Commentary: The risk of over-regulationBMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d3021 (Published 14 May 2011) Cite this as: BMJ 2011;342:d3021
All rapid responses
We commend the BMJ on a strong series of articles on "the trouble
with medical devices." However, we think there are serious flaws in the
arguments advanced by DiMario et al that the device approval process
should be less stringent and that doctors should solely determine which
devices have the optimal safety and effectiveness to use in their
patients. (1) Unfortunately, physicians do not have access to all of the
relevant data for high-risk devices as it either was not obtained or is
missing or considered proprietary and, thus, not available. For example,
we have found that for the highest-risk cardiovascular devices approved by
the FDA, 14% of studies did not list a primary endpoint and 88% of
available primary endpoints were surrogates, which may have questionable
relevance to actual patient outcomes. (2) There was also a significant
amount of missing data, as seventy-eight percent of primary endpoints had
a discrepancy between the number of patients enrolled in the study and the
number analyzed for the primary endpoint. Even when these data are
available, it would be difficult to determine to whom they should be
applicable; this is because the mean age for clinical trial populations
was stated for only 71% of studies and enrollment by sex in 72%. Although
there are many instances of important differences in device safety and
efficacy by sex, only 41% of studies even looked for these differences.
Regrettably, there is even less available data in the U.K. The
investigation by Heneghan et al. into field safety notices showed a
dangerous lack of data for recalled devices - despite significant efforts
including contacting manufacturers, the authors were unable to ascertain
the amount of premarket clinical testing and even what type of problems
led to most recalls. (4) These data are woefully inadequate to enable
doctors "to choose only well proved devices for their patients." (1) It is
essential to have more transparency and full access to the data reviewed
by both the FDA and EU-accredited notifying bodies. (5-7)
Further, device approval, particularly for high-risk devices, would
benefit from a process which requires high-quality data with clinical
outcomes as well as vigorous post-marketing surveillance because devices
are implanted permanently and long-term follow-up is essential. The
authors cite the MitraClip as an example of a device which could reach
full potential since it received a CE mark and has been used in Europe
since 2008 but does not have Food and Drug Administration (FDA) approval.
However, the hazards of this approach are illustrated as the device's
manufacturer initiated a recall of the MitraClip on May 9, due to serious
adverse events and one patient has possibly died due to complications from
the device. (8) Billingsley and Cohen note six additional devices approved
in Europe but rejected by the FDA. (9) While we would favor strengthening
the quality of the evidence in the FDA premarket approval process (2, 3,
10), there is perhaps even more room for improvement in the European
regulatory system. It is the responsibility of regulatory bodies to
protect the public health by ensuring the safety and efficacy of devices.
Only randomized controlled trials with blinding when possible and adequate
follow-up of meaningful clinical endpoints that demonstrate safety and
efficacy can ensure that high-risk devices will lead to beneficial patient
(1) Di Mario C, James S, Dudek D, Sabate M, Degertekin M.
Commentary: The risk of over-regulation. BMJ. 2011;342:d3021.
(2) Dhruva SS, Bero LA, Redberg RF. Strength of Study Evidence
Examined by the FDA in Premarket Approval of Cardiovascular Devices. JAMA.
(3) Dhruva SS, Bero LA, Redberg RF. Gender Bias in Studies for Food
and Drug Administration Premarket Approval of Cardiovascular Devices. Circ
Cardiovasc Qual Outcomes 2011;4:165-171.
(4) Heneghan C, Thompson M, Billingsley M, Cohen D. Medical-device
recalls in the UK an the device-regulation process: retrospective review
of safety notices and alerts. BMJ Open 2011;doi: 10.1136.
(5) Redberg RF. Medical Devices and the FDA Approval Process:
Balancing Safety and Innovation. Comment on "Prevalence of Fracture and
Fragment Embolization of Bard Retrievable Vena Cava Filters and Clinical
Implications Including Cardiac Perforation and Tamponade." Arch Int Med.
(6) Thompson M, Heneghan C, Billingsley M, Cohen D. Medical device
recalls and transparency in the UK. BMJ. 2011;342:d2973.
(7) O'Connor AB. The need for improved access to FDA reviews. JAMA.
(8) Hughes S. MitraClip recalled. Heartwire Clinical Cardiology Web
site. http://www.theheart.org/article/1223259.do. Accessed May 20, 2011.
(9) Cohen D, Billingsley M. Europeans are left to their own devices.
(10) Chen CE, Dhruva SS, Bero LA, Redberg RF. Inclusion of Training
Patients in US Food and Drug Administration Premarket Approval
Cardiovascular Device Studies. Arch Intern Med. 2011;171:534-539.
Competing interests: Dr. Redberg is a member of the FDA Circulatory System Devices Panel
Prof. Dariusz Dudek has received research grants or served as
consultant/ advisory board member for Abbott, Adamed, AstraZeneca,
Biotronik, Balton, Bayer, BBraun, BioMatrix, Boston Scientific, Boehringer
Ing., Bristol-Myers Squibb, Cordis, Cook, Eli Lilly, EuroCor, Glaxo,
Invatec, Medtronic, Medicines Company, MSD, Nycomed, Orbus-Neich, Pfizer,
Possis, Promed, Sanofi-Aventis, Siemens, Solvay, Terumo, Tyco.
Competing interests: Prof. Dariusz Dudek has received research grants or served as consultant/ advisory board member for Abbott, Adamed, AstraZeneca, Biotronik, Balton, Bayer, BBraun, BioMatrix, Boston Scientific, Boehringer Ing., Bristol-Myers Squibb, Cordis, Cook, Eli Lilly, EuroCor, Glaxo, Invatec, Medtronic, Medicines Company, MSD, Nycomed, Orbus-Neich, Pfizer, Possis, Promed, Sanofi-Aventis, Siemens, Solvay, Terumo, Tyco.