Efficacy and safety concerns are important reasons why the FDA requires multiple reviews before approval of new drugs.

The regulatory approval of new drugs by the Food and Drug Administration (FDA) is a long and complex process and often requires multiple cycles of review, potentially delaying patients' access to new and effective therapeutics. We used qualitative methods to characterize the safety and efficacy reasons why applications for novel therapeutics approved by the FDA between 2001 and 2011 required multiple review cycles prior to approval. Among ninety-six applications approved between 2001 and 2011 that required multiple review cycles, safety concerns contributed to seventy-four (77.1 percent) and efficacy concerns to forty-three (44.8 percent). Our study suggests that multiple review cycles appear to play an important role in allowing the FDA to protect public health and in ensuring adequate understanding of clinical benefits and risks prior to approval.

[1]  D. Carpenter,et al.  The political economy of FDA drug review: processing, politics, and lessons for policy. , 2004, Health affairs.

[2]  Khaled Bouri,et al.  Scientific and regulatory reasons for delay and denial of FDA approval of initial applications for new drugs, 2000-2012. , 2014, JAMA.

[3]  J. DiMasi,et al.  Pharmaceutical Innovation in the 21st Century: New Drug Approvals in the First Decade, 2000–2009 , 2011, Clinical pharmacology and therapeutics.

[4]  Peter Lurie,et al.  Financial conflict of interest disclosure and voting patterns at Food and Drug Administration Drug Advisory Committee meetings. , 2006, JAMA.

[5]  Harlan M. Krumholz,et al.  Clinical trial evidence supporting FDA approval of novel therapeutic agents, 2005-2012. , 2014, JAMA.

[6]  H. Krumholz,et al.  What have we learnt from Vioxx? , 2007, BMJ : British Medical Journal.

[7]  Harlan M Krumholz,et al.  Guest authorship and ghostwriting in publications related to rofecoxib: a case study of industry documents from rofecoxib litigation. , 2008, JAMA.

[8]  M. Chren,et al.  Narrative Review: The Promotion of Gabapentin: An Analysis of Internal Industry Documents , 2006, Annals of Internal Medicine.

[9]  Harlan M. Krumholz,et al.  Regulatory review of novel therapeutics--comparison of three regulatory agencies. , 2012, The New England journal of medicine.

[10]  H. Krumholz,et al.  The ADVANTAGE Seeding Trial: A Review of Internal Documents , 2008, Annals of Internal Medicine.

[11]  P. Ling,et al.  Every document and picture tells a story: using internal corporate document reviews, semiotics, and content analysis to assess tobacco advertising , 2006, Tobacco Control.

[12]  G. Connolly,et al.  How cigarette design can affect youth initiation into smoking: Camel cigarettes 1983-93 , 2002, Tobacco control.

[13]  J. Ross,et al.  Study of neurontin: titrate to effect, profile of safety (STEPS) trial: a narrative account of a gabapentin seeding trial. , 2011, Archives of internal medicine.