New research published by the Manhattan Institute for Policy Research (MIPR), a right-leaning think tank which focuses in part on pharmaceutical regulation policy, indicates that there are wide gaps in performance among the US Food and Drug Administration's (FDA) review divisions, resulting in a "productivity gap" that has left some patients without ready access to new therapies.
MIPR's research report, An FDA Report Card: Wide Performance Found Among Agency's Drug Review Divisions, is intended to provide an "objective examination" of the speed of FDA's reviews. FDA has long come under intense criticism from outside groups, which either criticize it for approving products too quickly or too slowly.
The problem with those arguments, MIPR's research model shows, is that both sides can be right simultaneously. For example, one of FDA's review divisions might be exceedingly quick to review and approve some products, while another might be extraordinarily slow to review and reluctant to approve other products.
With this in mind, the study's authors-Joe DiMasi and Christopher-Paul Milne of the Tufts Center for the Study of Drug Development and Alex Tabarrok, a prominent economist affiliated with George Mason University-looked at nearly 200 pharmaceutical and biological products brought to market between 2004 and 2012.
'Wide Variation in Division Performance'
What they found, they said, was a "wide variation in division performance." Some review divisions, such as the Center for Drug Evaluation and Research's (CDER) oncology and antiviral divisions, approved drugs with nearly twice the speed as the next-fastest divisions, and nearly four times as quickly as CDER's slowest division.
|CDER Review Division||Mean Time to Approval (Days)||Average # of Review Cycles||% Products With Priority Rating||% Products With Fast-Track or Accelerated Approval|
|Metabolism and Endocrinology||442||1.32||15.8%||0.0%|
|Reproductive and Urologic||488||1.40||0.0%||0.0%|
|Pulmonary, Allergy, and Rheumatology||538||1.83||41.7%||25.0%|
|Anesthesia, Analgesia, and Addiction||582||1.50||42.9%||0.0%|
|Cardiovascular and Renal||769||1.60||40.0%||6.7%|
Median approval times bore similarly large variations, the research showed, but the report did not list the exact data (though it is in bar chart form on page eight of the report).
Review efficiency was another aspect of FDA the report focused on. In particular, how good are FDA's review divisions at meeting their review targets (known as PDUFA dates after the Prescription Drug User Fee Act), and how many staff does it take to generate a single approval?
|CDER Review Division||Average # of INDs Received as % of Staff||Average # of NDAs Received as % of Staff||PDUFA Goals Met|
|Anesthesia, Analgesia, and Addiction||0.965||0.167||85.7%|
|Cardiovascular and Renal||0.634||0.165||80.0%|
|Metabolism and Endocrinology||1.037||0.182||84.2%|
|Pulmonary, Allergy, and Rheumatology||0.700||0.138||91.7%|
|Reproductive and Urologic||0.630||0.181||100%|
The report's authors said they found little correlation between productivity and workload, or even between a drug's fast-track, priority review or accelerated approval status.
Other factors were considered by the researchers, as well. For example, were the drugs subject to a clinical hold? Were they given a block box warning? Were they given post-marketing requirements that sped up their approval? Did FDA ask for an advisory panel's advice? And how long was the drug in clinical development?
|CDER Review Division||% of Drugs Subject to AdComm||% of Drugs Subject to Clinical Hold||% of Drugs Given Black Box Warning||Average # of PMRs Per Approved Drug||Length (in Months) of Clinical Development|
|Anesthesia, Analgesia, and Addiction||42.9%||16.1%||35.7%||2.00||63.7|
|Cardiovascular and Renal||40.0%||3.8%||53.3%||1.57||79.1|
|Metabolism and Endocrinology||47.4%||16.5%||21.1%||4.38||94.0|
|Pulmonary, Allergy, and Rheumatology||66.7%||15.6%||16.7%||2.50||75.6|
|Reproductive and Urologic||41.3%||6.7%||10.0%||2.14||77.8|
For the researchers, the data showed that FDA performance defies easy explanation across divisions.
"An examination of numerous variables suggests that the performance of the leading divisions cannot be explained by a lower workload, differences in the type and complexity of the drugs under review, or a diminution in safety," the reviewers wrote. "Indeed, Oncology and Anti-Viral had a relatively higher workload than other units while the divisions that appeared to be below-average performers (Cardiovascular/Renal, Neurology, and Psychiatry) had a lower workload."
Further research will be needed to identify "best practices" in FDA's highest-performing divisions and apply them throughout FDA, the paper explained. In addition, the authors suggested that FDA establish an internal "cadre of shock troops" to alleviate regulatory resource demands. Given current demands on FDA resources, other outside entities such as the National Institutes of Health or C-Path officials might be useful in this regard.
Manhattan Institute Report