Transcript No relationships to disclose

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
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”
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
Outline
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Background
Objectives
Data Sources and Methods
Results
Conclusions
Policy Recommendations
Background
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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
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Methods
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MOA classification
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WHO classification system
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Known, hypothesized, or unknown
Three researchers classified the MOA
Anatomical main group (ATC-1)
Therapeutic sub group (ATC-2)
Chi-square test to assess differences
in proportions
Defining Hypothesized MOAs
Equivocating Phrases
Equivocating Words
Remains to be fully
established
Likely
Appears to be
Not determined
May be involved
Probably
Postulate
Suggest
Outline
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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 excluded
870 products included in the study
MOA Status
Known
579 (67%)
Hypothesized
252 (29%)
Unknown
39(4%)
MOA Status by Decade
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
4%
41%
5%
4%
26%
24%
69%
72%
1990-99
2000-12
55%
1980-89
Known
Hypothesized
Unknown
Chi-square test
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Orphan drugs vs. Non-orphan drugs
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p-value 0.3877
Marketed vs. Discontinued drugs
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P-value 0.0320
By decade: 80’ p-value 0.0049
90’ p-value 0.0755
MOA Status by Anatomical Group ATC-1
Nervous System 12%
72%
16%
Dermatologicals
36%
45%
19%
Musculo-Skeletal Syst.
42%
50%
8%
Sensory Organs
57%
43%
0%
Antiparasitic Products
59%
41%
0%
Cardiovascular System
68%
30%
2%
Respiratory System
69%
31%
0%
2%
Antineoplastic
69%
29%
Genito Urinary System
81%
15% 4%
Alimentary Tract
81%
14% 5%
Systemic Hormonal Prep.
88%
12% 0%
Blood Forming Organs
91%
9% 0%
Antiinfectives Syst. Use
92%
7% 1%
Diagnostic
92%
7% 1%
Known
0%
50%
Hypothesized
Unknown
100%
MOA Status by Therapeutic Subgroup ATC-2
Musculo-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-2
Dermatologicals
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%
Therapeutic Subgroup
MOA Status by Therapeutic Subgroup ATC-2
Nervous 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
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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
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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 postmarketing to confirm a drug’s MOA
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