What Do We Know About the Mechanism of Action of Drugs in the

Different Drug Classes? Assessment of Pharmaceuticals Approved by the FDA

between 1980 and 2012

MCPHS UNIVERSITYINTERNATIONAL CENTER FOR

PHARMACEUTICAL ECONOMICS AND POLICY

American Public Health Association, Boston, Nov. 5, 2013

Presenter Disclosures

(1)The following personal financial relationships with commercial interests relevant to this presentation existed during the past 12 months:

Lita Araujo

“No relationships to disclose”

Lita Araujo, MSSoeun Kwon, MS

Michael Montagne, PhDEnrique Seoane, PhD

MCPHS UNIVERSITYINTERNATIONAL CENTER FOR

PHARMACEUTICAL ECONOMICS AND POLICY

American Public Health Association, Boston, Nov. 5, 2013

Outline

Background Objectives Data Sources and Methods Results Conclusions Policy Recommendations

Background

Mechanism of action (MOA) describes a biochemical event indicative of a drug’s pharmacological activity

FDA requires MOA on the drug’s label* MOA assists health providers to

understand therapeutic applications and possible adverse reactions

* FDA. Clinical Pharmacology Section of Labeling for Human Prescription Drug and Biological Products - Content and Format. Feb 2009

Objectives

Assessment of the MOA, as described in the product label, for the Anatomical Therapeutic Chemical (ATC) classes of new drugs and biologics approved by the FDA between 1980 and 2012

Data Sources

Dailymed - National Institute of Health Drugs@FDA - FDA Physician's Desk Reference 1980-2013

Methods MOA classification

· Known, hypothesized, or unknown· Three researchers classified the MOA

WHO classification system· Anatomical main group (ATC-1) · Therapeutic sub group (ATC-2)

Chi-square test to assess differences in proportions

Defining Hypothesized MOAs

Equivocating Phrases

Remains to be fully established

Appears to be

Not determined

May be involved

Equivocating Words

Likely

Probably

Postulate

Suggest

Outline

Background Objectives Data Sources and Methods Results Conclusions Policy Recommendations

Sample

902 new drugs and biologics approved by the FDA during 1980-2012

32 products were excluded870 products included in the study

MOA Status

Known 579 (67%)

Hypothesized252 (29%)

Unknown39(4%)

MOA Status by Decade

1980-89 1990-99 2000-120%10%20%30%40%50%60%70%80%90%

100%

55%69% 72%

41%26% 24%

4% 5% 4%

Known Hypothesized Unknown

Chi-square test

Orphan drugs vs. Non-orphan drugs· p-value 0.3877

Marketed vs. Discontinued drugs· P-value 0.0320· By decade: 80’ p-value 0.0049

90’ p-value 0.0755

MOA Status by Anatomical Group ATC-1

DiagnosticAntiinfectives Syst. UseBlood Forming Organs

Systemic Hormonal Prep.Alimentary Tract

Genito Urinary SystemAntineoplastic

Respiratory SystemCardiovascular SystemAntiparasitic Products

Sensory OrgansMusculo-Skeletal Syst.

DermatologicalsNervous System

0% 20% 40% 60% 80% 100%92%92%91%

88%81%81%

69%69%68%

59%57%

42%36%

12%

7%7%9%12%

14%15%

29%31%

30%41%43%

50%45%

72%

1%1%

0%5%4%2%0%2%0%0%8%

19%16%

Known Hypothesized Unknown

MOA Status by Therapeutic Subgroup ATC-2Musculo-Skeletal System

Therapeutic Subgroup n Known Hypothesized Unknown

Antigout Preparations 2 100.00% 0.00% 0.00%

Muscle Relaxants 12 91.67% 8.33% 0.00%

Drugs for Treatment of Bone Diseases 7 57.14% 42.86% 0.00%

Topical Products Joint /Muscular Pain 1 0.00% 100.00% 0.00%

Other Drugs Disorders Musc.-Skel. System 2 0.00% 100.00% 0.00%

Antiinflammatory and Antirheumatic Prods 16 0.00% 81.25% 18.75%

MOA Status by Therapeutic Subgroup ATC-2Dermatologicals

Therapeutic Subgroup n Known Hypothesized Unknown

Emollients and Protectives 1 100.00% 0.00% 0.00%

Preparations Treat. of Wounds and Ulcers 1 100.00% 0.00% 0.00%

Antipsoriatics 3 66.67% 0.00% 33.33%

Antibiotics and Chemotherapeutics 8 50.00% 12.50% 37.50%

Antifungals for Dermatological Use 8 37.50% 62.50% 0.00%

Corticosteroids, Dermatological Preps 5 0.00% 100.00% 0.00%

Anti-Acne Preparations 4 0.00% 75.00% 25.00%

Other Dermatological Preparations 1 0.00% 0.00% 100.00%

MOA Status by Therapeutic Subgroup ATC-2Nervous System

Therapeutic Subgroup n Known Hypothesized Unknown

Other Nervous System Drugs 10 40.00% 50.00% 10.00%

Analgesics 13 23.08% 76.92% 0.00%

Psycholeptics 25 12.00% 48.00% 40.00%

Anesthetics 10 10.00% 70.00% 20.00%

Anti-Parkinson Drugs 10 10.00% 90.00% 0.00%

Psychoanaleptics 26 3.85% 84.62% 11.54%

Antiepileptics 16 0.00% 87.50% 12.50%

Conclusions An important number of therapeutic classes

have a low proportion of known MOAs Many of the drugs belonging to those

classes are used by large number of patients The lack of information about MOA could

result in safety and efficacy problems

Policy Recommendations FDA could develop standardized template

for product label with regard to MOA FDA could require compliance with its

guidelines and template by manufacturers FDA could encourage manufacturers to

continue collecting evidence post-marketing to confirm a drug’s MOA

What Do We Know About the Mechanism of Action of Drugs in the

Different Drug Classes? Assessment of Pharmaceuticals Approved by the FDA

between 1980 and 2012Lita Araujo, MS; Soeun Kwon, MS;

Michael Montagne, PhD; Enrique Seoane, PhD

MCPHS UNIVERSITYINTERNATIONAL CENTER FOR

PHARMACEUTICAL ECONOMICS AND POLICY

American Public Health Association, Boston, Nov. 5, 2013