What have we learnt from Vioxx?
BMJ 2007; 334 doi: https://doi.org/10.1136/bmj.39024.487720.68 (Published 18 January 2007) Cite this as: BMJ 2007;334:120
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What did we learn?
That a drug can be marketed to physicians in such a way that they will
prescribe
this for patients at 10 times the cost of over the counter anti-
inflammatories
when it was never demonstrated to be better or safer in terms of real
clinical
outcomes. I suppose that we can blame Merck and the FDA for promoting and
approving the use of Vioxx but they were not responsible for choosing to
prescribe Vioxx over many cheaper products. Who wrote the
prescriptions...and
why? That's what we should seek to learn: the factors that result in
irrational
prescribing.
Competing interests:
None declared
Competing interests: No competing interests
23 February 2007
Fiona Godlee
Editor-in-Chief
British Medical Journal
Dear Fiona Godlee:
The authors of “What have we learnt from Vioxx?” featured in BMJ
2007; 334:120-123 (20 January) refer to their “recent involvement in
litigation at the request of plaintiffs” and the “unique opportunity” it
presented them to examine and reflect upon court documents, research and
other evidence relating to Vioxx. And, suggesting the story to be told
was complete and balanced – perhaps even objective – the authors offer to
share “important lessons.”
But the story they offered sounded surprisingly like an opening
statement by plaintiff attorney Mark Lanier, whose picture graced the
pages of the BMJ article. Coincidently, the article was published just as
Mr. Lanier started his current Vioxx case against Merck & Co., Inc.,
of Whitehouse Station, N.J., USA – another case in which Dr. Harlan
Krumholz was paid to testify for the plaintiff.
To be clear about who’s who, I am an attorney representing Merck
& Co., Inc. in the Vioxx litigation. As the authors disclosed in the
article, all four of the authors have been consultants to plaintiffs’
attorneys in the Vioxx litigation. Dr. Krumholz testified earlier this
month for Mr. Lanier in the pending New Jersey Vioxx cases and
acknowledged that he and his assistants will be paid roughly $300,000 for
the work they have done to date for Vioxx plaintiffs. One of his co-
authors, Dr. David Egilman, previously testified as an expert witness
against Merck & Co., Inc. in the Vioxx litigation, also for Mark
Lanier. Dr. Egilman also served as an expert consultant for plaintiffs in
the Zyprexa litigation against Eli Lilly, again in consultation with the
Lanier Law Firm, which was founded by Mark Lanier.
Despite what the authors claimed was a thorough examination and
reflection upon the “accumulated court documents, research and other
evidence,” Dr. Krumholz got several important facts wrong and omitted many
others from his purported lesson. While this list is not exhaustive, the
following warrants correction:
The Merck & Co., Inc.-sponsored study that measured metabolites
of prostacyclin in the urine was published and widely discussed before
Vioxx was ever approved for marketing. Merck & Co., Inc. included the
study in the regulatory filings that led to the FDA approval of Vioxx.
Further, Merck & Co., Inc. discussed the study and other relevant data
with distinguished outside scientific consultants, who also considered
data suggesting that medicines in this class might be cardio-protective.
In response to the recommendations of its outside advisors, Merck
& Co., Inc. instituted a cardiovascular standard operating procedure
that established a panel of independent experts to adjudicate in a blinded
fashion all investigator-reported cardiovascular events from future Merck
& Co., Inc. clinical trials. Merck & Co., Inc. took this action
to rigorously monitor the cardiovascular safety profile of the medicine
and Merck & Co., Inc. continued to study the medicine in large-scale
trials after it was on the market. And incidentally, an increasing body
of evidence casts doubt on the decade-old hypothesis that Cox-2 might be
the mediator of prostacyclin in the vascular endothelium.
Merck & Co., Inc.'s new drug application for Vioxx included
approximately 60 randomized clinical trials in approximately 10,000
patients. These trials, which in the main compared Vioxx either to the
traditional non-steroidal anti-inflammatory drugs (ibuprofen and
diclofenac), or to placebo, yielded no evidence of statistically
significant thrombotic cardiovascular events associated with Vioxx.
With regard to Merck & Co., Inc.’s VIGOR study, the authors
appear to falsely imply that the cardiovascular events in VIGOR were not
subject to the adjudication procedure. They were. Indeed, Merck &
Co., Inc. convened a data safety monitoring board composed of highly-
qualified outside rheumatologists and gastroenterologists and a
biostatistician -- a fitting line-up for a gastrointestinal outcomes study
in a rheumatoid arthritis population. The implication of conflict of
interest with which the authors seek to taint that Board’s distinguished
chair comes with particularly ill grace from physicians using a medical
journal as a platform for the very opinions a plaintiff’s lawyer pays them
to give.
In trumpeting the “expression of concern” published by The New
England Journal of Medicine in 2006, with regard to the use of a cutoff
date for data in the VIGOR publication, the authors fail to point out that
Merck & Co., Inc. presented the post-cutoff data publicly at the U.S.
Food and Drug Administration Advisory Committee hearings in February 2001.
Despite their participation in the Vioxx litigation and the alleged
thorough review of court documents, the authors also failed to mention
that the editor of NEJM admitted in sworn testimony that he knew of the
post-cutoff data from its publication in August 2001, in the very JAMA
article the authors cite. And the fact that the NEJM’s editors
“expression of concern” was published five years later and after trial
lawyers sought their deposition was somehow not relevant to the lessons
the authors offered.
The medical and scientific communities continue to study and build
upon the collective knowledge about Cox-2 and the medicines that affect
it. As for the important questions of who knew what and when with regard
to Vioxx, the authors of the BMJ article present only a fraction of the
facts necessary to answer those questions and, as you would expect given
the authors’ support for the plaintiffs’ cause, the facts they chose to
include were all favorable to the plaintiffs’ theories.
I'm paid to represent Merck & Co., Inc. so I will not offer my
views and claim them to be objective. But I suggest your readers consider
that in a jury trial, Merck & Co., Inc. and the plaintiffs each have
an opportunity to present their respective positions and the supporting
evidence. If the Vioxx story were as Dr. Krumholz and his colleagues
suggest, one might wonder how it could be that to date Merck & Co.,
Inc. has won more than two-thirds of the cases decided by juries so far.
Ted Mayer
Hughes Hubbard & Reed LLP
New York, NY
Competing interests:
I am an attorney representing Merck & Co., Inc. in the Vioxx litigation.
Competing interests: No competing interests
I read with great interest the article by Krumholz H. et al. about
VIOXX case. As a methodologist, I would be tempted to precise that
assessment of benefits and risks in clinical trials is complex and not as
easy as it seems :
1. A clinical trial is often designed to assess benefit of a new drug. The
study is designed to show a difference for this primary outcome. Then
assessment of risk (secondary outcome) can be limited by an inadequate
sample size. Statistical power might be insufficient to show a difference
in terms of adverse events (AE) : results are not statistically
significant for AE even if risk exists.
2. Adverse events when they are unexpected are difficult to isolate in
clinical trials. In the case of VIOXX, AE was myocardial infarction (MI).
MI is a common event in the general population and was not expected : this
increased difficulty to conclude on elevation of risk of MI with
rofecoxib. Elevated delays between treatment and AE also made it difficult
to conclude : in VIOXX case, IM did not appeared immediately after first
intake but months after.
3. Adverse events are often reported for each event individually instead
of using composite outcomes that would increase statistical power.
Research for improving safety assessment and reporting of AE is still
needed.
4. New drugs are tested on selected populations with strict inclusion
criteria. After drug approval, real users of the new drug might differ
from experimental group. Post-marketing study in “real world” and
observational study can be useful for AE monitoring.
To finish, the highly covered VIOXX story is not an isolated case. Every
year about 2% of drugs are removed from the market (1). Recent examples
include diet drugs associated with cardiac valvular disease.
Reference
1. Friedman MA, Woodcock J, Lumpkin M, Shuren J, Hass A, Thompson L. The
safety of newly approved medicines. Do recent market removals mean there
is a problem? JAMA 1999; 28: 1728-34
Competing interests:
None declared
Competing interests: No competing interests
I read with great interest the article by Harlan Krumholtz and
colleagues enlightening the sad story of Vioxx and what we have learnt
from it.(1) This inspired me to add a few words of comment regarding the
use of analgesics in patients with cardiovascular (CV) and
gastrointestinal (GI) risk factors. In my opinion the rational choice for
such patients is the use of aspirin combined with a proton-pump inhibitor.
First, both coxibs and traditional NSAIDs should not be prescribed in
patients at higher CV risk. On the contrary, there is good evidence that
analgesic doses of aspirin (up to 1500mg) are associated with protection
from CV events.(2,3) Furthermore, aspirin dose or its higher lifetime use
is not significantly associated with hypertension(4) or renal
toxicity.(5,6) Importantly, a recent meta- analysis of 24 randomised
controlled trials found no evidence of dose- responsiveness for bleeds
over a wide range of doses (50 to 1500 mg/day).(7) Indeed, aspirin in
doses commonly used in practice, seems to have an excellent safety
profile.(8)
Second, recent evidence suggest that not only NSAIDs but also
acetaminophen can raise cardiovascular risk.(9) High acetaminophen use may
also increase the risk of hypertension(4) and a decrease of renal
function.(5) Interestingly, increased acetaminophen use has now been
linked to increased prevalence of asthma and chronic obstructive pulmonary
disease, and with lowered lung function.(10) Surprisingly, a recent case-
control study showed that acetaminophen (>2 g per day) was associated
with a greater risk of GI perforation or bleed(11) and one cohort study
reported a dose-response relationship between acetaminophen and
dyspepsia.(12) It appears that regular use of acetaminophen is also
associated with symptoms of severe diverticular disease, particularly
bleeding.(13)
Lastly, compelling evidence suggests that both aspirin and other
NSAIDs are superior to acetaminophen for improving moderate-to-severe pain
in patients with osteoarthritis(14,15,16) and rheumatoid arthritis.(17)
Likewise, in acute pain states aspirin provides significant and more rapid
analgesia than acetaminophen.(18)
References
1. Krumholz HM, Ross JS, Presler AH, Egilman DS. What have we learnt
from Vioxx?
BMJ. 2007;334:120-3.
2. Antithrombotic Trialists' Collaboration. Collaborative meta-
analysis of randomised trials of antiplatelet therapy for prevention of
death, myocardial infarction, and stroke in high risk patients. BMJ
2002;324:71-86.
3. Johnson ES, Lanes SF, Wentworth CE 3rd, Satterfield MH, Abebe BL,
Dicker LW.A metaregression analysis of the dose-response effect of aspirin
on stroke. Arch Intern Med 1999;159:1248-53.
4. Forman JP, Stampfer MJ, Curhan GC. Non-narcotic analgesic dose and
risk of incident hypertension in US women. Hypertension 2005;46:500-7.
5. Curhan GC, Knight EL, Rosner B, Hankinson SE, Stampfer MJ.
Lifetime nonnarcotic analgesic use and decline in renal function in women.
Arch Intern Med 2004;164:1519-24.
6. Dubach UC, Rosner B, Sturmer T. An epidemiologic study of abuse of
analgesic drugs. Effects of phenacetin and salicylate on mortality and
cardiovascular morbidity (1968 to 1987) N Engl J Med 1991;324:155-60.
7. Derry S, Loke YK. Risk of gastrointestinal haemorrhage with long
term use of aspirin: meta-analysis. BMJ 2000;321:1183-7.
8. Fries JF, Ramey DR, Singh G, Morfeld D, Bloch DA, Raynauld JP. A
reevaluation of aspirin therapy in rheumatoid arthritis. Arch Intern Med
1993;153:2465-71.
9. Chan AT, Manson JE, Albert CM, Chae CU, Rexrode KM, Curhan GC, et
al. Nonsteroidal antiinflammatory drugs, acetaminophen, and the risk of
cardiovascular events. Circulation 2006;113:1578-87.
10. McKeever TM, Lewis SA, Smit HA, Burney P, Britton JR, Cassano PA.
The association of acetaminophen, aspirin, and ibuprofen with respiratory
disease and lung function. Am J Respir Crit Care Med 2005;171:966-71.
11. Garcia Rodriguez LA, Hernandez-Diaz S. Relative risk of upper
gastrointestinal complications among users of acetaminophen and
nonsteroidal anti-inflammatory drugs. Epidemiology 2001;12:570-6.
12. Rahme E, Pettitt D, LeLorier J. Determinants and sequelae
associated with utilization of acetaminophen versus traditional
nonsteroidal antiinflammatory drugs in an elderly population. Arthritis
Rheum 2002;46:3046-54.
13. Aldoori WH, Giovannucci EL, Rimm EB, Wing AL, Willett WC. Use of
acetaminophen and nonsteroidal anti-inflammatory drugs: a prospective
study and the risk of symptomatic diverticular disease in men. Arch Fam
Med 1998;7:255-60.
14. Lee C, Straus WL, Balshaw R, Barlas S, Vogel S, Schnitzer TJ. A
comparison of the efficacy and safety of nonsteroidal antiinflammatory
agents versus acetaminophen in the treatment of osteoarthritis: a meta-
analysis. Arthritis Rheum 2004;51:746-54.
15. Towheed TE, Maxwell L, Judd MG, Catton M, Hochberg MC, Wells G.
Acetaminophen for osteoarthritis. Cochrane Database Syst Rev
2006;(1):CD004257.
16. Zhang W, Jones A, Doherty M. Does paracetamol (acetaminophen)
reduce the pain of osteoarthritis? A meta-analysis of randomised
controlled trials. Ann Rheum Dis 2004;63:901-7.
17. Wienecke T, Gotzsche PC. Paracetamol versus nonsteroidal anti-
inflammatory drugs for rheumatoid arthritis. Cochrane Database Syst Rev
2004;(1):CD003789.
18. Seymour RA, Hawkesford JE, Sykes J, Stillings M, Hill CM. An
investigation into the comparative efficacy of soluble aspirin and solid
paracetamol in postoperative pain after third molar surgery. Br Dent J
2003;194:153-7.
Competing interests:
Dr. Pijak has received speaker fees and travel assistance from Fournier.
Competing interests: No competing interests
In my previous letter, the third statement was too simple and can be
improved:
- patients at high risk of a cardiovascular event should be taking
low-dose aspirin. When these patients need analgesia there is no real
gastrointestinal advantage to choose a selective cox-2 inhibitor above a
nonselective NSAID (nsNSAID) plus gastroprotection, i.e. proton pump
inhibitor or misoprostol. However, the increasing evidence that some
nsNSAID (but not selective cox-2 inhibitors) seriously interfere with
aspirin's beneficial effect on platelets has made this setting very
complex, and treatment should be assessed on a case-by-case basis.
Competing interests:
See above
Competing interests: No competing interests
This article is enlightening in its exposure of Merck policy.
However, in the current climate the science is in danger of being
forgotten altogether. My view:
- all nonsteroidal antiinflammatory drugs (NSAIDs) are 'dangerous'
but their main toxicity is in the gut.
- in most patients the absolute risk of a cardiovascular event is
dwarfed by the risk of an ulcer, bleed or perforation.
- patients at high risk of a cardiovascular event should be taking
low-dose aspirin, in which case the choice for a selective cox-2 inhibitor
(instead of a nonselective NSAID) is probably useless, i.e. will not
decrease risk to the gut.
- when studied dispassionately and disregarding legal and economic
considerations, the evidence for increased cardiovascular risk of
rofecoxib, and the level of this increased risk is not strong enough to
warrant a retraction of the drug.
- If present, the risk is mostly limited to doses above 25 mg/d.
- the assessment of benefits and risks of a drug should take place in
the target population. Patients with polyposis are not the current target
population, hence results from a placebo-controlled trial are not very
useful to guide practice, as the target population will most likely be
taking an NSAID.
Finally, as rheumatologist I am puzzled by the extent of the outrage
over 'excess cardiovascular deaths' caused by vioxx, but the shattering
silence over the fact that gastroprophylaxis is never on the menu for
patients taking low dose aspirin, even though many of these patients can
be regarded as having a high gastrointestinal risk profile.
I guess the gut is simply less sexy than the heart, and bleeding to
death less worrisome than cardiac arrest.
Maarten Boers
Ref.:
Boers M. NSAIDs and selective Cox-2 inhibitors: competition between
gastroprotection and cardioprotection. Lancet 2001;357:1222-3.
Competing interests:
I have been an advisory board member for Pfizer and Novartis in the past
Competing interests: No competing interests
What have we learnt? The pharmaceutical industry knows that we have
not learnt enough.
Physicians and the lay public have become justifiably suspicious of
the COX2's as well as NSAIDs, and desire an alternative. So just this
month, a smiling pharmaceutical representative revealed to me the new
great hope, lumiracoxib. As evidence, I was presented with a reprint of
the Target Trial, a "megatrial" published in a top tier journal (1). I was
not shown the accompanying editorial. Although the abstract and the
article are strictly correct in stating that an increased risk was not
shown, they skillfully neglect to point out that they did not show no
difference. This is a subtlety which many busy physicians will overlook.
They will also likely overlook the fact that the study was intentionally
designed to have too few cardiac events to have a significant likelihood
of showing danger. And they will commonly overlook the 95% confidence
intervals which show a significant possibility of lumiracoxib inceasing
cardiac risk by as much as 8-fold for certain groups.
Major journals must do more than provide editorials to counteract the
flagrant optimism of clinical trial reports, because too many physicians
do not routinely read them. Journals must ensure that the titles and
abstracts of articles accurately reflect the reality of what is shown by
the data.
Actually, we learnt that long ago. It is time for our journals to act
accordingly.
1. Farkouh et al. Comparison of lumiracoxib with naproxen and
ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event
Trial (TARGET), cardiovascular outcomes: randomised controlled trial.
Lancet. 2004 Aug 21-27;364(9435):675-84.
Competing interests:
None declared
Competing interests: No competing interests
Hindsight is beautiful thing is it not?
The article by Krumholz et is all very well written but we should not forget
that medical journals like NEJM and JAMA and Annals of internal
medicine should step forward and take their share of blame for publishing
these papers and I strongly feel that issuing corrective statement is not
enough. As far as I understand, there is a peer review system in place and I
seriously hope the people who review these articles are expert in their
field and able to spot flaws and loopholes in studies which sound dodgy
in their design and analysis of results. There is very little benefit in
issuing corrective statement few years down the road when every thing is
done and dusted and case almost settled.
Medical and research community has to look at itself in this case and
share the blame as much as Merck should do.
Competing interests:
None declared
Competing interests: No competing interests
The Vioxx case has harmed thousands of people across the globe with
its adverse cardiovascular events as has been established by published
studies. Yet, it has done a world of good to millions of people who have
now been saved! The case serves as a stern warning to pharmaceutical
companies as well as medical researchers who are launching drugs without
adequate safeguards.
It is unbelievable that the company did not realise the possibility
of adverse cardiovascular effects during the course of the drug's
evolution. Krumholz et al have clearly established that critical data on
the drug's toxicity was obscured.
One hopes that greed does not convert the healthcare industry from
being a saviour to a killer. Every practising physician, clinical
researcher, medical representative, marketing manager and owner of
pharmaceutical companies should constantly remember that each one of them
could potentially be at the receiving end of a physician's prescription.
Let him not forget that in such a situation he will have little choice but
to swallow the bitter pill!
Competing interests:
None declared
Competing interests: No competing interests
Re: On Selective Learning
Merck’s lawyer writes that he “will not offer [his] views,” as he
offers his views in his critique of our article. Unfortunately his
letter, which he claims is a “correction” of our article, misrepresents
Merck’s conduct and the results of Merck’s drug trials.
Merck included some data from the prostacyclin study in its
regulatory submission but excluded the most important part – the non-Merck
authors’ conclusion that the “inhibition of urinary PGI-M by Vioxx implies
a major role for Cox-2 in the vascular biosynthesis of prostacyclin in
humans.”
Furthermore, the primary FDA reviewer responsible for reviewing the
data concluded in 1999 that Merck’s pre-market Vioxx trials did contain
important signals of cardiovascular risk when he wrote:
1. Vioxx caused vascular-renal adverse events, i.e., hypertension-
and edema-type, serum creatinine increased, hyperkalemia, and to a lesser
degree proteinuria in a dose-dependent manner.
2. The vascular-renal safety profile of Vioxx is clearly distinguishable
from placebo, and is qualitatively similar to other NSAIDS.
3. The aforementioned adverse events occur at a higher rate with VIOXX at
50 mg, than with other NSAIDS at their recommended dosage. However,
whether that will translate into clinically significant differences in
vascular-renal morbidity cannot be determined from the current
osteoarthritis clinical database.
[http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4090B1_06_G-FDA-Tab-
D-2.pdf]
Another FDA review noted that “The data seem to suggest that in 6 -
week studies, thromboembolic events are more frequent in patients
receiving rofecoxib than placebo but do not show a clear dose response
relationship with rofecoxib.”
[http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4090B1_05_F-FDA-Tab-
D-1.pdf]
Both reviewers observed that the studies were not large enough to
find an effect since they were short term, excluded high risk patients and
failed to include tests designed to detect CV events. For example, Merck
failed to perform exit EKGs. These studies were also underpowered. Power
is a function of the number of expected events in a trial, not the total
number of patients studied. As the manufacturer, Merck had the
responsibility to follow up and warn about this early signal of harm.
We did not suggest that Merck failed to adjudicate CV events in
Vigor. Merck, however, did manipulate the adjudication process. During
VIGOR, but after Merck personnel were unblinded to overall results, Merck
deleted 21 cardiovascular diagnoses from the Standard Operating Procedure
list of events eligible for adjudication (SOP for all Vioxx trials).
Deletions included CHF, pulmonary edema and a variety of new EKG changes.
These changes were made on December 29, 1999 one week after the external
safety board told Merck to perform an analysis of CV events for this
particular trial. At that time Merck had no plans to analyze any of the
CV data from VIGOR or any other individual Cox-2 trial. Merck pre-dated
the change to October 3, 1999.
In regards to the Vigor DSMB’s chairman’s ownership of Merck stock,
the article simply pointed out the potential for a meaningful conflict of
interest and the fact that such stock ownership violates Merck’s own
guidelines, which we cited in the article (print citation #10). Those
guidelines say, “DSMB members should not have such a substantial financial
investment in Merck or in any of our competitors that their independence
would be questioned. All members should issue a periodic report describing
potential conflicts of interest. The DSMB chairman should review these
potential conflicts prior to each meeting, and forward them to the DSMB
chairman along with the status report.” The chairman also signed a
contract with Merck on March 6, 2000 (11 days prior to end of the Vigor
trial) to consult on the marketing and research and development of COX-2
agents including Vioxx:
The consultant will provide confidential advice, counsel, and
assistance in the development, planning and execution of commercial and
scientific initiatives related to Merck’s COX-2 Inhibitor program (the
“Consulting Service”). The Consulting Services may cover topics including,
but not limited to, market development, strategic product planning, and
educational activities as well as the design and the conduct of the
clinical and preclinical development program. (Ref. 12 in our article)
Readers should be able to decide whether the stock ownership and
consulting contract constitute a conflict of interest, and Merck should
allow readers that opportunity, rather than objecting to the disclosure of
this information.
Merck’s lawyer asserts that we omitted information from Dr. Curfman’s
deposition conducted after the submission of our article and that this
information supports Mayer’s assertion that Dr. Curfman, “…knew of the
post-cutoff data from its publication in August 2001, in the very JAMA
article the authors cite.” Mr. Mayer conflates access to the “full data”
with the issue of whether or not the data should have been included in the
NEJM VIGOR paper. The latter question centered on knowledge of different
cut off dates for analyzing CV and GI events and whether or not the “full
data” was available to Merck when they submitted the Vigor paper to the
NEJM. The NEJM authors reasonably believed that the late data was
unavailable when the VIGOR paper was submitted or that this data fell
outside of a scientifically justifiable “cut off.” Neither was the case.
Dr. Curfman’s testimony directly contradicts Merck’s lawyer’
assertion:
Q. Doesn't that suggest to you that there was evidence that the
sponsor [Merck] had on CV issues that were not in the paper that were in
hand before the paper was published?
A. No.
Q. So, you read this sentence to conclude that all this evidence came
to Merck after the paper was published?
A. It doesn't specify when they had the data, and I don't think that
these authors would know. They [the authors of the JAMA article] are not
authors of the VIGOR article. They had no access to the primary data. They
weren't involved in the study. They're writing a commentary article here.
They are commentators, they are not authors, and this is not our Journal
[NEJM].
Dr. Curfman repeatedly told Merck’s lawyer’s that their client had
played “hide and seek” with the data. Merck initially designated several
lines of this deposition “confidential,” claiming it contained trade
secrets, but in correspondence Merck told us that they withdrew their
confidentiality claim. We have made Dr. Curfman’s deposition available to
the public [http://www.vioxxdocuments.com/browse.php] so readers can make
their own evaluation of Dr. Curfman’s knowledge. Merck complains that we
omitted key information that was available in this deposition but, but the
final version of our paper was submitted to BMJ, and the issue went to
press, before the deposition even occurred. If Merck’s lawyers believe we
misrepresented the facts surrounding their handling of Vioxx, they should
lift the veil of secrecy they have placed on their data and documents and
make them accessible on the web as the tobacco companies have done. The
drug is off the market; the only “trade secrets” are marketing
practices and methods of data manipulation. The medical community has
much more to learn from these documents.
Competing interests:
Dr. Egilman has served as an expert witness at the request of plaintiffs in the Vioxx litigation. Mr. Presler has served as a consultant at the request of plaintiffs in the Vioxx litigation.
Competing interests: No competing interests