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