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To the Editor: In their Perspective article in priate, monitors adherence to a revised timetable.
this issue of the Journal, Woloshin et al.1 raise The reported status of a postmarketing require-
concerns about the status of postmarketing ment or commitment is based on the original
studies after new statutory authority was pro- timetable2; therefore, even when there is a well-
vided to the Food and Drug Administration justified change in the timetable, the status is
(FDA) in the FDA Amendments Act of 2007 reported as delayed until the next milestone is
(FDAAA). Although the authors intended to exam- met. The studies that Woloshin et al. categorized
ine the effect of the FDAAA on the completion as not started may actually have been initiated
of postmarketing requirements, their analysis of but not completed. Over time, advances in science,
postapproval studies from 2009 and 2010 com- changes in standards of care, and new clinical
bined FDAAA postmarketing requirements, other information can affect study feasibility, design
postmarketing requirements, and postmarketing requirements, and even the need for or the ap-
commitments. Under the FDAAA, the FDA has propriateness of a study. A manufacturer may
the authority to issue a requirement for a drug therefore terminate a study, or the FDA may re-
manufacturer to perform a postapproval study lease the postmarketing requirement or commit-
(i.e., a postmarketing requirement) to assess ment or replace it with a new one that is aligned
known or potential serious risks of a drug. with current science and practice.
Other postmarketing requirements are provided The FDA tracks these circumstances carefully
under different statutory authority. The FDA may and works with manufacturers to ensure that the
also enter into an agreement with a manufac- postmarketing requirement or commitment study
turer, wherein the manufacturer commits to provides the information needed for public health.
performing a postapproval study (i.e., a post- The agency can take enforcement actions if a
marketing commitment). An accurate analysis of postmarketing requirement (but not a postmar-
the effect of the FDAAA would evaluate the keting commitment) is not met. The type of
timeliness of FDAAA postmarketing require- enforcement action taken varies according to the
ments separately from that of other postmarket- type of authority under which the postmarketing
ing requirements and commitments. requirement was issued. Depending on the vio-
It is also important to understand how the lation, the FDA may give a manufacturer the
status of postmarketing requirements or com- opportunity when doing so is consistent with
mitments is determined. The FDA assesses the public health responsibility to voluntarily
progress of postmarketing requirements or com-
mitments using the original timetable that is this weeks letters
based on the nature of the study and specific
regulatory categories. Many factors influence 1201 FDA Oversight of Postmarketing Studies
the timely conduct of a study; for example, low 1202 Single-Nephron Glomerular Filtration Rate
use of a product on the market or changes in the
in Healthy Adults
standard of care can reduce the number of pa-
tient records available for pharmacoepidemio- 1204 Glucocorticoid Sparing of Benralizumab
logic studies. The FDA assesses the justification in Asthma
for any delays and, if the justification is appro-
take prompt, corrective action before the agency Disclosure forms provided by the authors are available with
the full text of this letter at NEJM.org.
initiates an enforcement action.3
The FDA is dedicated to improving the over- This letter was updated on September 22, 2017, at NEJM.org.
sight of postmarketing requirements and com-
mitments, updating the public regularly, and 1. Woloshin S, Schwartz LM, White B, Moore TJ. The fate of
FDA postapproval studies. N Engl J Med 2017;377:1114-7.
improving the clarity of our reporting. We think 2. Guidance for industry:reports on the status of postmarket-
that it is reassuring that as of fiscal year 2015, a ing study commitments implementation of section 130 of the
total of 88% of postmarketing requirements over- Food and Drug Administration Act of 1997. Rockville, MD:Food
and Drug Administration, February 2006 (https://w ww.fda.gov/
all and 89% of FDAAA postmarketing require- downloads/Drugs/GuidanceComplianceRegulatoryInformation/
ments were progressing according to their origi- Guidances/UCM080569.pdf).
nal schedules.4 3. Food and Drug Administration. Inspections, compliance,
enforcement, and criminal investigations (https://w ww.fda.gov/
Mwango Kashoki, M.D., M.P.H. ICECI/EnforcementActions/WarningLetters/ucm278624.htm).
Cathryn Lee, M.S.N. 4. Food and Drug Administration. Report on the performance
of drug and biologics firms in conducting postmarketing require-
Peter Stein, M.D.
ments and commitments; availability. Fed Regist 2016;81(228):
Food and Drug Administration 85573-9 (https://www.federalregister.gov/d/2016-28442).
Silver Spring, MD
mwango.kashoki@fda.hhs.gov DOI: 10.1056/NEJMc1709185