What do we know about the mechanism of action of drugs in the different drug classes? Assessment of the pharmaceuticals approved by the FDA between 1980 and 2012

BACKGROUND: Mechanism of action (MOA) describes a biochemical event indicative of a drug's pharmacological activity. The U.S. Food and Drug Administration (FDA) requires MOA to be described on the drug's label. The MOA is important because it assists health providers in understanding the therapeutic applications and possible adverse reactions of a drug. OBJECTIVE: Assessment of the MOA for the Anatomical Therapeutic Chemical (ATC) classes of new drugs and biologics approved by the FDA between 1980 and 2012. METHODS: Information was collected from drug labels available online at the National Institute of Health, and the FDA, and in hard copy of the Physician's Desk Reference versions 1980-2012. Data were collected by 2 researchers and the MOAs classified as: known, unknown, or hypothesized. Another investigator resolved observed differences. The analysis was done at the levels of the anatomical main group (ATC-1) and the therapeutic main group (ATC-2). Chi-square was used to assess differences in proportions. RESULTS: 902 new drugs and biologics (811 and 91 respectively) belonging to 14 ATC-1 classes were approved by the FDA during the study period. The MOA was known for 67.6% of new drugs and 85.2% of biologics. Blood and blood forming organs (95.3%), systemic hormonal preparations, excluding sex hormones and insulins (94.1%), and antiinfectives for systemic use (92.9%) were the ATC classes with the highest percentage of known MOA. Nervous system (19.8%), dermatologicals (31.4%), and musculo-skeletal system (45.0%) were the ATC classes with the lowest proportion of known MOA. The analysis of the 33 ATC-2 classes indicated that the highest proportion of known MOAs were in the contrast media (100%), other alimentary tract and metabolism products (100%), muscle relaxants (100%), and diagnostic agents (100%). The lowest percentages of known MOAs were in the antiinflammatory and antirheumatic products (0%), psychoanaleptics (3.8%), and antiepileptics (6.3%). No significant differences by therapeutic class were observed in terms of known MOA between orphan/non-orphan drugs, marketed/discontinued products, and safety withdrawals. CONCLUSIONS: An important number of therapeutic classes had 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. FDA should consider standardizing the label with regard to MOA and encourage manufacturers to continue collecting evidence post-marketing to confirm a drug's MOA.