MCPHS University International Center for Pharmaceutical Economics and Policy

1. MCPHS University International Center for Pharmaceutical Economics and Policy 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 American Public Health Association, Boston, Nov. 5, 2013

2. Presenter Disclosures Lita Araujo (1)The following personal financial relationships with commercial interests relevant to this presentation existed during the past 12 months: “No relationships to disclose”

3. MCPHS University International Center for Pharmaceutical Economics and Policy Lita Araujo, MS Soeun Kwon, MS Michael Montagne, PhD Enrique Seoane, PhD American Public Health Association, Boston, Nov. 5, 2013

4. Outline • Background • Objectives • Data Sources and Methods • Results • Conclusions • Policy Recommendations

5. 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

6. 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

7. Data Sources • Dailymed - National Institute of Health • Drugs@FDA - FDA • Physician's Desk Reference 1980-2013

8. 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-squaretestto assess differences in proportions

9. Defining Hypothesized MOAs Equivocating Phrases Remains to be fully established Appears to be Not determined May be involved Equivocating Words Likely Probably Postulate Suggest

10. Outline • Background • Objectives • Data Sources and Methods • Results • Conclusions • Policy Recommendations

11. Sample 902 new drugs and biologics approved by the FDA during 1980-2012 32 products were excluded 870 products included in the study

12. MOA Status Hypothesized 252 (29%) Known 579 (67%) Unknown 39(4%)

13. MOA Status by Decade

14. 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

15. MOA Status by Anatomical Group ATC-1

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

17. MOA Status by Therapeutic Subgroup ATC-2Dermatologicals

18. MOA Status by Therapeutic Subgroup ATC-2Nervous System

19. 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

20. 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

21. MCPHS University International Center for Pharmaceutical Economics and Policy 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 Lita Araujo, MS; Soeun Kwon, MS; Michael Montagne, PhD; Enrique Seoane, PhD American Public Health Association, Boston, Nov. 5, 2013