marketing safety-related information for the given medical product or treatment; and a processor coupled to the memory and operable to execute programmed instructions stored in the memory, wherein the programmed instructions are configured to: assign an individual value for one or more of various safety-related parameters, wherein the individual value or values can be based on an estimated level of risk for a patient, patient group, or population, wherein such individual value or values are summed, aggregated or combined in such a manner useful for determining a safety-related score, risk score, estimation, or ranking for the medical intervention, e.g., product or treatment. In some embodiments, a safety-related score, risk score, quality score, estimation, or ranking for a medical intervention may also be dependent on an analysis (for example, a chemical analysis) of the medical intervention. In some embodiments, a safety-related score, risk score, quality score, estimation, or ranking for a medical intervention can take into account data comprising at least in part objective chemical property data, for example, odor or taste. In some embodiments, a safety-related score, risk score, quality score, estimation, or ranking for a medical intervention can take into account data comprising at least in part chemical analysis data, or solely data from a chemical analysis. In some embodiments, a safety-related score, risk score, quality score, estimation, or ranking for a medical intervention can take into account data comprising at least in part regulatory data or solely regulatory data. In some embodiments, a safety-related score, risk score, quality score, estimation, or ranking for a medical intervention can take into account data comprising at least in part physical data unrelated to chemistry. In some embodiments, a safety-related score, risk score, quality score, estimation, or ranking for a medical intervention can take into account data comprising solely physical data unrelated to chemistry. In some embodiments, a safety-related score, risk score, quality score, estimation, or ranking for a medical intervention can take into account data comprising at least in part a combination of chemical analysis data, regulatory data, physical data unrelated to chemistry, and any combination thereof. In some embodiments, physical data unrelated to chemistry can comprise hardness, weight, density, size, shape, buoyancy, texture, color, turbidity, opacity, light reflection, dryness, hygroscopicity, static charge, conductivity, resistivity, magneticity, odor, taste, appearance, shape, mass, volume, physical dimensions, state of matter, melting point, boiling point, abnormalities of any of these, and any combination thereof.

[0035] In some embodiments, a safety-related score, risk score, quality score, estimate, or ranking for the medical intervention can comprise a safety derived score, estimate or ranking. In other words, the safety-related parameter can comprise a safety based parameter. As such, embodiments may include a system for estimating a risk score based on reported adverse events and/or chemical analysis of a medical intervention to predict outcomes associated with the use of a medical product or treatment, the system comprising: memory configured to store multiple parameters (e.g., chemical analysis and safety-related parameters) derived from one or both pre and post-marketing safety -related information for the given medical product or treatment and or a chemical analysis of a product; and a processor coupled to the memory and operable to execute programmed instructions stored in the memory, wherein the programmed instructions are configured to: assign an individual value for one or more of various safety-related parameters and/or chemical analysis result, wherein the individual value or values are based on an level of risk, patient outcome, seriousness, associated with treating a patient, patient group, or population, wherein such individual value, or values are summed, aggregated or combined in such a manner useful for determining a safety-related score, risk score, estimation, or ranking for the medical intervention, e.g., product or treatment.

[0036] In some embodiments, also provided is a method of estimating safety risks associated with the use of a medical intervention, e.g., medical product or treatment, which method includes receiving safety-related information regarding adverse events associated with a given medical intervention, (e.g., drug, medication, or medical device), the method can comprise: determining multiple parameters using such received data, the parameters being one or both of pre- and post-marketing information from various sources, assigning a predetermined estimate of the predictive value of received data with regard to a possible safety risks associated with a given medical intervention, e.g., drug, medication, or medical device), and determining a probability of the safety risks as a function of the multiple parameters.

[0037] In some embodiments, also provided is a system for estimating safety risks associated with a given medical intervention, e.g., product or treatment, which system can include a memory configured to store received data regarding the given medical intervention, e.g., drug, medication, or medical device, and a processor coupled to the memory and operable to execute programmed instructions, wherein the programmed instructions are configured to differentially weight various (a) parameters associated with each medical intervention, e.g., drug, medication, or medical device, and/or (b) chemical analysis of each medical intervention to produce a probability safety risk score or ranking as a function of such parameters.

[0038] In some embodiments, also provided is a system for estimating medical costs associated with adverse events and patient outcomes associated with a given medical intervention, e.g., product or treatment, which system can include a memory configured to store received cost data regarding the given medical intervention, e.g., drug, medication, or medical device, and a processor coupled to the memory and operable to execute programmed instructions, wherein the programmed instructions are configured to differentially weight various cost parameters associated with each medical intervention, e.g., drug, medication, or medical device, to produce a cost estimate per prescription or usage unit and determine a probability safety risk score or ranking as a function of such cost parameters. In some embodiments, an estimated cost can be based/weighted according to a chemical analysis of the medical intervention. In some embodiments, a presence of a disease causing impurity can increase a cost or a risk score associated with a medical intervention.

[0039] In some embodiments, a system for surveillance, ranking, scoring, and analyzing safety- related information can also described. In certain embodiments, the system may comprise: at least one database containing information about adverse events, or related safety information, wherein the information can include safety related information that can comprise potential risks to a patient; a first processor configured to assign pre-determined values for one or multiple risk parameters regarding an adverse event, or related safety information; a second processor configured to determine an initial risk valuation score or ranking, a third processor configured to optionally modify the initial valuation score or ranking based on user-inputted qualifiers; and a forth processor to translate the values from processor three into a final ranking or score. In some embodiments, safety related information can comprise a plurality of potential risks to a patient.

[0040] In some embodiments, a system for surveillance, ranking, scoring, and analyzing chemical analysis related information is also described. In certain embodiments, the system can comprise: at least one database containing information about adverse events and poor patient outcomes, or chemical analysis information, wherein the information includes safety-related information and can comprise a plurality of potential adverse events and poor patient outcomes associated with a result of a chemical analysis (for example, impurity, percent API, presence of contaminants, dissolution rates); a first processor configured to assign values for one or multiple adverse events or patient outcomes, or related safety information; a second processor configured to determine an initial score or ranking, a third processor configured to optionally modify the initial score or ranking based on user-inputted qualifiers; and a fourth processor to translate the values from processor three into a final ranking or score per medical intervention.

[0041] In some embodiments, a safety-related score, risk score, quality score, estimation, or ranking for a medical intervention may also take into account or be weighted based on a manufacturer’s history over a predetermined period of time, for example, less than or greater than about: 6 months, 1 year, 2 years, 3 years, 5 years, 10 years, 15 years. In some embodiments, a manufacturer’s history may comprise a safety history with regard to a particular medical intervention or group/class of medical interventions. In some embodiments, a manufacturer’s history may comprise information with regard to fines and manufacturer’s standard practices.

[0042] In some embodiments, a safety-related score, quality score risk score, estimation, or ranking for a medical intervention may be displayed or presented on a scale of a 1 -to- 100 score or a derivative thereof. In some embodiments, 1 can indicate a low risk and 100 can indicate a high risk. In some embodiments, a quality score for a medical intervention may be displayed or presented on a scale of 1 -to- 100 score. In some embodiments, 1 can indicate a low quality and high risk and 100 can indicate a high quality and low risk.

[0043] In some embodiments, a medical intervention can have a default score wherein the presence, absence, or satisfaction of a test or a criterion disclosed herein can positively impact or negatively impact a score.

[0044] In some embodiments, a medical intervention can have a default score wherein the presence, absence, or satisfaction of a test or a criterion disclosed herein can increase or decrease a score relative to a default score.

[0045] In some embodiments, a safety-related score, risk score, quality score, estimation, or ranking may be displayed or presented for specific manufacturers as an overall evaluation of the manufacturer, manufacturer’s products, or class of manufacturer’s products.

[0046] In some embodiments, a safety-related score, risk score, estimation, quality score, or ranking for a medical intervention may be displayed for each individual manufacturer of the same medical intervention and represents an evaluation of the manufacturer for that specific medical intervention only.

[0047] In some embodiments, described herein is a simple and practical procedure for the surveillance, scoring, ranking, and the like, regarding safety-related information, especially adverse event information, regarding medical interventions, e.g., drugs, vaccines, medications, dietary supplements, and medical devices.

[0048] In some embodiments, a quality score can have a maximum score and a lower limit score. In some embodiments, a maximum score can comprise about 10, about 50, about 100, about 500, or about 1000. In some embodiments, a lower score can comprise about 0. In some embodiments, a lower limit score may be a most desirable score and a maximum score may be a least desirable score. In some embodiments, a maximum limit score may be a most desirable score and a lower limit score may be a least desirable score. In some embodiments, a default score given to any medical intervention can be between a maximum score and a lower limit score. In some embodiments, negative information associated with a particular medical intervention manufactured by a particular manufacturer can increase a quality score of a medical intervention manufactured by a particular manufacturer. In some embodiments, negative information associated with a particular medical intervention manufactured by a particular manufacturer can decrease a quality score of a medical intervention manufactured by a particular manufacturer. In some embodiments, positive information associated with a particular medical intervention manufactured by a particular manufacturer can positively impact a quality score of a medical intervention manufactured by a particular manufacturer.

Factors affectins scores

[0049] In some embodiments, a score described herein can be based at least in part on one or more criterion. In some embodiments, an occurrence or severity of a criterion can increase or decrease a score by at least about 0.5%, 1%, 5%, 10%, 20, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 98%, or 99%. In some embodiments, an occurrence or severity of a criterion can weight a score by at least about 0.5%, 1%, 5%, 10%, 20, 30%, 40%, 50%, 60%, 70%, 80%,

90%, 95%, 98%, or 99%. In some embodiments, a criterion can comprise one or more of: a number of inspections on a facility producing a product, presence or absence of a recall, a number of 483 letters on a facility producing a product, a number of product complaints, a number of adverse events reported with regard to a product, a number of dosage failures, a test result, a number of failures of a test, a number of any of these over a time period, a percentage of any of these, a relative comparison of any of these to a competitor or a competitor product, and any combination thereof. In some embodiments, a time period can comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10, days, months, or years. In some embodiments, a time period can comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 months. In some cases, a number of events taking place within a time period can comprise 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 11 or more, 12 or more, 13 or more, 14 or more, or 15 or more within a time period.

[0050] In some embodiments, a criterion disclosed herein can be a result of a stakeholder feedback, including patients, providers, academic institutions, and or health systems. [0051] In some embodiments, a test can comprise one or more of: a dosage failure test, a contamination test, a drug dissolution test, a conditions test, a carcinogen levels test, a heavy metals test, and any combination thereof. In some embodiments, a drug dissolution test can comprise a United States Pharmacopoeia (USP) dissolution test. In some embodiments, a carcinogen test can comprise an FDA carcinogen levels test. In some embodiments, a microbial detection contamination test can comprise an FDA microbial contamination detection method.

In some cases, a microbial detection can comprise a PCR amplification detection method. In some embodiments, a heavy metals test can comprise an FDA heavy metals test. In some embodiments, a failure of an FDA heavy metals test can comprise a result of more than 1%, 5%, 10%, 20, 30%, 40%, 50% of FDA levels. In some embodiments, a test result disclosed herein can be outside a standard range by at least about more than 0.5%, 1%, 5%, 10%, 20, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 98%, or 99%.

[0052] In some embodiments, having no inspections (for example, by a regulatory authority) on a facility producing a product or not having an inspection on the facility for a period of time can result in a score being increased or decreased to indicate an increase risk, for example by at least 0.5%, 1%, 5%, 10%, 20, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 98%, or 99%. . In some cases, having a last inspection on a facility producing a product take place more than 10 years ago can reduce or increase a score to indicate risk that is less than if the facility was not previously inspected.. In some embodiments, having an inspection on a facility producing a product less than a period of time, for example, less than ten years ago, can result in no change to a score.

[0053] In embodiments, if a facility producing a product receives a number of letters from a regulatory authority, this can result in a change to a score. In some cases, a letter from the FDA can comprise a 483 form letter, an FDA warning letter, or a combination thereof. In some embodiments, the more warnings a facility receives from a regulatory agency, the higher the risk of a product produced by the facility. In some embodiments, a facility receiving more than five letters from a regulatory agency, for example the FDA, in 5 years can result in a score representing higher risk than a facility that received less letters in the same period of time. In some embodiments, a facility receiving more than five letters from the FDA in 5 years can result in a score decrease of 30. In some embodiments, a facility producing a product receiving no letters from a regulatory authority, for example, the FDA, can result in no change to a score or a score indicating less risk than a facility receiving one or more letters from the regulatory authority. [0054] In some embodiments, an occurrence and reporting of an adverse event can affect a score. In some embodiments, an occurrence of an adverse event can increase a risk of a product. In some embodiments, an increase in adverse effect as compared to a competitor product can result in a score representing higher risk. In some embodiments, a change in odor of a product as compared to a standard can affect a score described herein. In some embodiments, a dosage failure of a single batch can result in a score representing higher risk. In some embodiments, more batch failures can result in a higher risk as compared to less batch failures. In some embodiments, a dissolution failure can result in a score representing higher risk. In some embodiments, a dissolution test can comprise using a regulatory authority standard. In some embodiments, a dissolution test can comprise using a United States Pharmacopoeia (USP) standard. In some embodiments, a carcinogen test result failure can result in a score representing higher risk. In some embodiments, a carcinogen test can comprise using a regulatory authority standard, for example, FDA standard. In some embodiments, a heavy metals test result failure can result in a score representing higher risk. In some embodiments, a heavy metals test can comprise using a regulatory authority standard, for example, using a FDA standard. In some embodiments, detection of a microbe in a product can result in a score representing higher risk. In some embodiments, detection of a microbe in two or more batches of a product can result in a higher risk as compared to the detection of no microbe. In some embodiments, a microbial detection test can comprise using a regulatory authority standard, for example, an FDA standard.

[0055] In some embodiments, a score can be modified/affected based on manufacturing site data. For example, a location of manufactory of a product based on a continent, country, state, or city can affect a score. For example, manufacturing in the U.S., European Union, India, China, Canada, Latin America can affect a score. In some embodiments, manufactory of a product in a country or a site where products were previously removed from market, where products were sited for quality issues can result in a score indicating higher risk than products manufactured at another site.

[0056] In some embodiments, a score can be modified based on a frequency at which a criterion is recorded for batches of a medical product. In some embodiments, a criterion can comprise an event. In some embodiments, an event can comprise an adverse event. In some embodiments, a score can be based at least in part on criteria set by the FDA or another regulatory body. In some embodiments, a score can be based at least in part on physiologically relevant testing. In some embodiments, a score can be based at least in part on a percentage occurrence of an adverse event in comparison to competitors. In some embodiments, a score can comprise at least in part, modulating a quality score based on a % occurrence of an adverse event or a criterion disclosed herein in comparison to a competitors. In some embodiments, a score can at least in part be modulated based on a combination of a regulatory event and a reasonably corresponding chemical analysis or physical analysis. In some embodiments, a regulatory event can comprise occurrence of an odor change, for example, a bad odor. In some embodiments, a chemical analysis can be, for example, a detection of an presence of volatile compounds. In some embodiments a physical analysis can result in a detection of, for example, abnormal opacity or color. In some embodiments, a score can be a quality score. In some embodiments, a score can be modulated based on a combination of a chemical analysis and a reasonably corresponding physical analysis. In some embodiments, a score can be based at least in part on segregating criteria according to severity. In some embodiments, a criterion can occur while maintaining a high score, while maintaining a medium score or automatically inducing a low score. In some embodiments, a criteria may not be allowed to induce a score indicating a high risk, or a low risk. In some embodiments, scores can be segregated as high, medium, low, or a combination such as medium/low, high/medium. In some embodiments, different risk scores can be color coded. In some embodiments, a high risk score can be red, a medium risk score can be yellow, and a low risk score can be green. In some embodiments, a color coded risk score can be based on a numerically calculated risk score. In some embodiments, a color coded risk score can be a representation of a numerically calculated risk score. In some embodiments, scores can be segregated as pass/fail. In some embodiments, specific criteria can comprise dosage, dissolution, identification of inactive ingredients, presence of an impurity, presence or absence of a recall, presence of a carcinogen, heavy metals, microbial contamination detection, residual solvents, outgassing products, particulates, foreign objects, volatile compounds, cross contamination of API, or a combination thereof. In some embodiments, a criterion can comprise: dosage, dissolution, identification of inactive ingredients, presence or absence of impurity or carcinogen, presence or absence of heavy metals, microbial contamination (for example, fungal, viral, bacterial), residual solvents, outgassing products, particulates, foreign objects, volatile compounds, cross contamination of API, and any combination thereof. In some embodiments, a result of a test can have an influence on a score as shown in TABLE 1. In some embodiments, a result of a test can impact a score by decreasing or increasing a score value by 10, 30, 40, 50,

60, 70, 80, 90, or a related percentage. In some embodiments, a score of 81-100 can comprise a low risk result. In some embodiments, a score of 41-80 can comprise a medium risk result. In some embodiments, a score of 0-40 can comprise a high risk result. In some embodiments, a score of 81-100 can comprise a high risk result. In some embodiments, a score of 41-80 can comprise a medium risk result. In some embodiments, a score of 0-40 can comprise a low risk result. In some embodiments, a score can indicate a high risk or a low risk if only certain criterions are satisfied. In some embodiments, two medium risk results can result in a high risk score. In some embodiments, a single high risk result can produce an overall high risk score. In some embodiments, data from one dosage can apply to all dosages or batches of that product. In some embodiments, national drug codes (NDC) data on dosages can apply to all dosages or batches of that product. In some embodiments, a score can comprise results from a single batch, more than 33% of batches, or all batches. In some embodiments, a score can comprise a time since an event occurred. In some embodiments, the more time away from an event or criterion the higher or lower a risk score. In some embodiments, the more time away from an event or criterion the less effect the event or criterion will have on a score. In some embodiments, a score component can comprise a multiplier to score influence as shown in TABLE 2. In some embodiments, a score can comprise one or more components. In some embodiments, a multiplier can be used to modify the influence/weight of a score component based on the time since the event occurred.

[0057] TABLE 1

Score

Category Criteria Qualifiers Influence

[0058] TABLE 2

"Single Batch" failure and ">33% of batches" multipliers

[0059] In some embodiments, with regard to a quality score, the ratio of a compliant or event to all complain or event for a medical intervention can be compared to other manufacturers of the same medical intervention. In some embodiments, a ratio for a concerning complaint or serious event can be higher than the average ratio of its competitors wherein a negative score influence is triggered. In some embodiments, a ratio for a concerning complaint or serious event can be lower than the average ratio of its competitors wherein a positive score influence is triggered.

Chemical analysis [0060] In some embodiments, a score can be solely based on a chemical analysis or a chemical criteria. In some embodiments, a chemical criteria can comprise accuracy, effectiveness, parameters, presence, absence, and or evaluation of a dose, dissolution, inactive ingredient, impurity, carcinogens, heavy metals, microbial contamination, residual solvents, outgassing products, particles, foreign objects, volatile compounds, cross contamination, API, or a combination thereof. In some embodiments, the data generated from a system for estimating the safety-related severity or level of risk associated with a given medical intervention can be combined with the data from an analytical test/chemical analysis on a sample of a medical intervention. In some embodiments, a sample can comprise a whole or part of a drug or other therapeutic. In some embodiments, a sample can comprise a pill, tablet, or capsule. In some cases, the sample contains one or more ingredients. Ingredients may be active ingredients or inactive ingredients. In some instances, the active ingredients may be biologically or chemically active ingredients. In some cases, the sample is a pharmaceutical sample and contains one or more active pharmaceutical ingredients (API). The terms“active pharmaceutical ingredients” or “API” may refer to an ingredient that is biologically active. In some cases, the pharmaceutical sample contains one API. In some cases, the pharmaceutical sample contains more than one API. In some embodiments, the methods, devices, and systems provided herein are utilized to determine one or more characteristics of one or more APIs contained within a sample. Any API can be interrogated utilizing the methods, devices, and systems provided herein. Non-limiting examples of APIs suitable for interrogation with the methods, devices, and systems described herein may include; Hydrocodone/APAP (Brand Name: Vicodin®); Amoxicillin (Brand Name: Amoxil®); Lisinopril (Brand Name: Prinivil®); Esomeprazole (Brand Name: Nexium®);

Atorvastatin (Brand Name: Lipitor®); Simvastatin (Brand Name: Zocor®); Clopidogrel (Brand Name: Plavix®); Montelukast (Brand Name: Singulair®); Rosuvastatin (Brand Name:

Crestor®); Metoprolol (Brand Name: Lopressor®); Escitalopram (Brand Name: Lexapro®); Azithromycin (Brand Name: Zithromax®); Albuterol (Brand Name: ProAir® HFA);

Hydrochlorothiazide (Brand Name: HCTZ); Metformin (Brand Name: Glucophage®); Sertraline (Brand Name: Zoloft®); Ibuprofen (Brand Name: Advil®); Zolpidem (Brand Name: Ambien®); Furosemide (Brand Name: Lasix®); Omeprazole (Brand Name: Prilosec®); Trazodone (Brand Name: Desyrel®); Valsartan (Brand Name: Diovan®); Tramadol (Ultram®); Duloxetine (Brand Name: Cymbalta®); Warfarin (Brand Name: Coumadin®); Amlodipine (Brand Name: Norvasc®); Oxycodone/ APAP (Brand Name: Percocet®); Quetiapine (Brand

Name: Seroquel®); Promethazine (Brand Name: Phenergan®); Fluticasone (Brand Name: Flonase®); Alprazolam (Brand Name: Xanax®); Clonazepam (Brand Name: Klonopin®); Benazepril (Brand Name: Lotensin®); Meloxicam (Brand Name: Mobic®); Citalopram (Brand Name: Celexa®); Cephalexin (Brand Name: Keflex®); Tiotropium (Brand Name: Spiriva®); Gabapentin (Brand Name: Neurontin®); Aripiprazole (Brand Name: Abilify®);

Cyclobenzaprine (Brand Name: Flexeril®); Methylprednisolone (Brand Name: Medrol®);

Methylphenidate (Brand Name: Ritalin®); Fexofenadine (Brand Name: Allegra®); Carvedilol (Brand Name: Coreg®); Carisoprodol (Brand Name: Soma®); Digoxin (Brand Name:

Lanoxin®); Memantine (Brand Name: Namenda®); Atenolol (Brand Name: Tenormin®);

Diazepam (Brand Name: Valium®); Oxycodone (Brand Name: OxyContin®); Risedronate (Brand Name: Actonel®); Folic Acid (Brand Name: Folvite®); Olmesartan (Brand Name:

Benicar®); Prednisone (Brand Name: Deltasone®); Doxycycline (Brand Name: Vibramycin®); Alendronate (Brand Name: Fosamax®); Pantoprazole (Brand Name: Protonix®); Tamsulosin (Brand Name: Flomax®); Triamterene/HCTZ (Brand Name: Dyazide®); Paroxetine (Brand Name: Paxil®); Buprenorphine (Brand Name: Suboxone®); Enalapril (Brand Name:

Vasotec®); Lovastatin (Brand Name: Mevacor®); Pioglitazone (Brand Name: Actos®);

Pravastatin (Brand Name: Pravachol®); Fluoxetine (Brand Name: Prozac®); Insulin Detemir (Brand Name: Levemir®); Fluconazole (Brand Name: Diflucan®); Levofloxacin (Brand Name: Levaquin®); Rivaroxaban (Brand Name: Xarelto®); Celecoxib (Brand Name: Celebrex®); Codeine/ APAP (Brand Name: Tylenol® #2); Mometasone (Brand Name: Nasonex®);

Ciprofloxacin (Brand Name: Cipro®); Insulin Aspart (Novolog®); Venlafaxine (Brand Name: Effexor®); Lorazepam (Brand Name: Ativan®); Ezetimibe (Brand Name: Zetia®); Estrogen (Brand Name: Premarin®); Allopurinol (Brand Name: Zyloprim®); Penicillin (Brand Name: Pen VK®); Sitagliptin (Brand Name: Januvia®); Amitriptyline (Brand Name: Elavil®);

Clonidine (Brand Name: Catapres®); Latanoprost (Brand Name: Xalatan®); Lisdexamfetamine (Brand Name: Vyvanse®); Niacin (Brand Name: Niaspan®); Naproxen (Brand Name: Aleve®); Dexlansoprazole (Brand Name: Dexilant®); Glyburide (Brand Name: Diabeta®); Olanzapine (Brand Name: Zyprexa®); Tolterodine (Brand Name: Detrol®); Ranitidine (Brand Name:

Zantac®); Famotidine (Brand Name: Pepcid®); Diltiazem (Brand Name: Cardizem®); Insulin Glargine (Brand Name: Lantus®); Thyroid (Brand Name: Armour Thyroid®); Bupropion (Brand Name: Wellbutrin®); Cetirizine (Zyrtec®); Topiramate (Brand Name: Topamax®); Valacyclovir (Brand Name: Valtrex®); Eszopiclone (Brand Name: Lunesta®); Acyclovir (Brand Name: Zovirax®); Cefdinir (Brand Name: Omnicef®); Clindamycin (Brand Name: Cleocin®); Colchicine (Brand Name: Colcrys®); Gemfibrozil (Brand Name: Lopid®);

Guaifenesin (Brand Name: Robitussin®); Glipizide (Brand Name: Glucotrol®);

Irbesartan (Brand Name: Avapro®); Metoclopramide (Brand Name: Reglan®); Losartan (Brand Name: Cozaar®); Meclizine (Brand Name: Dramamine®); Metronidazole (Brand Name: Flagyl®); Vitamin D (Brand Name: Caltrate®); Testosterone (Brand Name: AndroGel®);

Ropinirole (Brand Name: Requip®); Olopatadine (Brand Name: Patanol®); Moxifloxacin (Brand Name: Avelox®); Enoxaparin (Brand Name: Lovenox®); Fentanyl (Brand Name:

Duragesic®); Dicyclomine (Brand Name: Bentyl®); Bisoprolol (Brand Name: Zebeta®);

Atomoxetine (Brand Name: Strattera®); Ramipril (Brand Name: Altace®); Temazepam (Brand Name: Restoril®), Phentermine (Brand Name: Adipex® P); Quinapril (Brand Name:

Accupril®); Sildenafil (Brand Name: Viagra®); Ondansetron (Brand Name: Zofran®);

Oseltamivir (Brand Name: Tamiflu®); Methotrexate (Brand Name: Rheumatrex®); Dabigatran (Brand Name: Pradaxa®); Budesonide (Brand Name: Uceris®); Doxazosin (Brand Name:

Cardura®); Desvenlafaxine (Brand Name: Pristiq®); Insulin Lispro (Brand Name: Humalog®); Clarithromycin (Brand Name: Biaxin®); Buspirone (Brand Name: Buspar®); Finasteride (Brand Name: Proscar®); Ketoconazole (Brand Name: Nizoral®); Solifenacin (Brand Name: VESIcare®); Methadone (Brand Name: Dolophine®); Minocycline (Brand Name: Minocin®); Phenazopyridine (Brand Name: Pyridium®); Spironolactone (Brand Name: Aldactone®);

Vardenafil (Brand Name: Levitra®); Clobetasol (Brand Name: Clovate®); Benzonatate (Brand Name: Tessalon®); Divalproex (Brand Name: Depakote®); Dutasteride (Brand Name:

Avodart®); Febuxostat (Brand Name: Uloric®); Lamotrigine (Brand Name: Lamictal®);

Nortriptyline (Brand Name: Pamelor®); Roflumilast (Brand Name: Daliresp®); Rabeprazole (Brand Name: Aciphex®); Etanercept (Brand Name: Enbrel®); Nebivolol (Brand Name:

Bystolic®); Nabumetone (Brand Name: Relafen®); Nifedipine (Brand Name: Procardia®); Nitrofurantoin (Brand Name: Macrobid®); Nitroglycerine (Brand Name: NitroStat® SL);

Oxybutynin (Brand Name: Ditropan®); Tadalifil (Brand Name: Cialis®); Triamcinolone (Brand Name: Kenalog®); Rivastigmine (Brand Name: Exelon®); Lansoprazole (Brand Name:

Prevacid®); Cefuroxime (Brand Name: Ceftin®); Methocarbamol (Brand Name: Robaxin®); Travoprost (Brand Name: Travatan®); Lurasidone (Brand Name: Latuda®); Terazosin (Brand Name: Hytrin®); Sumatriptan (Brand Name: Imitrex®); Raloxifene (Brand Name: Evista®); Mirtazepine (Brand Name: Remeron®); Adalimumab (Brand Name: Humira®); Benztropine (Brand Name: Cogentin®); Baclofen (Brand Name: Gablofen®); Hydralazine (Brand Name: Apresoline®); Mupirocin (Brand Name: Bactroban®); Propranolol (Brand Name: Inderal®); Varenicline (Brand Name: Chantix®); Verapamil (Brand Name: Verelan®); Clotrimazole (Brand Name: Lotrimin®); Phenytoin (Brand Name: Dilantin®); Pramipexole (Brand Name: Mirapex®); Liraglutide (Brand Name: Victoza®); Ticagrelor (Brand Name: Brilinta®);

Diclofenac (Brand Name: Voltaren®); Saxagliptin (Brand Name: Onglyza®); Lomitapide (Brand Name: Juxtapid®); Tizanidine (Brand Name: Zanaflex®); Amphetamine /Dextro amphetamine (Brand Name: Adderall®); Zoster Vaccine (Brand Name: Zostavax®);

Ezetimibe/Simvastatin (Brand Name: Vytorin®); Vilazodone (Brand Name: Vybriid®);

Hydroxyzine (Brand Name: Vistaril®); Donepezil (Brand Name: Aricept®); Acetaminophen (Brand Name: Tylenol®); and Oxcarbazepine (Brand Name: Trileptal®).

[0061] In some embodiments, the methods and systems described herein may be suitable to analyze samples containing ingredients with a molecular weight. In some cases, the molecular weight of the ingredient is 100 Daltons (Da) or less. In some cases, the molecular weight of the ingredient is equal to or less than about 150 kDa, 100 kDa, 75 kDa, 50 kDa, 25 kDa, 10 kDa, 5000 Da, 4000 Da, 3000 Da, 2000 Da, 2500 Da, 1500 Da, 1000 Da, 950 Da, 900 Da, 850 Da, 800 Da, 750 Da, 700 Da, 650 Da, 600 Da, 550 Da, 500 Da, 450 Da, 400 Da, 350 Da, 300 Da,

250 Da, 200 Da, 150 Da, 100 Da, 95 Da, 90 Da, 85 Da, 80 Da, 75 Da, 70 Da, 65 Da, 60 Da, 55 Da, 50 Da, 45 Da, 40 Da, 35 Da, 30 Da, 25 Da, 20 Da, 15 Da, 10 Da, 5 Da. In some cases, the active ingredient is a protein or peptide. In some cases, the active ingredient is a small molecule or a small molecular compound.

[0062] In some embodiments, the pharmaceutical sample may contain one or more

excipients. An excipient may be an inactive ingredient that is biologically inert. In some cases, the methods, devices, and systems described herein are capable of distinguishing between the ingredient (e.g., an API) and the one or more excipients. In some cases, the one or more excipients are filtered or otherwise removed from the sample prior to analysis. In some cases, the methods provide for filtering at least a portion of the one or more excipients from the sample prior to analysis. Excipients may include, for example, emulsifiers, stabilizers, suspending agents, binders, viscosity -increasing agents, disintegrants, antiseptics, antimicrobial agents, preservatives, disinfectants, solvents, antioxidants, diluents, sugar coatings, sweeteners, adsorbents, anticaking agents, glidants, emulsion stabilizers, thermal stabilizers, water-absorbing agents, lubricants, chelators, film-formers, granulating agents, extended release agents, stiffening agents, cationic surfactants, non-ionic surfactants, anionic surfactants, detergents, wetting agents, reducing agents, buffering agents, nutrients, dietary supplements, clouding agents, anti-foaming agents, emollients, colorants, coating agents, flavoring fixatives, fillers, gelling agents, humectants, plasticizers, tonicity agents, stabilizing agents, thickening agents, rate-controlling polymers, lyophilization aids, bulking agents, dissolution aids, ointment bases, suppository bases, water-miscible cosolvents, mucoadhesives, dispersing agents, coemulsifying agents, alkalizing agents, acidifying agents, skin penetrants, carbonating agents, sequestering agents, opacifiers, and pigments. Non-limiting examples of excipients may include acacia, alginate, alginic acid, aluminum acetate, benzyl alcohol, butyl paraben, butylated hydroxy toluene, citric acid, calcium carbonate, candelilla wax, croscarmellose sodium, confectioner sugar, colloidal silicone dioxide, cellulose, plain or anhydrous calcium phosphate, camuba wax, corn starch, carboxymethylcellulose calcium, calcium stearate, calcium disodium EDTA, copolyvidone, castor oil hydrogenated, calcium hydrogen phosphate dehydrate, cetylpyridine chloride, cysteine HCL, crosspovidone, dibasic calcium phosphate, disodium hydrogen phosphate, dimethicone, erythrosine sodium, ethyl cellulose, gelatin, glyceryl monooleate, glycerin, glycine, glyceryl monostearate, glyceryl behenate, hydroxy propyl cellulose, hydroxyl propyl methyl cellulose, hypromellose, HPMC phthalate, iron oxides or ferric oxide, iron oxide yellow, iron oxide red or ferric oxide, lactose hydrous or anhydrous or monohydrate or spray dried, magnesium stearate, microcrystalline cellulose, mannitol, methyl cellulose, magnesium carbonate, mineral oil, methacrylic acid copolymer, magnesium oxide, methyl paraben, povidone or polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polysorbate 80, propylene glycol, polyethylene oxide, propylene paraben, polaxamer 407 or 188 or plain, potassium bicarbonate, potassium sorbate, potato starch, phosphoric acid, polyoxyl40 stearate, sodium starch glycolate, starch pregelatinized, sodium crossmellose, sodium lauryl sulfate, starch, silicon dioxide, sodium benzoate, stearic acid, sucrose, sorbic acid, sodium carbonate, saccharin sodium, sodium alginate, silica gel, sorbiton monooleate, sodium stearyl fumarate, sodium chloride, sodium metabi sulfite, sodium citrate dehydrate, sodium starch, sodium carboxy methyl cellulose, succinic acid, sodium propionate, titanium dioxide, talc, triacetin, and triethyl citrate.

[0063] A medical intervention may additionally contain one or more impurities. An impurity may be, for example, formed during the manufacturing process such as unreacted starting material or intermediates or byproducts. Impurities may include degradation products such as those formed during the synthetic process, during storage, during formulation of the dosage form or during aging of the drug. Additional impurities may include inorganic impurities,

stereoisomeric impurities, structural isomer impurities, reagents, ligands, catalysts, heavy metals, filter aids, charcoal, and residual solvents. In some cases, the impurities are formulation- related impurities such as method related, environmental related (e.g., exposure to adverse temperatures, light (e.g., U. V.), or humidity), and dosage form related such as mutual interaction amongst ingredients, and functional group related degradation (e.g., ester hydrolysis, hydrolysis, oxidative degradation, photolytic cleavage, or decarboxylation). In some cases, the methods, devices, and systems described herein are capable of distinguishing between an API and one or more impurities contained in the sample. In some embodiments, a safety related score is based/weighted based on the presence, absence or quantity of one or more impurities in a medical intervention.

[0064] In some embodiments, an analytical test on a sample can be performed to determine impurities, irregularities, or other differences between batches of drugs or other therapeutics. In some instances, an analytical test can be performed using a nuclear magnetic resonance spectroscopy, mass spectroscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, immunoassays, enzyme immunoassays, enzyme-multiplied immunoassay technique (EMIT), fluorescence polarization immunoassay (FPIA), radio immunoassay (RIA), kinetic interaction of microparticles in solution (KIMS), cloned enzyme donor immunoassay (CEDIA), rapid slide tests (point-of-care testing), a chromatographic testing method, thin-layer chromatography (TLC), liquid chromatography (HPLC), gas chromatography (GC), or any combination thereof. In some embodiments, an analytical test is performed using Raman spectroscopy. Techniques disclosed herein may be performed by any known analytical tests (e.g., by performing a plurality of analytical tests for a plurality of quality metrics). Non-limiting examples of techniques (analytical test) for identifying chemicals and verifying the integrity of pharmaceutical products may include, for example, nuclear magnetic resonance spectroscopy (NMR), mass spectroscopy (MS), Fourier transform infrared spectroscopy, Raman spectroscopy, immunoassays, enzyme immunoassays, enzyme-multiplied immunoassay technique (EMIT), fluorescence polarization immunoassay (FPIA), radio immunoassay (RIA), kinetic interaction of microparticles in solution (KIMS), cloned enzyme donor immunoassay (CEDIA), rapid slide tests (point-of-care testing), a chromatographic testing method, thin-layer chromatography (TLC), liquid

chromatography (HPLC), gas chromatography (GC), or any combination thereof.

Drug variability

[0065] Existing medical interventions, (e.g., drugs, consumables, or medications) may have variability, e.g., in active ingredients such as active pharmaceutical ingredients. In some embodiments, a safety related score is based/weighted based on such variability. For example, the presence of a carcinogenic impurity would increase a risk score as compare to a presence of a benign impurity. In some instances, counterfeit consumables or medications may exist such that the medications are ineffective, less effective than indicated, or even harmful (containing disease causing agents). The present disclosure provides methods for analyzing medications or drugs to assess risk of use. In some instances, medical interventions may be chemically validated and analyzed. Alternatively or in addition, medical interventions may be optically validated and analyzed. In some instances, the medications may be validated or verified with a laser-based system (e.g., spectroscopy or Raman spectroscopy) or a method disclosed herein. In addition, wet-lab and software innovations may be integrated. Medical interventions may be validated or analyzed (e.g., for dosage analysis) with an error less than 0.1%, 0.2%, 0.5%, 1%, 2%, 5%, 10%, 15%, or 20%. Medical interventions may be validated or analyzed (e.g., for dosage analysis) to ensure that variability in dosage or weight is no more than 0.1%, 0.2%,

0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, or 20%. Such cutoffs for acceptable variability may be pharmacologically established for each different medication. For example, narrow-index therapeutic drugs may have relatively lower variability cutoffs (e.g., no more than 0.1%, 0.2%, 0.5%, 1%, 2%, 3%, 4%, or 5%) because of a lower tolerance for dose variation (e.g., warfarin). As another example, wider-index therapeutic drugs may have relatively higher variability cutoffs because a wider range of dose may be acceptable (e.g., acetaminophen). Variability cutoffs for each drug may also be established based in part on a regulatory cutoff for allowed variability. Medical interventions may be validated or analyzed quickly, such as in less than a week, less than 3 days, less than a day, less than 16 hours, less than 8 hours, less than 4 hours, less than 2 hours, less than an hour, less than 30 minutes, less than 15 minutes, less than 5 minutes, less than 2 minutes, less than a minute, or any amount of time there between. The validation or analysis of the medical interventions may comply with ISO 17025 standards. The validation or analysis of the medical intervention may comply with USP <905> standards as to content and uniformity, such that if a tested batch or subset of a batch of medication is measured to fall outside of the bounds indicated by the standards, then it is marked as failing the validation test, rejected for human consumption, and assigned a risk score or related value. Alternatively, or in addition, in some aspects, the validation standards can be more stringent than USP <905> and/or other FDA standards. In some aspects, if a tested batch or subset of a batch of medical interventions is measured to fall within the bounds indicated by the standards, then it is marked as validated and is assigned a predetermined value.

[0066] In some embodiments, medical interventions comprising an allegedly same active ingredient may vary, in some cases substantially, from one another. In some instances, medications may comprise an incorrect amount of the ingredient of interest or incorrect types of inactive ingredients such as fillers. The variability may in some instances lead to harm to a user of the medication. For example, taking medication may lead to seizures or adverse effects due to the incorrect amount of the active ingredient and/or inclusion of wrong fillers. For example, case studies of anti-epileptic drugs (AEDs) have shown a link between breakthrough seizures and generic AED substitution, and that AED prescription filling itself was associated with a 2.3- fold elevated odds of seizure-related events. In some embodiments, a validated medical intervention is according to manufacturer or a regulatory agency specification. In some embodiments, a medical intervention outside manufacturer or a regulatory agency specification adversely affects a risk score (increases a risk score).

Accuracy

[0067] In some cases, the methods and systems provide for accuracy in determining the presence or absence of a property described herein, for example, an impurity, contaminant, dissolution rate, or an API. Accuracy is a measurement of how closely a value conforms to the correct value. In some cases, the methods, devices, and systems analyze the quantity or purity of an ingredient in the sample with an accuracy of about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%, about 4.6%, about 4.7%, about 4.8%, about 4.9%, about 5.0%, about 5.1%, about 5.2%, about 5.3%, about 5.4%, about 5.5%, about 5.6%, about 5.7%, about 5.8%, about 5.9%, about 6.0%, about 6.1%, about 6.2%, about 6.3%, about 6.4%, about 6.5%, about 6.6%, about 6.7%, about 6.8%, about 6.9%, about 7.0%, about 7.1%, about 7.2%, about 7.3%, about 7.4%, about 7.5%, about 7.6%, about 7.7%, about 7.8%, about 7.9%, about 8.0%, about 8.1%, about 8.2%, about 8.3%, about 8.4%, about 8.5%, about 8.6%, about 8.7%, about 8.8%, about 8.9%, about 9.0%, about 9.1%, about 9.2%, about 9.3%, about 9.4%, about 9.5%, about 9.6%, about 9.7%, about 9.8%, about 9.9%, about 10.0%, or greater than 10.0%.

[0068] In some cases, the methods and systems determine the amount of an ingredient (e.g., an API) in the sample with an error rate equal to or less than about 10%, 9.9%, 9.8%, 9.7%, 9.6%, 9.5%, 9.4% 9.3%, 9.2%, 9.1%, 9.0%, 8.9%, 8.8%, 8.7%, 8.6%, 8.5%, 8.4%, 8.3%, 8.2%, 8.1%, 8.0%, 7.9%, 7.8%, 7.7%, 7.6%, 7.5%, 7.4%, 7.3%, 7.2%, 7.1%, 7.0%, 6.9%, 6.8%, 6.7%, 6.6%,

6.5%, 6.4%, 6.3%, 6.2%, 6.1%, 6.0%, 5.9%, 5.8%, 5.7%, 5.6%, 5.5%, 5.4%, 5.3%, 5.2%, 5.1%,

5.0%, 4.9%, 4.8%, 4.7%, 4.6%, 4.5%, 4.4%, 4.3%, 4.2%, 4.1%, 4.0%, 3.9%, 3.8%, 3.7%, 3.6%,

3.5%, 3.4%, 3.3%, 3.2%, 3.1%, 3.0%, 2.9%, 2.8%, 2.7%, 2.6%, 2.5%, 2.4%, 2.3%, 2.2%, 2.1%,

2.0%, 1.9%, 1.8%, 1.7%, 1.6%, 1.5%, 1.4%, 1.3%, 1.2%, 1.1%, 1.0%, 0.9%, 0.8%, 0.7%, 0.6%,

0.5%, 0.4%, 0.3%, 0.2%, 0.1%, or less. [0069] In some cases, the methods and systems provide for improved precision. Precision may refer to the closeness of two or more measurements and may reflect the amount of variability in the system. In some cases, the methods, devices, and systems analyze the quantity of an ingredient in the sample with a precision equal to or less than about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%, about 4.6%, about 4.7%, about 4.8%, about 4.9%, about 5.0%, about 5.1%, about 5.2%, about 5.3%, about 5.4%, about 5.5%, about 5.6%, about 5.7%, about 5.8%, about 5.9%, about 6.0%, about 6.1%, about 6.2%, about 6.3%, about 6.4%, about 6.5%, about 6.6%, about 6.7%, about 6.8%, about 6.9%, about 7.0%, about 7.1%, about 7.2%, about 7.3%, about 7.4%, about 7.5%, about 7.6%, about 7.7%, about 7.8%, about 7.9%, about 8.0%, about 8.1%, about 8.2%, about 8.3%, about 8.4%, about 8.5%, about 8.6%, about 8.7%, about 8.8%, about 8.9%, about 9.0%, about 9.1%, about 9.2%, about 9.3%, about 9.4%, about 9.5%, about 9.6%, about 9.7%, about 9.8%, about 9.9%, about 10.0%, or greater than 10.0%.

[0070] In some aspects, the methods, and systems may distinguish between an impurity and an active ingredient in a sample. In some cases, the methods and devices may be capable of detecting an impurity in a sample containing the impurity and an active ingredient. In some cases, the methods and devices are capable of detecting an impurity in a sample that contains about 0.05%, 0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, or greater than 99% of the impurity.

Computer Systems

[0071] Provided herein are a variety of computer systems and methods that can be implemented on a computer. In certain embodiments, a general-purpose computer can be configured to a functional arrangement for the methods and programs disclosed herein. The hardware architecture of such a computer is well known by a person skilled in the art, and can comprise hardware components including one or more processors (CPU), a random-access memory (RAM), a read-only memory (ROM), an internal or external data storage medium (e.g., hard disk drive, flash memory, TCP/IP layer data stream etc.). A computer system can also comprise one or more graphic boards for processing and outputting graphical information to display means. The above components can be suitably interconnected via a bus inside the computer. The computer can further comprise suitable interfaces for communicating with general-purpose external components such as a monitor, keyboard, mouse, network, storage media etc. In some embodiments, the computer can be capable of parallel processing or can be part of a network configured for parallel or distributive computing to increase the processing power for the present methods and programs. In some embodiments, the program code read out from the storage medium can be written into a memory provided in an expanded board inserted in the computer, or an expanded unit connected to the computer, and a CPU or the like provided in the expanded board or expanded unit can actually perform a part or all of the operations according to the instructions of the program code, so as to accomplish the functions described below. In other embodiments, the method can be performed using a cloud computing system. In these embodiments, the data files and the programming can be exported to a cloud or distributed computer system, which runs the program, and returns an output to the user.

[0072] A system can in certain embodiments comprise a computer that includes: a) a central processing unit; b) a main non-volatile storage drive, which can include one or more hard drives, for storing software and data, where the storage drive is controlled by disk controller; c) a system memory, e.g., high speed random-access memory (RAM), for storing system control programs, data, and application programs, including programs and data loaded from non-volatile storage drive; d) system memory can also include read-only memory (ROM); flash memory, a user interface, including one or more input or output devices, such as a mouse, a keypad, and a display; e) an optional network interface card for connecting to any wired or wireless communication network, e.g., a printer; and f) an internal bus for interconnecting the

aforementioned elements of the system.

[0073] The memory of a computer system can be any device that can store information for retrieval by a processor, and can include magnetic or optical devices, or solid-state memory devices (such as volatile or non-volatile RAM or ROM), where in some instances the memory is present on or part of a non-transitory physical medium. A memory or memory unit can have more than one physical memory device of the same or different types (for example, a memory can have multiple memory devices such as multiple drives, cards, ICs, or multiple solid state memory devices or some combination of the same). With respect to computer readable media, "permanent memory" refers to memory that is permanent. Permanent memory is not erased by termination of the electrical supply to a computer or processor. Computer hard-drive ROM (i.e., ROM not used as virtual memory), CD-ROM, floppy disk, flash memory, Blue ray, and DVD are all examples of permanent memory. Random Access Memory (RAM) is an example of non permanent (i.e., volatile) memory. A file in permanent memory can be editable and re-writable.

[0074] In some embodiments, operation of a computer can be controlled primarily by an operating system, which is executed by a central processing unit. The operating system can be stored in a system memory. In some embodiments, the operating system can include a file system. In addition to an operating system, one possible implementation of the system memory includes a variety of programming files and data files for implementing the method described below. In certain cases, the programming can contain a program, where the program can be composed of various modules, and a user interface module that permits a user at a user interface to manually select or change the inputs to or the parameters used the programming. The data files can include various inputs for the programming.

[0075] In certain embodiments, instructions in accordance with the method described herein can be coded onto a computer-readable medium in the form of "programming," where the term "computer readable medium" as used herein refers to any storage or transmission medium that participates in providing instructions and/or data to a computer for execution and/or processing. Examples of storage media include a floppy disk, hard disk, optical disk, magneto-optical disk, CD-ROM, CD-R, magnetic tape, non-volatile memory card, ROM, RAM, flash memory, DVD- ROM, Blue-ray disk, solid state disk, TCP/IP, TCP and UDP data streams at all layers, and network attached storage (NAS), whether or not such devices are internal or external to the computer or storage is volatile or non-volatile. Information can be stored on computer readable medium.

[0076] The computer-implemented method described herein can be executed using

programming that can be written in one or more of any number of computer programming languages. Such languages include, for example, C (Bell Labs), Java (Sun Microsystems, Inc., Santa Clara, Calif.), Visual Basic (Microsoft Corp., Redmond, Wash.), Python (Python Software Foundation), and C++ (AT&T Corp., Bedminster, N.J.), as well as any many others.

[0077] In any embodiment, data can be forwarded to a“remote location,” where“remote location,” refers to a location other than the location at which the program is executed. For example, a remote location could be another location (e.g., office, lab, etc.) in the same city, another location in a different city, another location in a different state, another location in a different country, etc. As such, when one item is indicated as being“remote” from another, what is meant is that the two items can be in the same room but separated, or at least in different rooms or different buildings, and can be at least one mile, ten miles, or at least one hundred miles apart.“Communication” information references transmitting the data representing that information as electrical signals over a suitable communication channel (e.g., a private or public network).“Forwarding” an item refers to any means of getting that item from one location to the next, whether by physically transporting that item or otherwise (where that is possible) and includes, at least in the case of data, physically transporting a medium carrying the data or communicating the data. Examples of communicating media include radio or infra-red transmission channels as well as a network connection to another computer or networked device, and the internet or including email transmissions and information recorded on websites and the like.

[0078] In some embodiments, method and system can be based on compiling and weighting various costing data regarding AE and patient outcomes with data from a post-marketing safety database for generating a surveillance indicator, a score, and/or a rank regarding the safety of a drug, vaccine, medication, dietary supplement, or medical device.

[0079] Other embodiments of the disclosure may include a method and system based on compiling and weighting various safety-related components, chemical analysis, data points, warnings, and related safety-related information with, optionally, existing rankings, for generating a surveillance indicator, a score, and/or a rank regarding the safety of a drug, vaccine, medication, dietary supplement, or medical device.

[0080] Some embodiments include implementation on a single computer, or across a network of computers, or across networks of networks of computers, for example, across a network cloud, across a local area network, on hand-held computer devices, etc. Some embodiments include implementation on computer program(s) performing one or more of the steps described herein. Such computer programs execute one or more of the steps described herein. Some embodiments of the disclosure include various data structures, categories, and modifiers described herein, encoded on computer-readable medium(s) and transmissible over communications network(s).

[0081] Software, web, Internet, "cloud," or other storage and computer network

implementations of the present disclosure could be accomplished with standard programming techniques to accomplish the various database searching, modifying, correlating, comparing, deciding, scoring, surveillance, and ranking steps.

Reporting Database

[0082] Certain embodiments described herein relate to a computer-assisted method of processing multiple drug, vaccine, medication, dietary supplement, and medical device information sources. [0083] The system may use a variety of safety-related information sources available at the time of forecast to determine the risk(s) associated with the use of a drug, vaccine, medication, dietary supplement, and medical device. The available information may include, for example, patient outcomes taken, for example, from the Agency for Healthcare Regulation and Quality's (AHRQ) Healthcare Cost and Utilization Project (HCUP), National Health Expenditure

Accounts (NHEA, which are produced annually by the Centers for Medicare & Medicaid Services (CMS)), National (Nationwide) Inpatient Sample (NIS), Kids' Inpatient Database (KID), Nationwide Emergency Department Sample (NEDS), and the like, or from state-specific databases such as State Inpatient Databases (SID), State Ambulatory Surgery and Services Databases (SASD), State Emergency Department Databases (SEDD), and similar national or state-specific databases in the US and their worldwide (i.e., non-United States national and/or provisional/state) counterparts, and AE and patient outcome data taken from, for example, FAERS data, or similar US or worldwide post-marketing databases, claims data, or clinical trial data. The available information may also include, for example, a multiple category matrix that differentially weighs various potential harm indicators, for example, FDA FAERS categories of: Outcome, Adverse Event Seriousness, Condition Seriousness, Event Reporter, and Report Type), or similar national or global counterparts with, optionally, existing FDA and US Drug and Enforcement Agency (DEA) guidance, or similar national or global counterparts. Additional weightings and modifiers can include a disproportionality measure, an event reporter “Importance Weighting,” and a comorbidity factor, or similar national or global counterparts in this specific example. Other optional steps include additional statistics processing and ranking, scoring, or indicating with product classes or designations. In some embodiments, the system can use a mathematical model to determine one or more parameters using the available information.

Exemplary Embodiments

[0084] In some embodiments, the figures illustrate exemplary embodiments in detail a method and system for evaluating risks associated with the use of a medical intervention, e.g., drug, vaccine, medication, dietary supplement, and medical device, are disclosed.

[0085] As a non-limiting example, one skilled in the art could practice such embodiments by using different, from the illustrative example below, safety-related information, safety -related information sources, weightings, categories, modifiers, inclusions, exclusions, percentages, percentiles, words, or letters, for example. Some embodiments described herein relate to systems and methods for automating the estimation of safety-related severity or level of risk associated with the use of drugs, vaccines, medications, dietary supplements, and medical devices by integrating information from multiple databases and creating decision making advice useful to patients, healthcare providers, drug developers, investors, insurance providers, legal analysts, researchers, and policy makers.

[0086] One system calculates the safety-related severity or level of risk associated with the use of a drug, vaccine, medication, dietary supplement, or medical device for a subject by combining cost-related data, such as adverse event medical cost data, patient outcome medical cost data, and/or similar cost information, with AE and patient outcome data from adverse event databases such as FAERS and related global data counterparts. In some embodiments, an assessment for example a safety-related severity or level of risk associated with the use of a drug, vaccine, medication, dietary supplement, or medical device can be further based on a chemical analysis.

[0087] In some instances, the system also calculates the safety-related severity or level of risk associated with the use of a drug, vaccine, medication, dietary supplement, or medical device for a subject from safety-related data, such as condition data, adverse event seriousness data, disproportionality measures, event reporter "Importance Weighting," and comorbidity data, and/or similar national or global counterparts, with optional information on addiction potential, FDA waming(s), DEA waming(s), and/or similar national or global counterparts etc.

[0088] A method of estimating the safety-related severity or level of risk associated with the use of drugs, vaccines, medications, dietary supplements, and medical devices includes receiving safety-related data, such as condition data, adverse event seriousness data, disproportionality measures, and comorbidity data, and/or similar national or global counterparts, with optional information on addiction potential(s), government warnings and designations, various sub designations found in adverse event reporting systems, and/or similar national or global counterparts, etc. associated with a given drug, vaccine, medication, dietary supplement, or medical device; optionally applying an event reporter "Importance Weighting" factor;

determining multiple parameters using such received data, assigning an estimate of the predictive value of received data with regard to a possible safety risk associated with a given drug, vaccine, medication, dietary supplement, or medical device, and generating a score, ranking, or other designation regarding potential safety-related risks as a function of multiple parameters or a weighting of the multiple parameters.

[0089] In some embodiments, a system for estimating safety-related severity or level of risk associated with a given drug, vaccine, medication, dietary supplement, or medical device includes memory configured to store received data regarding the given drug, vaccine, medication, dietary supplement, or medical device and a processor coupled to the memory and operable to execute programmed instructions, wherein the programmed instructions are configured to weigh various safety -related parameters associated with a drug, vaccine, medication, dietary supplement, or medical device to produce a safety risk score, ranking, designation, or estimate as a function of such parameters.

[0090] Certain embodiments of the present disclosure relate to the monitoring of safety-related severity, or level of risk associated with a given drug, vaccine, medication, dietary supplement, or medical device. More particularly, embodiments of the present disclosure relate to methods and systems that integrate information derived from multiple safety -related databases and differentially weight and/or value such information to create safety -related information output useful to healthcare providers, insurers, managed care administrators, patients, analysts, and policy makers.

[0091] Certain embodiments of the present disclosure relate generally to systems and methods for processing information regarding safety-related severity, and patient outcomes, health consequences, or level of risk associated with a given drug, vaccine, medication, dietary supplement, or medical device. More specifically, it relates to extracting safety -related severity, chemical analysis data, or level of risk data from drug, vaccine, medication, dietary supplement, and medical device information sources in a manner to support use of the data with analytic tools, scorings, and rankings.

[0092] In certain embodiments, the methods and systems comprise an automated name matching system that: i) corrects for drug, vaccine, dietary supplement, or medical devices name misspellings and incorrect data within the major fields (i.e., the inclusion of dosages or routes of administration as part of the drug name field); ii) aggregates generic and non-U. S. names under a single U.S. brand name; iii) removes duplicate case reports; and iv) identifies common adverse event and condition types within the database. Once these data cleaning steps are completed the data is used to calculate the safety scoring or ranking system disclosed herein. One version of the scoring and ranking system can comprise a multi-category matrix that differentially weighs various potential harm indicators. For example, in one version of the system, a drug safety scoring and ranking was created by combining the output of FDA FAERS case reports regarding prescription drugs with, optionally, existing FDA and Drug and Enforcement Agency (DEA) guidance, and the chemical analysis of drug samples.

[0093] As an example, the score and ranking calculation may incorporate downstream medical costs based on AE and outcome costing data taken from the Agency for Healthcare Regulation and Quality's (AHRQ) Healthcare Cost and Utilization Project (HCUP), National Health Expenditure Accounts (NHEA) or other similar sources such as the National (Nationwide) Inpatient Sample (NIS), Kids' Inpatient Database (KID), Nationwide Emergency Department Sample (NEDS), and the like, or from state-specific databases such as State Inpatient Databases (SID), State Ambulatory Surgery and Services Databases (SASD), State Emergency Department Databases (SEDD), and the like, and map such costs to adverse event and outcome case report data derived from FAERS, or other similar safety databases, in order to calculate a cost per drug, vaccine, medication, dietary supplement, or medical device or cost per unit exposure to a given drug, vaccine, medication, dietary supplement, or medical device, and optionally present such cost figures and rankings as a simple 1 -to- 100 score.

[0094] In some instances, the score and ranking calculation may further incorporate a number of FAERS post-marketing adverse event datasets for each scored drug including:“Out-come,” "Adverse Event Seriousness," "Condition Serious-ness," "Event Reporter," and "Report Type." To account for a given subject's existing comorbidity burden we used the van-Walraven

Elixhauser index (a measurement system regarding a patient's pre-existing medical conditions) to negatively adjust the "Outcome" portion of the score. An optional event reporter "Importance Weighting" was used to adjust the weighting of individual case reports. A final FAERS-related category was the inclusion of a disproportionality measure, the Reporting Odds Ratio (ROR), regarding specific adverse events linked to a given drug. These datasets were then, optionally, combined and weighted with FDA "medication guides," FDA "boxed warnings," and DEA drug schedule classifications regarding abuse potential. The output of the matrix calculation for each drug was then presented on a simple 1 -to- 100 score.

[0095] In another example, the score and ranking calculation may further incorporate a number of FAERS post-marketing adverse event datasets for each scored drug including: "Outcome,” “Adverse Event Seriousness,”“Condition Seriousness,” and“Report Type.” The“Event Reporter” field may be given an“Importance Weighting” to account for an assumed increase in reporting accuracy by healthcare professionals versus non-healthcare professionals. To account for a given subject's existing comorbidity burden the van-Walraven Elixhauser index (a measurement system regarding a patient's pre-existing medical conditions) may be used to negatively adjust the“Outcome” portion of the score. A final FAERS -related category may be the inclusion of a disproportionality measure, the Reporting Odds Ratio (ROR), regarding specific adverse events linked to a given drug. The output of the matrix calculation for each drug may then presented on a simple 1 -to- 100 score, where desired.

[0096] In yet another example, the score and ranking calculation may further incorporate a number of FAERS post-marketing adverse event datasets for each scored drug including: "Outcome," "Adverse Event Seriousness," "Condition Seriousness," and "Report Type." The "Event Reporter" field may be modified by an "Importance Weighting" in order to 1) assign higher weightings to safety-related reports and/or data points provided by physicians, pharmacists, and other healthcare providers when compared to weightings assigned to safety- related reports and/or data points provided by non-healthcare providers, and 2) assign higher weightings to safety-related reports and/or data points where the subject of the report or data point was only taking one medical product or treatment when compared to weightings assigned to safety -related reports and/or data points where the subject of the report or data point was taking more than one medical product or treatment.

[0097] In some embodiments, pre-existing disease, disorder, or condition a subject is suffering from is reported in the "Adverse Event" field of a case report. To account for this, an automated system according to embodiments of the disclosure may be configured to omit such instances where a pre-existing disease, disorder, or condition is listed in the "Adverse Events" field from the scoring and ranking analysis. To account for a given subject's existing comorbidity burden, the van-Walraven Elixhauser index (a measurement system regarding a patient's pre-existing medical conditions) may be employed to negatively adjust the "Outcome" portion of the score.

A final category may be the inclusion of a disproportionality measure, the Reporting Odds Ratio (ROR), regarding specific adverse events linked to a given drug. The output of the matrix calculation for each drug may then be presented on a simple 1 -to- 100 score, where desired.

[0098] While the surveillance, scoring, and ranking systems detailed herein employ mainly post marketing safety information, one skilled in the art could contemplate integrating data and information taken from numerous pre-marketing sources such as clinical trial results, label insert information, scientific literature, anecdotal reports, proceedings from scientific conferences, government reports, information from compilations such as the "Physicians' Desk Reference," etc., as well as integrating data and information taken from other post- or pre-marketing sources.

[0099] In evaluating the potential risk associated with a given drug, vaccine, dietary supplement, medication or medical device, one may use a mathematical model to perform calculations that include one or more safety-related parameters related to the probability of an adverse event, side effect, or safety-related consequence being associated with a given drug, medication, vaccine, dietary supplement, or medical device.

[0100] For example, determining the safety risk or ranking of a drug, vaccine, medication, dietary supplement or medical device may involve simultaneous assessment of several safety- related parameters, which can be connected by a matrix of adverse event, side effect, or safety- related consequences and/or probabilities of such consequences. Choosing these parameters, and how to weigh their individual contribution within a mathematical model may vary, as desired. Various permutations of such parameters, weights, and contributions to the scoring, or ranking may be employed, as desired.

[0101] Some embodiments relate to systems and methods for automating and simplifying adverse event, and other safety-related, information regarding drugs, vaccines, dietary supplements, and medical devices by integrating information from multiple safety-related databases and creating decision supporting advice, rankings, estimations, and scorings useful to patients, healthcare providers, drug developers, investors, researchers, analysts, manage care administrators, insurance providers, policy makers, and the like.

[0102] In some embodiments, a system for analyzing safety-related information associated with adverse events and patient outcomes including a client, a database, and a server. The client allows chemical analysis information regarding adverse events, patient outcomes, or other safety -related information a drug, obtained from one or more sources to be entered into the system and a ranking, scoring, classification, or other safety-related endpoint to be returned from the system. The client also allows information regarding adverse events, patient outcomes, or other safety -related information, obtained from one or more adverse event-related sources to be entered into the system and mapped to the ranking safety-related information returned from the system. In some embodiments, the chemical analysis data and adverse event database data is combined to produce a score per drug, vaccine, dietary supplement, or medical device or combined to produce a score per unit exposure to a drug, vaccine, dietary supplement, or medical device.

[0103] In some embodiments, the server obtains chemical analysis information entered through the client, maps each chemical analysis information to safety-related adverse event and outcome data from safety databases such as FAERS, translates the chemical analysis information and corresponding adverse event and outcome data into a numerical value, and returns a risk ranking, or score to the client. The risk calculated by the server and returned to the client may be a score, a rank, a classification or any combination of one or all. This embodiment may further include one or more modifiers entered into the system through the client that is used by the server to modify the risk determined by the server and returned to the client.

[0104] Another embodiment is a system for analyzing safety-related information including a client, a database, and a server. The client allows information regarding adverse events, or other safety-related information, obtained from one or more safety-related databases to be entered into the system and a ranking, scoring, classification, or other safety-related endpoint to be returned from the system. The database contains information from various safety-related databases as well as other information on drugs, vaccines, dietary supplements, and medical devices.

[0105] In some embodiments, a server obtains safety-related information entered through the client, calculates a weighting for each safety-related risk contained in the information entered through the client, translates the weightings into a numerical value, and returns a risk ranking, or score to the client. The risk calculated by the server and returned to the client may be a score, a rank, a classification or any combination of one or all. This embodiment may further include one or more modifiers entered into the system through the client that is used by the server to modify the risk determined by the server and returned to the client.

[0106] Another embodiment is a method for calculating an overall score or ranking risk for a patient by scoring or ranking a member, select members, or all members of the drugs, vaccines, medications, dietary supplements, or medical devices the patient may be using. This method has several steps, although it will be appreciated that two or more of the following steps could be collapsed into a single step, or one or more of these steps may be broken up into even more steps, or one or more of these steps may be omitted for a given analysis. In a first step, a list of drugs, vaccines, medications, dietary supplements, or medical devices for patient is obtained. In a second step, a list of comorbidities, if any, of the patient is obtained. In a third step, individual risk scores or ranking are calculated for each of the list of drugs, vaccines, medications, dietary supplements, or medical devices that the patient is using. In a fourth step, a combined, or total, risk score or ranking regarding the patient is calculated from individual risk scores or rankings obtained for that patient. In a fifth step, the risk score or ranking for the patient is modified based on their calculated comorbidity burden. In a sixth step, all individual risk scores or rankings are analyzed to determine if there are any replacement drugs, vaccines, medications, dietary supplements, or medical devices within each respective category that might be used to replace any drugs, vaccines, medications, dietary supplements, or medical devices that have high risk scores and which the patient is currently using. The risk score or ranking for the combined drugs, vaccines, medications, dietary supplements, or medical devices categories from which the overall risk or score for the patient are then recalculated in order to assess potential changes or substitutions to the drugs, vaccines, medications, dietary supplements, or medical devices that the patient uses.

[0107] According to an exemplary embodiment, a method of evaluating safety risk associated with a drug, vaccine, medication, dietary supplement, and/or medical device includes receiving in a computerized system data regarding chemical analysis-related information regarding adverse event(s) and patient outcome(s) regarding the use of a drug, vaccine, medication, dietary supplement, and/or medical device. In some embodiments, the method also includes mapping or combining such chemical analysis-related data with case report or other data from an adverse event database, such as FAERS and similar global counterparts, to determine cost and safety parameters using the received data. Parameters are based on predetermined chemical analysis components and safety-related estimates of the predictive value of received data with regard to a possible downstream costs and safety risk or adverse event(s) and poor outcome(s) associated with the drug, vaccine, medication, dietary supplement, and/or medical device asset. The method also includes determining a risk score, ranking or the like regarding the safety risk(s) as a function of the chemical analysis and safety parameters.

[0108] According to another exemplary embodiment, a method of evaluating safety risk associated with a drug, vaccine, medication, dietary supplement, and/or medical device includes receiving in a computerized system data regarding safety-related information on the drug, vaccine, medication, dietary supplement, and/or medical device. In some embodiments, the method also includes determining one or more safety parameters using the received data.

Parameters are based on a predetermined safety-related estimate of the predictive value of received data with regard to a possible safety risk or adverse event associated with the drug, vaccine, medication, dietary supplement, and/or medical device asset. The method also includes determining a risk score, ranking or the like regarding the safety risk(s) as a function of one of more of the parameters.

[0109] In some embodiments, the system includes a processor linked to the computer memory, operable to execute programmed instructions, wherein the programmed instructions are configured to determine a safety-related parameter using received safety-related data from one, or multiple, sources. The parameter is based on a predetermined estimate of the safety-related risk value of received data with regard to possible safety risk(s), adverse event(s), side effect(s), or consequence(s) associated with the drug, vaccine, medication, dietary supplement, and/or medical device. The programmed instructions are also configured to determine a risk score, ranking, or the like, regarding the safety risk(s), adverse event(s), side effect(s), or consequence (s) as a function of the parameter.

[0110] According to another exemplary embodiment, a method of evaluating safety risk(s), adverse event(s), outcome(s), side effect(s), or consequence(s) associated with drug, vaccine, medication, dietary supplement, and/or medical device includes determining a safety-related score, ranking, or the like, parameter using information from one, or multiple, safety -related databases. The parameter is based on one or more safety-related risk estimates with regard to a possible downstream safety risk(s), adverse event(s), side effect(s), or consequence (s) associated with the drug, vaccine, medication, dietary supplement, and/or medical device. The method also optionally includes determining a comorbidity parameter value, and using such a comorbidity value to modify the risk score, ranking, or the like. The method can also include various other pre- or post-marketing parameter values, including safety or efficacy data from clinical trials, safety or efficacy data from claims databases, and the like, and using such to modify the risk score, ranking, or the like.

[0111] The plurality of predetermined parameters are generated by sampling safety-related information data from a plurality of cost, safety, adverse event, side effect, or consequence related databases, and by assigning risk points, scores, ranks, or the like for each of the plurality of cost, safety, adverse event, side effect, or consequence related information data with regard to potential safety-risk(s) in order to estimate a safety score, ranking, or the like, with regard to the drug, vaccine, medication, dietary supplement, and/or medical device. The method also includes determining a probability of the safety-risk, side effect, consequence, or adverse event as a function of the parameter.

[0112] In some embodiments combining the data obtained from a system for estimating the safety-related severity or level of risk associated with a given medical intervention with the data from an analytical test on a sample can generate a predictive value of the safety -related severity or level of risk associated with a given medical intervention based upon the results of an analytical test on a sample. In some embodiments the results of the predictive test can be used to determine if a batch of a drug or therapeutic has reduced effectiveness, higher effectiveness or reduced safety. In some embodiments the data generated from a predictive value can inform decisions by clinicians, pharmacists, drug manufacturers, healthcare providers, or health insurance providers.

[0113] In some embodiments, a score disclosed herein can rely on any one or combination of objective, science-based, independently generated data. In some embodiments, a score disclosed herein can be generated by a medical intervention manufacturer or an entity associated with the medical intervention. In some embodiments, a score disclosed herein can be generated by a private party not associated with a medical intervention manufacturer or medical intervention owner.

[0114] In some embodiments, a medical intervention cost can be affect by a score disclosed herein. In some embodiment, a medical intervention having a higher risk based on a score can be provided at a lower cost as compared to a reference. In some embodiments, a medical intervention having a lower risk based on a score can be provided at a higher cost as compared to a reference. In some embodiments a medical intervention can be at least in part be recalled or removed from the marketplace based on a score disclosed herein. In some embodiments, satisfaction of a particular criterion, feature, positive test or negative test disclosed herein can result in a score indicating a significantly high risk. In some embodiments, satisfaction of a single particular criterion, feature, positive test or negative test disclosed herein can result in a score indicating a significantly high risk irrespective of other low risk factors of the medical intervention. In some embodiments, a presence of one high risk factor of a medical intervention can over come all other positive low risk factor of a medical intervention and result in a high risk score. In some embodiments, a presence of one low risk factor of a medical intervention can overcome all other negative high risk factor of a medical intervention and result in a low risk score.

[0115] Disclosed herein are methods and systems for developing a risk score for a medical intervention.

Examples

Example 1.

[0116] As depicted in figure 1, real-time updated quality scores and optional alerts for a drug and manufacturer can be provided based on the methods and systems disclosed herein. Data related to healthcare data, for example FDA reports are inputted into a system in combination with chemical analysis data for a drug of interest. For example, Valsartan can be assessed based on healthcare data and the chemical analysis of samples from varying manufacturers to present a quality score. In some cases, a manufacturer can be identified as providing low quality product and an alert can be provided to a subject. In the example presented, DMF was identified in a manufacturer’ s product.

Example 2.

[0117] A quality score will have a maximum score (for example 100) and a lower limit (for example 0). The maximum score will be the most desirable and highest achievable score and the lower limit being the lowest and least desirable score. The default score given to any medical intervention can be the maximum score. Negative information associated with a particular medical intervention manufactured by a particular manufacturer will negatively impact a quality score of the medical intervention manufactured by the particular manufacturer. Positive information associated with a particular medical intervention manufactured by a particular manufacturer will positively impact a quality score of the medical intervention manufactured by the particular manufacturer. A score will be impacted by at least factors disclosed in Table 1 and can be weighted according to Table 2. Example 3.

[0118] A quality score will have a maximum score (for example 100) and a lower limit score (for example 0). The lower limit score will be the most desirable score and the maximum score being the least desirable score. The default score given to any medical intervention can be the lower limit score. Negative information associated with a particular medical intervention manufactured by a particular manufacturer will increase a quality score of the medical intervention manufactured by the particular manufacturer. Positive information associated with a particular medical intervention manufactured by a particular manufacturer will positively impact a quality score of the medical intervention manufactured by the particular manufacturer. A score will be impacted by at least factors disclosed in Table 1 and can be weighted according to Table 2

Example 4.

[0119] A quality score will have a maximum score (for example 100) and a lower limit score (for example 0). The lower limit score will be the most desirable score and the maximum score being the least desirable score. The default score given to any medical intervention can be between the maximum score and the lower limit score. Negative information associated with a particular medical intervention manufactured by a particular manufacturer will increase a quality score of the medical intervention manufactured by the particular manufacturer. Positive information associated with a particular medical intervention manufactured by a particular manufacturer will positively impact a quality score of the medical intervention manufactured by the particular manufacturer. A score will be impacted by at least factors disclosed in Table 1 and can be weighted according to Table 2.

Example 5.

[0120] A quality score will have a maximum score (for example 100) and a lower limit (for example 0). The maximum score will be the most desirable and highest achievable score and the lower limit being the lowest and least desirable score. The default score given to any medical intervention can be between the maximum score and the lower limit score. Negative information associated with a particular medical intervention manufactured by a particular manufacturer will negatively impact a quality score of the medical intervention manufactured by the particular manufacturer. Positive information associated with a particular medical intervention

manufactured by a particular manufacturer will positively impact a quality score of the medical intervention manufactured by the particular manufacturer. A score will be impacted by at least factors disclosed in Table 1 and can be weighted according to Table 2. [0121] While the disclosure has been described with reference to the aforementioned

specification, the descriptions and illustrations of the embodiments herein are not meant to be construed in a limiting sense. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the disclosure. Furthermore, it shall be understood that all aspects of the disclosure are not limited to the specific depictions, configurations or relative proportions set forth herein which depend upon a variety of conditions and variables. It should be understood that various alternatives to the embodiments of the disclosure described herein may be employed in practicing the disclosed method and systems. It is therefore contemplated that the disclosure shall also cover any such alternatives,

modifications, variations or equivalents. It is intended that the following claims define the scope of the disclosure and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

CLAIMS WHAT IS CLAIMED IS:

1. A method for developing a risk score for a medical intervention, said method

comprising:

a. determining one or more characteristics of a sample of said medical intervention using an analytical technique and assigning a first value based on said one or more characteristics; and

b. generating a risk score for said medical intervention based at least on said first value.

2. The method of claim 1, wherein said medical intervention is a pharmacological

intervention.

3. The method of claim 1, wherein said risk score is based solely on said first value.

4. The method of claim 1, further comprising assessing an additional criterion of said

medical intervention.

5. The method of claim 4, wherein said additional criterion comprises safety related

information, or physical data.

6. The method of claim 5, wherein said additional criterion comprises said safety related information.

7. The method of claim 6, wherein said safety related information comprises adverse event data or patient outcome data.

8. The method of claim 7, wherein risk of said medical intervention is increased based on a reporting of an adverse event or negative patient outcome.

9. The method of any one of claims 6-8, wherein said safety related information is from one or more pharmacovigilance center.

10. The method of claim 9, wherein said pharmacovigilance center comprises US FDA

Adverse Event Reporting System (FAERS), Australia’s“Therapeutic Goods

Administration,” Canada’s“Vigilance Adverse Reaction Online Database,” Europe’s “Eudra Vigilance,” Japan’s“Pharmaceuticals and Medical Devices Agency,” United Kingdom’s“Yellow Card Scheme,” France’s“pharmacovigilance database (ANSM),” or the World Health Organization’s“VigiBase.”

11. The method of claim 5, wherein said additional criterion comprises said physical data.

12. The method of claim 11, wherein said physical data comprises abnormalities in:

hardness, weight, density, size, shape, buoyancy, texture, color, turbidity, opacity, light reflection, dryness, hygroscopicity, static charge, conductivity, resistivity, magneticity, or any combination thereof.

13. The method of any one of claims 1-12, wherein said one or more characteristics

comprises a presence or an absence of an impurity or a contaminant.

14. The method of claim 13, wherein said one or more characteristics comprises a quantity of said impurity or said contaminant.

15. The method of claim 13 or 14, wherein said impurity or said contaminant is a disease causing impurity or contaminant.

16. The method of any one of claims 13-15, wherein risk of said medical intervention is increased based on a presence of said impurity or said contaminant.

17. The method of any one of claims 13-15, wherein risk of said medical intervention is decreased based on an absence of said impurity or said contaminant.

18. The method of any one of claims 1-17, wherein said one or more characteristics

comprises a quantity of an active pharmaceutical ingredient.

19. The method of claim 18, wherein risk of said medical intervention is increased when said active pharmaceutical ingredient is above or below a manufacturer or a regulatory agency specification.

20. The method of claim 18, wherein risk of said medical intervention is decreased when said active pharmaceutical ingredient is within a manufacturer or a regulatory agency specification.

21. The method of any one of claims 1-20, wherein said one or more characteristics

comprises a measure of dissolution of a pharmaceutical ingredient.

22. The method of any one of claims 1-21, wherein said one or more characteristics

comprise a measure of: an active pharmaceutical ingredient, dissolution of a

pharmaceutical ingredient, an inactive ingredient, an impurity, contaminant, a carcinogen, heavy metal, microbial contamination, residual solvent, outgassing product, particulates, foreign object, volatile compound, cross contamination of a pharmaceutical ingredient or any combination thereof.

23. The method of any one of claims 1-22, wherein said risk score is provided to a subject.

24. The method of any one of claims 1-23, wherein said analytical technique is nuclear magnetic resonance spectroscopy, mass spectroscopy, high-performance liquid chromatography, Fourier transform infrared spectroscopy, or Raman spectroscopy.

25. A system for performing said method of any one of claims 1-24.

26. A method for developing a risk score for a medical intervention, said method

comprising:

a. assessing safety related information for said medical intervention and assigning a first value based on said safety related information;

b. determining one or more characteristics of a sample of said medical intervention and assigning a second value based on said one or more characteristics; and c. generating a risk score for said medical intervention based on said first value and said second value.

27. The method of claim 26, wherein said medical intervention is a pharmacological

intervention.

28. The method of claim 26 or 27, wherein said safety related information comprises adverse event data or patient outcome data.

29. The method of claim 28, wherein said first value is increased based on a reporting of an adverse event or negative patient outcome.

30. The method of any one of claims 26-29, wherein said safety related information is from one or more pharmacovigilance center.

31. The method of claim 30, wherein said pharmacovigilance center comprises US FDA Adverse Event Reporting System (FAERS), Australia’s“Therapeutic Goods

32. The method of any one of claims 26-31, wherein said one or more characteristics

comprises a presence or an absence of an impurity or a contaminant.

33. The method of claim 32, wherein said one or more characteristics comprises a quantity of said impurity or said contaminant.

34. The method of any one of claims 32 or 33, wherein said impurity or said contaminant is a disease causing impurity or contaminant.

35. The method of any one of claims 32-34, wherein said second value is increased based on a presence of said impurity or said contaminant.

36. The method of any one of claims 32-34, wherein said second value is decreased based on an absence of said impurity or said contaminant.

37. The method of any one of claims 26-36, wherein said one or more characteristics

comprises a quantity of an active pharmaceutical ingredient.

38. The method of claim 37, wherein said second value is increased when said active pharmaceutical ingredient is above or below a manufacturer or a regulatory agency specification.

39. The method of claim 37, wherein said second value is decreased when said active

pharmaceutical ingredient is within a manufacturer or a regulatory agency specification.

40. The method of any one of claims 26-39, wherein said one or more characteristics

comprises a measure of dissolution of a pharmaceutical ingredient.

41. The method of claim 40, wherein said second value is increased when said measure of dissolution is above or below a manufacturer or a regulatory agency specification.

42. The method of claim 40, wherein said second value is decreased when said measure of dissolution is within a manufacturer or a regulatory agency specification.

43. The method of any one of claims 26-42, wherein said determining is performed using an analytical test.

44. The method of claim 43, wherein said analytical test is performed using a nuclear

magnetic resonance spectroscopy, mass spectroscopy, high-performance liquid chromatography, Fourier transform infrared spectroscopy, or Raman spectroscopy.

45. The method of claim 44, wherein said analytical test is performed using said Raman spectroscopy.

46. The method of any one of claims 43-45, wherein said analytical test comprises a plurality of analytical tests.

47. The method of any one of claims 26-46, wherein said risk score is provided to a subject.

48. A system for performing said method of any one of claims 26-47.