In an analysis of publicly available US Food and Drug Administration (FDA) documents from 448 efficacy trials of 188 novel therapeutics approved between 2005 and 2012, Downing and colleagues examined the strength of the clinical evidence supporting the approval decisions. The authors found wide variation in the quality of evidence used as a basis for approvals, particularly in the choice of comparators and end points and in trial duration, size, and completion rate.
Related Editorial, Related Articles 1 and 2
Author Video Interview
To identify reasons for US Food and Drug Administration (FDA) approval delay or denial of new molecular entities (NMEs; an active ingredient never before marketed in the United States), Sacks and colleagues reviewed 302 drug applications for NMEs submitted to the FDA between 2000 and 2012. The authors identified several potentially preventable deficiencies that led to delays in approval, including failure to select optimal drug doses and study end points that reflect a clinically meaningful effect. A common reason for approval denial was poor efficacy compared with standard of care. In an Editorial, Goodman and Redberg discuss FDA decision making regarding drugs and devices.
Continuing Medical Education
The US Food and Drug Administration (FDA) evaluation of high-risk medical devices through the premarket approval (PMA) pathway includes review of preclinical and clinical data relating to safety and effectiveness. Changes to approved devices are implemented through the PMA supplement process, which may not require additional clinical testing. In a review of the FDA database for all cardiac implantable electronic devices approved from 1979-2012 (77 original PMA; 5825 PMA supplements), Rome and colleagues found that many cardiac implantable devices currently in use were approved through the PMA supplement process and deemed safe and effective without requiring new clinical data.
MicroRNAs—small, noncoding single-stranded RNA sequences—play a role in oncogenesis. In a case-control study that involved 409 patients with pancreatic cancer, 25 patients with chronic pancreatitis, and 312 healthy blood donors, Schultz and colleagues assessed microRNA expression in whole blood samples. The authors identified 2 panels of microRNA that may distinguish patients with pancreatic cancer from healthy controls; however, further research is needed to assess whether these findings have clinical implications for early detection of pancreatic cancer. In an Editorial, Buchsbaum and Croce discuss microRNA expression in pancreatic cancer.
When applying clinical trial results to individual patients in clinical practice, physicians may consider results derived from a subgroup of the trial participants whose characteristics more closely resemble those of the patient being seen. However, such subgroup effects can prove to be spurious. In this article in the Users’ Guides to the Medical Literature series, Sun and colleagues provide guidance for assessing the validity of subgroup analyses and for deciding whether to use the results to guide patient care.
A 52-year-old woman reports a decline in exercise tolerance and exertional right buttock and thigh pain that resolves promptly with rest. Recent onset hypertension is well controlled with lisinopril. On examination, the patient has a high-pitched systolic bruit over the right subcostal region and umbilicus. A computed tomography angiogram reveals “beading” of the right renal artery and a stenosis in the right external iliac artery. What would you do next?
Highlights. JAMA. 2014;311(4):327-329. doi:10.1001/jama.2013.279290