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Sequestered Evidence and the Distortion of Clinical Practice Guidelines

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Abstract

As a result of the growth of evidence-based practices across the world, health-care providers and policymakers in the United States, United Kingdom, and Europe have established institutes such as the United Kingdom’s National Institute for Health and Clinical Excellence (NICE) to produce clinical guidelines that physicians are asked to use in their daily practice. This article discusses how the withholding of clinical trial information by pharmaceutical companies and academic researchers affects the reliability of clinical guidelines. It first offers a case study analysis of the U.K. drug regulator’s failure to prosecute GlaxoSmithKline, manufacturer of the bestselling antidepressant Seroxat (manufactured as Paxil in North America), for withholding information on the safety of Seroxat from regulators. It next examines the idea of a “Sarbanes- Oxley for Science,” a recent proposal that seeks to introduce legislation forcing companies to disclose clinical trials that have indeterminate or negative results. Legislation such as Sarbanes-Oxley for Science would solve some problems with the withholding of data, but not all. Until practitioners and policymakers address the political and legal barriers preventing full access to clinical trial data for all medical treatments, the ideals of evidence-based practice will remain elusive.
203
Li ns ey M cG oe y
Sequestered Evidence and
the Distortion of Clinical
Practice Guidelines
Institute for Science, Innovation and Society, Saïd Business School, University of Oxford, Park End
Street, Oxford, OX1 1HP, United Kingdom.
E-mail: linsey.mcgoey@sbs.ox.ac.uk.
The author wishes to thank Catherine Will for comments dur ing the course of writing, and Gerry
McGoey for raising the idea of a “Sarbanes-Oxley for Science.
Perspectives in Biology and Medicine, volume 52, number 2 (spring 2009):203–17
© 2009 by The Johns Hopkins University Press
ABSTRACT As a result of the g rowth of evidence-based practices across the
world, health-care providers and policymakers in the United States, United Kingdom,
and Europe have established institutes such as the United Kingdom’s National Institute
for Health and Clinical Excellence (NICE) to produce clinical guidelines that physi-
cians are asked to use in their daily practice.This article discusses how the withholding
of clinical trial information by phar maceutical companies and academic researchers af-
fects the reliability of clinical guidelines. It first offers a case study analysis of the U.K.
drug regulator’s failure to prosecute GlaxoSmithKline, manufacturer of the bestselling
antidepressant Seroxat (manufactured as Paxil in North America), for withholding in-
formation on the safety of Seroxat from regulators.It next examines the idea of a “Sar-
banes-Oxley for Science,” a recent proposal that seeks to introduce legislation forcing
companies to disclose clinical trials that have indeterminate or negative results.
Legislation such as Sarbanes-Oxley for Science would solve some problems with the
withholding of data, but not all. Until practitioners and policymakers address the polit-
ical and legal barriers preventing full access to clinical trial data for all medical treat-
ments, the ideals of evidence-based practice will remain elusive.
IT IS RARE FOR A SCHOLARLY BOOK from a professor of public health to make
the book pages of Vanity Fair magazine. In May 2008, the magazine that typ-
ically celebrates consumer luxuryaligning itself, however inadvertently, with U.S.
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Linsey McGoey
Perspectives in Biology and Medicine
corporate interests—featured a number of recent books that have criticized the
uglier side of American enterprise. One of those books was David Michaels’s
Doubt Is Their Product (2008), which details the many ways that scientists and cor-
porate lobbyists manipulate and distort scientific evidence in order to paint their
products—from tobacco to pharmaceutical drugs such as Vioxx—in a more
favorable light.
Michaels, a professor of Public Health at George Washington University and
a former U.S.Assistant Secretary of Energy for Environment, Safety, and Health,
has been trying for years to shed light on the problem I discuss below: the ten-
dency of pharmaceutical companies to withhold negative clinical trial results
from both the public and regulatory bodies in the United States and the United
Kingdom. In recent work, Michaels suggests developing a “Sarbanes-Oxley for
Science.” Sarbanes-Oxley is the securities legislation that was developed in the
wake of the Enron and WorldCom scandals to help prevent company executives
from distorting or hiding financial statements from regulators. Michaels believes
that a Sarbanes-Oxley for Science could be a solution to the problem of selec-
tive trial disclosure (Michaels 2006, 2008).
In this article, I discuss the strengths and weaknesses of the idea of a Sarbanes-
Oxley for Science by drawing on a case-study analysis of the controversy over
whether GlaxoSmithKline (GSK) withheld data on the safety of Seroxat, its best-
selling selective serotonin reuptake inhibitor (SSRI) antidepressant drug, from
government regulators in the United Kingdom. I suggest the main benefit of a
Sarbanes-Oxley for Science is that it helps to illuminate existent inadequacies in
the regulation of pharmaceutical drugs.The disadvantage of the proposal is that it
does not take into account something illuminated by the SSRI controversy: mere
disclosure of data alone does not ensure action on the part of regulatory author-
ities. The financial dependence of U.K. regulators on the pharmaceutical indus-
try may hinder them from acting swiftly on evidence of adverse effects when they
are disclosed. Until this financial relationship is addressed, the ability of physicians
and patients to access clinical trial data from regulators or industry—which is
essential for the evidence base of treatment guidelines—will remain limited.
This article draws on an analysis of medicines legislation, documents released
by regulatory bodies in the United Kingdom and United States, and in-depth
interviews with 20 policymakers, psychiatrists, epidemiologists, and regulators in
the United Kingdom who have been involved with efforts to determine the
safety of SSRIs.
Ac ce ss t o RC T Da ta a nd t he D is to rt io n
of Evidence-Based Guidelines
The emergence of evidence-based practices in the United States, United King-
dom, and elsewhere has led to the development of institutions that produce evi-
dence-based guidelines (Heimer, Coleman, and Culyba 2005; Timmermans
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2005).The U.K.s National Institute for Health and Clinical Excellence (NICE)
is the main body in England and Wales responsible for producing such guide-
lines. According to the NICE Web site, all staff members working within the
National Health Service are expected to follow NICE guidance on a given treat-
ment. If their health-care providers do not follow NICE guidance, patients are
urged to register a formal complaint (NICE 2006).
In theory, and in the view of practitioners I have spoken with, there should
be a close degree of coordination between NICE, which produces national
treatment guidelines, and the United Kingdom’s Medicines and Healthcare
Products Regulatory Agency (MHRA) which is responsible for the licensing
and post-market surveillance of all medicines and medical devices in Britain.
This is because the MHRA, as the government drug regulator, has a statutory
duty to protect U.K. consumers from unsafe treatments. Clinicians assume that
the MHRA and NICE are working in concert to ensure that treatments rec-
ommended in NICE guidelines have passed through rigorous safety standards
safeguarded by the MHRA. As the case below reveals, however, much conflict
exists between NICE policymakers and MHRA staff, conflict that in the case of
SSRIs prevented NICE policymakers from accessing clinical trial data necessary
for formulating reliable guidelines.
SSRI Safety and Regulatory Weaknesses at the MHRA
SSRI antidepressants were first marketed in the United Kingdom and the
United States in the late 1980s and early 1990s.These antidepressants, which in-
clude Zoloft, Sexorat, and Prozac, are among the best-selling drugs ever pro-
duced. In the years leading up to expiration of Prozac’s patent in 2001, the drug
generated approximately U.S.$2.6 billion for Eli Lilly annually, a full quarter of
the company’s total revenues (Shook 2000). Despite their popularity, some ob-
servers have suggested that SSRIs might lead to suicidal reactions in some users,
something hard to determine because it is hard to know whether it is the drug
or underlying depression that has led a patient to commit suicide (McGoey
2007; Nutt 2003). One way to answer this question is to examine the random-
ized controlled trial (RCT) data testing the efficacy of SSRIs, to see whether
there are more suicidal events recorded on the SSRI arms of trials than on the
comparator arms. The problem, however, is that SSRI manufacturers such as
GSK are believed to have withheld RCT data where more suicidal ideation oc-
curred on the SSRI arm of trials.
In the spring of 2003, the MHRA directed its Committee on Safety of Med-
icine (CSM), a working group mandated to advise the MHRA on all drug
licensing, to address the question of SSRI safety. In December 2003, as a result
of the CSM’s recommendations, the MHRA issued a contraindication against
the use of all SSRIs except Prozac in children.A year later, in December 2004,
the regulator advised NICE to revise its clinical guidelines for the use of anti-
depressants in the treatment of depression across all age groups.The actions taken
Sequestered Evidence and the Distortion of Guidelines
spring 2009 • volume 52, number 2 205
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Perspectives in Biology and Medicine
by British regulators contributed to FDA hearings on the safety of SSRIs in
2004. As a result, the FDA mandated SSRI manuf acturers to add a “black box”
to indicate the increased risk of suicidal thoughts and behavior in children and
adolescents being treated with SSRIs (FDA 2004).
The decision to issue a contraindication on the use of SSRIs in children
stemmed from a series of actions that drew attention to the possibility of illegal
behavior at companies such as GSK. Questions surrounding GSK emerged in
the spring of 2003, when the company submitted a dossier to the MHRA’s SSRI
expert working group containing previously undisclosed data from Studies 329
and 377, two clinical trials carried out on adolescents in 11 countries in the mid-
1990s. Data from these studies indicated a lack of evidence of the efficacy of Ser-
oxat (manufactured as Paxil in North America) in adolescents, as well as in-
creased risk of suicidal reaction over placebo. The MHRA later noted of the
studies:“The lack of evidence of efficacy, together with evidence of a causal asso-
ciation between Seroxat and suicidal behaviour, meant that the overall benefit-
risk balance could not be positive for use in under-18s. At the time, there were
an estimated 7-8,000 under-18s being treated with Seroxat in the UK” (MHRA
2008a).
A confidential GSK document, dated October 1998 and later circulated on
the Internet, suggests GSK intentionally withheld Studies 329 and 377 from reg-
ulators. The document, entitled “Seroxat/Paxil Adolescent Depression: Position
Piece on the Phase III Clinical Studies, stipulates that company representatives
should be cautious in disseminating the results of Study 329 and 377, stressing
that “it would be commercially unacceptable to include a statement that efficacy
had not been demonstrated, as this would undermine the profile of paroxetine”
(GSK 1998; Kondro 2004).The document states:
Study 329 (conducted in the US) showed trends in efficacy in favour of Seroxat/
Paxil across all indices of depression. However, the study failed to demonstrate a
statistically significant difference from placebo on the primary efficacy measures.
...Data from these 2 studies are insufficiently robust to support a label change and will
therefore not be submitted to the regulatory authorities. (GSK 1998, emphasis added)
GSK’s handling of Studies 329 and 377 led to legal actions in the United States,
where the former New York Attorney General Eliot Spitzer launched a lawsuit
in August 2004 accusing GSK of consumer fraud by depriving consumers and
doctors of information necessary to make informed decisions (Lancet 2004).
GSK later settled out-of-court with Spitzer, refusing an admission of wrong-
doing, but agreeing to pay a fine of $2.5 million.
In October 2003, MHRA launched an investigation into GSK to determine
why the company had not submitted the data from Studies 329 and 377 at an
earlier time, as they were seemingly obligated to do by U.K. Medicines Act 1968.
This Act makes withholding data relevant to a drug’s risk-benefit profile an ille-
gal offence subject to imprisonment and unlimited fines. Five years later, in
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March 2008, the MHRA announced the culmination of its inquiry. The agency
stated that, although GSK had acted unethically by not submitted clinical trial
data which revealed Seroxat was more harmful than placebo in children, the reg-
ulator did not have the legal means to prosecute the company (MHRA 2008b).1
The U.K. Medicines Act is not as effective in enforcing the disclosure of clinical
trial data as regulators had previously assumed. In conducting their inquiry, the
MHRA retained independent legal counsel, who advised the agency that loop-
holes in the Act rendered the legislation “sufficiently unclear as to make a crim-
inal prosecution impossible” (MHRA 2008a)
Throughout its history, the MHRA has never once prosecuted a company for
withholding clinical trial data from regulators. This fact, plus the observation that
it took the MHRA nearly five years to determine that the legislative governing
drug licensing was itself ineffective in prosecuting the failure to disclose data, raises
a number of questions. First, does the agency have an interest in not prosecuting
companies? Second,what steps can or should be taken to improve legislation gov-
erning the disclosure of trials, in the United Kingdom and internationally?
Re gu la to ry F ai lu re a t th e MH RA ?
Institutional Obstacles to Policing Industry
Since 1989, the MHRA has been 100% funded by the pharmaceutical industry
for the service of licensing medicines (Abraham 1995, 2002; Breckenridge and
Woods 2005). Sociologists such as John Abraham have suggested that this finan-
cial arrangement has prevented regulators from acting in the interest of patients
over pharmaceutical companies. In line with work by Abraham on the MHRA’s
handling of drugs such as Halcion and Opren (Abraham 1994; Abraham and
Sheppard 1999), I suggest this funding structure may have hindered the MHRA
from demanding pertinent clinical trial from SSRI manufacturers when safety
problems with SSRIs first emerged.
I met with Kent Woods, the MHRA’s Chief Executive Officer, for an inter-
view in January 2007—one year before the MHRA announced the culmination
of its investigation into GSK. During our interview, I asked about the status of
the inquiry. He stressed that the MHRA has devoted many resources to the case:
This is a long and complex investigation which is nearing its conclusion.We
have given a great deal of resources and efforts to doing this. I obviously can’t
say much about it, because we are at the moment waiting for analysis of council’s
opinion. And the decision has not been made as to whether this goes to court or
not. But it has been a very large and intensive exercise from our point of view. I
can tell you that we have obtained and examined over a million pages of docu-
mentation: that is a measure of the scale and the complexity and resources used
in this case.
Sequestered Evidence and the Distortion of Guidelines
spring 2009 • volume 52, number 2 207
1The legal complexities of the MHRA’s decision not to prosecute GSK are further explored in
McGoey and Jackson (2009).
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Woods’s insistence on the complexity of the case makes the MHRA’s eventual
announcement all the more surprising: in examining millions of pages of docu-
mentation, the MHRA failed to grasp there were inadequacies within the leg-
islative framework that would render a prosecution difficult. Another question is
why it took the MHRA so long to deter mine Seroxat’s suicide risk—later re-
vealed in both children and adults—in the first place.
The MHRA launched its investigation into GSK in the fall of 2003, after the
company submitted Studies 329 and 377 to the MHRA’s 2003–2004 expert
working group on SSRIs. This working group was the sixth time, over more
than ten years, that the MHRA had convened a committee to investigate SSRI
safety. During the MHRA’s 2003–2004 inquiry, the working group wrote to all
companies that manufactured SSRIs requesting clinical trial data related to sui-
cidal events. Companies were asked to provide a variety of data, including sum-
maries of all clinical trials, whether published or not, as well as case narratives of
any suicides that occurred during trials.After having analyzed the summary reports
provided by GSK, and not all available individual data, the MHRA expert work-
ing group concluded:
These data show no conclusive evidence that adult patients exposed to paroxe-
tine are at increased risk of suicidal events compared with patients exposed to
either placebo or another active drug in any of the indications investigated.
However, the data are consistent with the possibility of an increased risk of suicidal events
in patients with depression exposed to paroxetine compared to placebo. (MHRA 2004,
p. 82, emphasis added)
The MHRA’s report went on to note that:
The meta-analysis has been restricted to data provided from trials conducted by
the MA Holder [GSK], and has not included any data from other randomised
trials conducted by other groups or published studies. Consequently it is not a for-
mal meta-analysis of all available data. Whilst the results provide no clear evidence
of an increased risk, the range of risk ratios included within the 95% confidence
intervals are consistent with the possibility of a small increased risk of suicidal
events for patients exposed to paroxetine compared with placebo. (pp. 82–83,
emphasis added)
Despite the fact that the 2003–2004 working group was the sixth time the
MHRA convened a committee to investigate the possibility of suicidal risk, the
working group did not scrutinize the individual patient data held by GSK,
despite the fact that, as numerous epidemiologists and psychopharmacologists I
have spoken to have reiterated to me, the analysis of individual data is vital for
determining things such as how reliably endpoints have been recorded. Nor did
it attempt, in the words above, a more formal meta-analysis when initial findings
revealed the possibility of a small increase of suicidal events.
Had the MHRA insisted on another meta-analysis at that time, it may have
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detected what GSK later admitted: a re-analysis of the company’s own data, car-
ried out by GSK at the behest of the FDA, revealed a statistically significant risk
of suicide over placebo in adults. As the British Medical Journal reports, GSK ad-
mitted in 2006 that clinical trial evidence in its possession for over a decade indi-
cated that patients prescribed Seroxat were six times more likely to attempt sui-
cide than those given a placebo: “GlaxoSmithKline announced last week that
they had found an increase in suicidal behaviour in adults taking paroxetine
(Paxil/Seroxat) compared with Placebo. . . .The Glaxo study confirms the sug-
gested link between suicidal behaviour and antidepressants in adults” (Lenzer
2006, p. 1175).
Following this disclosure from GSK, attention once again turned to the
MHRA’s failure to detect such evidence during its previous inquiries into the
safety of SSRIs. During our 2007 interview, I asked Woods why, in his view, the
MHRA had not detected the increase earlier. He replied:
We are talking about events that typically were occur ring at a frequency of 1%
or less. And I think from memory—and this is from memory—the point esti-
mate in the meta-analysis that Glaxo were describing was an incidence of 0.05%
which went up to something like 0.33%. Now, firstly, the absolute figures make
it much clearer what the scale of change is.And secondly, you have to ask the
question, what is the contr ibution of random noise? In other words, six-fold
tells you nothing about the statistical significance of that change.And it tells
you nothing about the absolute scale of that change. If we’re talking about event
rates that were occurring at a frequency of less than half of 1%, you can see why
meta-analyses may change slightly from time to time depending on what the
events of importance of the analysis are. Are you talking about suicides? From
memory there were no suicides in any of the trials. Are you talking about
attempted suicides? Suicidal ideas? And whichever endpoint combination you
use, you’ll get a slightly different answer.
Woods’s comment about statistical issues is correct, and at first glance seems a
justifiable response.But the comment,and particularly his suggestion that the in-
creased suicidality exhibited on the Seroxat arms of the trials may have been
small enough to explain the MHRA’s non-detection, raises a number of ques-
tions. While it is true that the increase is not large, it was significant enough for
GSK to circulate a letter to health-care practitioners advising them that a re-
analysis of existent data had raised concerns with the company’s own product:
“In the analysis of adults with MMD [mild-to-moderate depression] (all ages),
the frequency of suicidal behaviour was higher in patients treated with paroxe-
tine compared with placebo (11/3455 [0.32%] versus 1/1978 [0.05%].This dif-
ference was statistically significant” (GSK 2006, emphasis added).
Woods suggests that with every new meta-analysis of individual RCTs,results
can differ slightly, and this heterogeneity makes it difficult to detect risks.While
this is certainly plausible, it raises a number of further questions. The MHRA
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spring 2009 • volume 52, number 2 209
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chose to license Seroxat based on the same data Woods later suggested was insuf-
ficient for determining the risks of the drug. In some ways, this is reasonable:sui-
cide is a rare endpoint, and when endpoints are rare, one requires a large group
of subjects to determine the statistical significance of results. But implicitly,
Woods’s comment raises a number of questions. He notes, for example, that “you
have to ask the question, what is the contribution of random noise? In other
words, six-fold tells you nothing about the statistical significance of that change.
And it tells you nothing about the absolute scale of that change.” If “random
noise” can bias understandings of the adverse effects of a treatment, it can equally
affect interpretations of a treatment’s efficacy. By noting the difficulties in deter-
mining the adverse effects of drugs, Woods inadvertently impugns the very
methods relied on by regulators in determining drug efficacy in the first place.
NICE and the Legal Barriers to Accessing
Cl in ic al T ri al D at a
In order to create clinical practice guidelines, NICE commissions policy recom-
mendations from various specialist bodies. In 2003, NICE asked the United
Kingdoms National Collaborating Centre for Mental Health (NCCMH) to
produce recommendations for the treatment of depression in children and ado-
lescents. As Tim Kendall, co-director of the NCCMH, described to me during
two interviews which took place in February 2005 and December 2006, the
NCCMH staff in charge of the project, Kendall and Craig Whittington, set
about producing their recommendations by examining a variety of evidence
useful in formulating guidelines, including case reports, “gray literature” such as
media or governmental reports, and RCTs.
One of Kendall’s aims was to determine whether SSRI antidepressants are
useful in the treatment of depression in children and adolescents.To investigate
this, NCCMH staff wrote to all SSRI manufacturers requesting unpublished and
published RCT data testing the safety and efficacy of SSRIs in children. Ac-
cording to Kendall, the companies he approached told him that no additional
data existed beyond clinical trial information that had been published in med-
ical journals. Later, however, Kendall was contacted by the MHRA, and told the
MHRA was planning to post six unpublished RCTs testing SSRIs in children
on their Web site.This was the first he learned of the existence of additional data,
as well as the first time the MHRA has ever chosen to publicly release unpub-
lished clinical trial data (Kendall and McGoey 2007).
Based on a previous meta-analysis of published RCT data, Kendall’s team had
been planning to recommend SSRIs as safe for use in children. When they
learned of the new data available on the MHRA’s site, they undertook another
meta-analysis to examine the unpublished data in conjunction with published
trials, and found that,when the unpublished data were added, the apparent effec-
tiveness seen with the published trials disappeared (Kendall and McGoey 2007).
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At first, the MHRA’s decision to post trials on itsWeb site suggested that the
agency was invested in helping ensure NICE had full access to trial data. My in-
terview with Woods, however, suggests this may not have been the case:
LM: Would you like to see a move to a system where NICE had access
to the same data as the MHRA?
KW: No.
LM: Why not?
KW: It’s important to understand firstly what NICE is there for. NICE
is an NHS organization. Its job is to give advice and guidance to
the NHS. I mean, the NHS is just a very large health maintenance
organization.We have a statutory responsibility to the nation as a
whole, and therefore our remits are somewhat different. The second
thing is that is it far preferable that we are able to communicate to
NICE at a confidential level, so that NICE is able for instance to
organize their work programme, and to plan when a product is
likely to come up for appraisal, than NICE having access to the
raw data that we see.
LM: As a former clinician yourself, as an epidemiologist, are you worried
about what people like Chalmers have talked about, which is the
general integrity of evidence bases.
KW: I know one of the things that bothers Iain [Chalmers]. And maybe
this is what he has referred to. That companies submit to NICE
the data they chose to submit.They submit to us, under legal obli-
gation, all the data they have. And so, in a way, NICE is working
at a disadvantage.2
Until recently, there has been little attention to the legal inability of bodies such
as NICE and NCCMH to access clinical trial data and to how that affects the
development of clinical practice guidelines. Though a handful of observers—
such as Iain Chalmers, one of the founders of the U.K. Cochrane Collabora-
tion—have struggled for a more than two decades to draw more attention to the
problem of underreporting of trial data (Abraham and Sheppard 1999; Chalmers
1990, 2006; Jørgensen, Hilden, and Gøtzsche 2006; Medawar and Hardon 2004;
Roberts, Li Wan Po, and Chalmers 1998), their efforts have remained ineffective.
In the last few years, this seemed to be changing.The pharmaceutical indus-
try appeared willing to be more open, with various companies insisting they
would establish voluntary databases of all clinical trial data. This initiative was
bolstered by claims from the U.S. and U.K. gover nments, such as the U.K.
Labour Party’s insistence, in its 2005 election manifesto, that it would pass laws
to ensure industry complied with the need to register trials. Since then, how-
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spring 2009 • volume 52, number 2 211
2This excerpt is quoted and discussed further in McGoey (n.d.) and McGoey and Jackson (2009).
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ever, it has been apparent these initiatives have failed to produce many practical
changes. As Kendall said to me:
The Labour government stated in their manifesto for the last election that they
would make it mandatory for drug companies to publish their trials. It has not
become mandatory in any meaningful way. Indeed, although the ABPI [Associa-
tion of the British Pharmaceutical Industry] asserts that drug companies do pub-
lish all completed trials, it is impossible to prove whether or not this is happen-
ing. Eli Lilly do list large numbers of trials on their website, many of which have
not been published. . . . However, there are a growing number of trials referred
to as “ongoing” and some of these have been “ongoing” since 2000. Perhaps
“ongoing” has now replaced “unpublished”! (Kendall and McGoey 2007, p. 137)
In February 2008, the United Kingdom’s Health Minister admitted that E.U.
legislation prevented the government from delivering on the Labour Party’s 2005
election promise of forcing companies to publicly disclose all clinical trial data
(Rose 2008).This revelation from the government has cemented the view that,
despite pharmaceutical companies’ explicit willingness to post trials, more legis-
lative force is needed to legally command companies to disclose clinical trial data.
Such a view is encapsulated by recent calls for a Sarbanes-Oxley for Science.
To wa rd s a Sa rb an es -O xl ey f or S ci en ce ?
As mentioned earlier, the phrase “Sarbanes-Oxley” refers to the U.S. securities
legislation passed in the wake of the Enron and Worldcom scandals in the early
2000s. At Enron and Worldcom, a series of frauds perpetrated by company exec-
utives prevented regulator and stockholders from grasping the true financial
worth of the companies, something that eventually led to the companies’ bank-
ruptcies. The fraud committed at Enron,Worldcom, and other companies led to
the passing of the Sarbanes-Oxley Act of 2002, the largest overhaul of corporate
governance securities legislation since the Securities Exchange Act of 1934
(Heminway 2003;Paredes 2003). Sarbanes-Oxley enforces a number of new reg-
ulations, such as the need for the chief executive officer and chief financial offi-
cer of every publicly listed company to verify the truthfulness of a company’s
financial certificates, risking criminal penalties if found guilty of fraud.
Scholars such as David Michaels (2006) have suggested that developing par-
allel legislation—a “Sarbanes-Oxley for Science”—would help tackle the prob-
lem of the underreporting of clinical trials at places such as GSK:
When the Enron and WorldCom scandals were revealed, the executives of those
firms claimed that they were unaware of the accounting misrepresentations in
which their companies were engaged. . . . At present, there is virtually no over-
sight or independent review of corporate decisionmaking as it relates to the
sequestration of scientific data. An important lesson of the accounting scandals
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is that responsibility must be linked with accountability; this should apply to sci-
entific as well as financial data. (p. 16)
Developing a Sarbanes-Oxley for Science, Michaels argues, would help to ensure
that scientific data are disclosed in the same manner as financial certificates at-
testing to a company’s financial status. He raises the proposal in the foreword to
a recent special issue of Law and Contemporary Problems. Details of how such an
initiative would work are nascent at this stage, but Michaels suggests that, first,
the legislation “would require corporations to designate a person responsible for
reporting the results of studies undertaken by the firm” (p. 16). Second, the leg-
islation would work to ensure access to the raw data—anonymized data on pa-
tients participating in trials—in both industry-sponsored and publicly funded
clinical trials.
The idea of a Sarbanes-Oxley for Science has considerable merit for drawing
attention to the problem of selective trial disclosure. But some caveats can be
raised.The first is simply its feasibility. Numerous observers have pointed out that
complying with the or iginal Sarbanes-Oxley Act has been burdensome for com-
panies, particularly small to mid-sized ones—to the extent that some are calling
for the Act to be repealed (Economist 2005). It is possible that U.S. governmen-
tal authorities will refrain from introducing legislation that might hinder the
competiveness of industries already constrained by the burden of the original
Sarbanes-Oxley. Second, Michaels’s equation of increased legislation with
increased transparency does not address something apparent from sociological
studies of transparency: often an commitment to transparency masks efforts to
conceal the very information a company is meant to be disclosing; a commitment
to transparency often creates a simultaneous need for discretion (Barry 2006;
Best 2007; Hood and Heald 2006).
In line with this point, Michael Power (2005), a theorist of risk and account-
ing, suggests there is no proof that“reactively created certification and disclosure
regimes” such as Sarbanes-Oxley have any capacity to create more regulatory
compliance. At times, regimes of disclosure may have the unintended effort of
making information less accessible, in part through increasing the complexity of
how information is disclosed. Thus, efforts to increase transparency through
measures such as Sarbanes-Oxley may reinforce the obscurity of corporate prac-
tices, in part because the onus to record transactions with “documentary preci-
sion, another label for the tick-box approach, is a feature of an institutional envi-
ronment in which agents must develop strategies to avoid the possibility of
blame” (Power 2005, p. 16; see also Hutter and Power 2005).
This last point helps to explain why proposals such as a Sarbanes-Oxley for
Science—while a useful step—should be treated with caution. Often the
response to a controversy over the safety of a pharmaceutical drug is to demand
more transparency on the part of companies thought to have withheld data. But,
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as the example above of the MHRA’s handling of SSRIs has revealed, disclosure
alone will not ensure regulatory action in instances where disclosures reveal evi-
dence of problematic behavior.Transparency, in other words, is a useful compo-
nent in providing access to industry-sponsored trials, but it is not sufficient—on
its own—to ensure adequate evaluation of clinical research, or penalization of
companies that act unlawfully. Both critics and adherents of evidence-based
medicine (EBM) must work to understand, and perhaps to change, the addi-
tional factors—such as the financial dependence of regulators on pharmaceuti-
cal companies—that have a bearing on public understandings of the safety and
efficacy of medical treatments.
EBM and the Use of “Evidence-Absent”
Guidelines: Compounding Risks to Patients?
When it first emerged, EBM appeared to represent an advantageous shift in
medicine in part because it challenged the paternalism inherent in older forms
of medicine that relied on the clinical observations of individual physicians in
order to determine the safest and most effective treatments. Because it contested
older forms of paternalism, EBM was assumed by many observers to represent a
democratizing element in health care. It was regarded as improving access to
clinical trial data and increasing the ability of patients to challenge decisions
made on the basis of eminence and seniority, rather than evidence (Isaacs and
Fitzgerald 1999; Liberati and Vineis 2004).
Despite many hopes that the r ise of EBM would democratize access to clin-
ical trial data, that hope has not,at least in the case of the SSRI controversy, been
realized. Sources of hierarchical authority have not been eradicated or mini-
mized, but have instead shifted from clinicians to the regulators overseeing the
dissemination of clinical trial information, and the manufacturers who seem
able, at present, to withhold data with impunity.
Clinical practice guidelines that NHS staff are legally exhorted to follow in
their daily practice are based on data that represents only a portion of the trials
carried out by industry and held by regulators.As the case of SSRIs reveals, the
inability of those formulating practice guidelines to fully access all available data
on a treatment has profound consequences for patient safety. In leading to the
development of guidelines that may be exposing patients to more harms than
when treatment decisions were made without reference to guidelines, EBM may
be compounding and augmenting the very problems surrounding patient safety
it was introduced to help combat.
As David Armstrong (2007) has suggested: “in an era of concern for patient
safety, EBM is proposed as part of a solution (through its claim to reduce uncer-
tainty about the effect of interventions) but remains itself a source of potent dan-
ger and increased indeterminancy” (p. 73).
214
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Co nc lu si on
Legal barriers to accessing clinical trial data affect the reliability of clinical prac-
tice guidelines. The MHRA’s failure to prosecute GSK reveals something that
has been under-examined in previous analyses of EBM: by arguing against pro-
posals for more universal access to data, regulators have effectively colluded with
pharmaceutical manufacturers in the distortion of guidelines that play an in-
creasingly important role in the delivery of medicines.
Many previous observers have suggested that EBM, through its privileging of
the evidence derived from RCTs,risks devaluing the knowledge gained through
individual clinical encounters. But the problem is not that EBM places too much
emphasis on RCT evidence, to the neglect of anecdotal evidence or self-reports
from patients. It is that advocates of EBM privilege the very data that may be the
most compromised by political and economic factors, often with the mistaken
assumption that these data are the most “evidence based.
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... An internal company memo on marketing emerged 6 years after it was written stating that GSK should "effectively manage the dissemination of these data in order to minimize any negative commercial impact" (Kondro, 2004). Uncertainty, McGoey argues, "is generative and performative" (McGoey, 2009) and strengthens the hand of authorities. Critics have long called for a safety board or what could be called a "lemons board" that would be independent of the regulator who approves drugs and is paid by the companies to do so. ...
... A study of the financial ties between principal investigators and the manufacturer of drugs being investigated in clinical trials found that when these ties were present they were independently associated with positive clinical trial results (Ahn et al., 2017). The positive biases in these trials also distort clinical practice guidelines, another tier of alleged protection against prescribing lemons (Abramson and Wright, 2007;McGoey, 2009;Nissen and Wolski, 2007;Selvin et al., 2008). ...
Article
Drawing on economic theory and institutional analysis, this paper reframes Akerlof's theory of how a market for lemons operates and argues that each of the many markets for lemons must be studied empirically to document how different stakeholders cope with the problems of information asymmetry, secrecy, and power. Such markets are a new field for sociological analysis. To illustrate, the paper characterizes pharmaceuticals as a multi-tier market of information asymmetry in which actors in each tier have substantial control over how much they disclose about hidden risks of harm. Such a market rewards the production and sale of "lemons." Current incentives and institutional practices reward developing a large number of barely therapeutically innovative drugs and ignoring their often hidden or understated harmful side effects. They reward designing and executing substandard, biased trials that mislead the FDA and regulators abroad to approve new drugs without clear evidence of their degree of harm. Approved drugs are likely to be "lemons" but promoted as "safe and effective." The result is substantial hospitalizations and deaths from adverse drug reactions. A "risk proliferation syndrome" of institutional practices maximizes sales, profits, and exposure to toxic side effects. An "inverse benefit law" of marketing operates as companies try to maximize sales. The probability of benefits decreases but the chances of lemons adverse events do not. The details presented here deepen understanding of how markets for lemons thrive on information asymmetry, secrecy, and power. Lessons can be applied to other markets.
... These critics believe the validity and veracity of peer-reviewed research is being undermined, subverting the foundation of EBM. 35,36 According to Harvard University internist John Abramson, the pharmaceutical industry has inserted itself into every aspect of medical practice, from medical education to basic research and clinical care, endangering the integrity of the American health care delivery system and subverting the trust between patient and practitioner. 24 Marcia Angell, former editor-in-chief of the New England Journal of Medicine, links the near collapse of health care in the US directly to the corrupting practices of the pharmaceutical industry. ...
... Their stories are featured in op-ed pieces and magazines: Bill W from California, denied health insurance because of a high PSA and suspected cancer, paying cash to receive a transurethral resection of the prostate (TURP) in New Delhi's Fortis Hospital for a quarter of the cost back home; Mohammed S from Kuwait, undergoing an eight-hour removal of a glioblastoma in Chennai's MIOT hospital only a few days after receiving his diagnosis at home. 35,36 Nearly 50% of patients treated in Chennai travel from outside Tamil Nadu. Chennai's hospitals go to great lengths to attract this lucrative group of patients, offering city tours, swanky hotel rooms for guests, airport pick-up and drop-off, and hours of one-on-one time with staff physicians. ...
... "How often have pain clinicians been told by payers, while withholding of payment, that 'insufficient evidence to prove efficacy' is 'sufficient evidence to prove ineffectiveness'?" (ibid). McGoey (2009) has discussed how the withholding of "marketing unfriendly" clinical trial information by multinational corporations (MNCs) and academic researchers distorts the evidence base, and could affect the reliability of clinical guidelines. Lack of effective regulatory controls has let the multinational drug industry continue doing this. ...
... A more important question arises: do those doctors who support this culture for the best of intentions -e.g., to undertake important research that would otherwise remain unfunded -have the courage to oppose practices that bring the whole of medicine into disrepute?" Until the industrial, political, and legal barriers preventing full access to clinical trial data are addressed, the ideals of evidencebased practice will remain elusive (McGoey, 2009 ...
Technical Report
Full-text available
Evidence Based Medicine & Rational Drug Usage are currently dichotomous. This article attempts to show that they are in fact complementary. Rational approach in an individual case may help one to avoid simplistic cook-book approach based only on the strength of evidence.
... Bias resulting from selective reporting can impact meta-analyses, influencing the conclusions of systematic reviews, and in turn, evidence based clinical practice guidelines. [43][44][45] One of the forgettable examples in cardiology was the removal of the Watchman LAA Closure Device in Patients With Atrial Fibrillation versus Long Term Warfarin Therapy (PREVAIL) trial 46 from the American College of Cardiology (ACC) 2013 program at the last minute because of an embargo break by the sponsor with reports of end-points being changed and attempts to not present complete data. The retraction of the Outcome of Different Ablation Strategies In Persistent and Long-Standing Persistent Atrial Fibrillation (OASIS) trial by the Journal of the American College of Cardiology also raised concerns over potential industry influence even on prominent and important scientific publications. ...
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Full-text available
The evidence-based medicine is rooted in the scientific truth. Oxford Dictionaries has released its 2016 word of the year: “Post-truth,” which they define as “relating to or denoting circumstances in which objective facts are less influential in shaping public opinion than appeals to emotion and personal belief”. In everything from climate change denial to the anti-vaccine movement, we’re seeing the consequences of a failure to engage with scientific evidence. Fake news and post-truth pronouncements are increasingly common in social media and political era and are unfortunately also progressively being applied to the medical science. We also see some evidence of post-truth signals in daily cardiology procedures and guidelines including both interventional cardiology and cardiac electrophysiology. Guideline recommendations made before the randomized-controlled trials (RCT) are published might result in a scenario that the interventions or procedures have been performed on millions of people, costing billions of dollars, leading to unnecessary use of health care resources and often, ending up being even accepted as routine procedures in certain clinical situations. “Justice delayed is justice denied” is a legal cliché meaning that if timely justice is not provided to the sufferer, it loses it importance and violates human rights. In medicine, “The RCT delayed is justice denied”, as highlighted by ORBITA (Objective Randomised Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina) trial and as is likely to happen with CABANA (Catheter Ablation versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial) in the post-truth era.
... Doubts have been raised by large number of health professionals that pharmaceutical companies have infiltrated the medical research institutions and influenced peer-review process to promote drug marketing and a few but influential medical critics believe that the validity and veracity of peer-reviewed research is being undermined, subverting the foundation of EBM. 2,9 Researchers believe that unfavorable research results are eliminated from or camouflaged in the texts of industry-influenced studies and that data often are remolded in ways that present favorable results when a more transparent analysis might reveal substantial risk for patients taking the ''hyped'' medications. 10 Internist John Abramson,11 wrote that the pharmaceutical industry has inserted itself into every aspect of medical practice from medical education to basic research and clinical care, enticing a number of respectable research physicians into endorsing questionable studies, co-opting the mechanisms of evaluation of effective treatment for widely accepted illnesses, but also it has successfully colonized the healthy population by the construction of an array of new illnesses. ...
... Over the last twenty years, social scientists studying the EBM movement have stressed that because there is no algorithmic way to practice EBM, the use of clinical expertise to interpret and integrate research evidence with patient values is always contingent on social and political factors. To take two examples, much excellent work has been conducted at the micro-level, looking at guideline development for instance, [5][6][7][8], and at the macro-level, looking at the politics of EBM [9][10][11][12][13]. ...
Article
Full-text available
Randomised trials can provide excellent evidence of treatment benefit in medicine. Over the last 50 years, they have been cemented in the regulatory requirements for the approval of new treatments. Randomised trials make up a large and seemingly high-quality proportion of the medical evidence-base. However, it has also been acknowledged that a distorted evidence-base places a severe limitation on the practice of evidence-based medicine (EBM). We describe four important ways in which the evidence from randomised trials is limited or partial: the problem of applying results, the problem of bias in the conduct of randomised trials, the problem of conducting the wrong trials and the problem of conducting the right trials the wrong way. These problems are not intrinsic to the method of randomised trials or the EBM philosophy of evidence; nevertheless, they are genuine problems that undermine the evidence that randomised trials provide for decision-making and therefore undermine EBM in practice. Finally, we discuss the social dimensions of these problems and how they highlight the indispensable role of judgement when generating and using evidence for medicine. This is the paradox of randomised trial evidence: the trials open up expert judgment to scrutiny, but this scrutiny in turn requires further expertise.
... An ample literature demonstrates significant limitations to the use of 'evidence' in the guidelines development process (Devisch & Murray, 2009;Tonelli, 2009;. For example, guidelines over-emphasize pharmaceutical treatments as these are more likely to receive funding for study and therefore be supported by 'evidence' and are often single-disease and specialtydriven in a way that makes them of little relevance and utility for many patients (McGoey, 2009;Shackelton, Marceau, Link, & McKinlay, 2009;Upshur & Tracy, 2008). ...
... However, a noninferiority trial that successfully finds the effects of the treatments to be similar has demonstrated no such thing'. 7. Noting that sample sizes in clinical phase IV studies usually are too small (about 1 million participants are needed to demonstrate statistically significant results if an adverse reaction is likely to occur in 1:100000), the American Institute of Medicine recommends that register-based, pharmaco-epidemiological studies should be used to establish the prevalence of (known) adverse effects (Institute of Medicine, 2012 (Sismondo, 2009), withholding of information about adverse effects (McGoey, 2009), and selective reporting (Chan et al., 2004). Also journalists have uncovered circumvention of established regulation; for instance, Danish journalists have identified that a considerable number of physicians did not seek approval for industry collaboration from the National Board of Health as they are required to (Vibjerg, 2013), and uncovered instances where research funds from pharmaceutical companies were not administered on a central, hospital research account as required (Pihl, 2013). ...
Article
Policies about physicians' involvement with pharmaceutical companies spawn contradictory ideas. One set of policies aims to stimulate collaboration between private companies and publicly employed researchers to spur innovation and economic growth, another addresses what is seen as the problem of physicians' conflicts of interest stemming from industry collaboration. This article explores how these contradictory policies interact with everyday practice in clinical hypertension research in Denmark. I argue that 'corporate' and 'academic' research is entangled as physicians participate in industry trials to pursue their own research. Building on document analysis, observations of contract research, and interviews with clinician researchers and industry executives, I show how the establishment of industry 'ties' can serve as a way for physicians to navigate the constraints of research infrastructures and live up to intergenerational norms that knit the medical collective together. I discuss how this entanglement shapes medical research in ways that may run counter to the aims of medical innovation policies and that conflicts of interest policies do little to address. I conclude that appreciation of the ways in which economic and moral valuations come together is necessary to understand the conditions for medical research in an intertwined public-private research environment.
... These critics believe the validity and veracity of peer-reviewed research is being undermined, subverting the foundation of EBM. 35,36 According to Harvard University internist John Abramson, the pharmaceutical industry has inserted itself into every aspect of medical practice, from medical education to basic research and clinical care, endangering the integrity of the American health care delivery system and subverting the trust between patient and practitioner. 24 Marcia Angell, former editor-in-chief of the New England Journal of Medicine, links the near collapse of health care in the US directly to the corrupting practices of the pharmaceutical industry. ...
Article
Full-text available
The CriticsEBM is not without its critics, who warn that the art of medical practice is in danger of being overwhelmed by disinterested science, on the one hand, and cost-cutting corporate bureaucrats, on the other.10,19 These concerns have grown over the years, including those of David L Sackett, one of the authors of the McMaster manifesto. Sackett questioned the direction that EBM was taking and expressed frustration over what he considered the harmful effects of expert claims.23 Other critics have characterized reliance on data from population studies and clinical trials as Galenic scholasticism, in which the skills associated with close readings of texts have replaced the actual physician–patient encounter.24 In contrast, the physician's familiarity with a patient's life history is portrayed as local knowledge that enables the clinician to tailor contextualized diagnoses, treatments, and advice that mesh with individual needs. Patient narratives serve as exemplars of what allegedly has been lost. These narratives are also literary devices that at once reveal the clinician's diagnostic and interpersonal skills, while exposing the danger of a mechanistic application of population studies. Case histories are presented as mirrors of the best of medical education in which individual cases are interrogated and, in the process, reveal why some patients fared well and others poorly when placed on similar regimens. What is at stake, these stories suggest, is nothing less than the clinical encounter itself.25,26Ghaemi reminds us that there is no such thing as “non-evidence-based” medicine, rather there are many levels of evidence, ranging from case series to doubleblind RCTs. “In my reading of EBM,” writes Ghaemi, “the basic idea is that we need to understand what kinds of evidence we use, and we need to use the best kinds we can.”27 But how robust is the evidence produced even by gold-standard RCTs? Not very, according to a recent study published in the Annals of Internal Medicine. The investigation, conducted by the Ottawa Health Research Institute, found that 15% of “best evidence” recommendations were reversed in two years; in three years, 23% were reversed; and in five and half years, 50%.28 Commenting on the study, Groopman and Hartzband noted that “Americans have witnessed these reversals firsthand as firm ‘expert’ recommendations about the benefits of estrogen replacement therapy for postmenopausal women, low-fat diets for obesity, and tight control of blood sugar were overturned.”29 Who wants their care predicated on recommendations half of which are proven wrong within five years?If clinical practice demands sensitivity, EBM, in contrast, requires specificity (reliability); each piece of data must be (as much as possible) identical to another. Thus, patients' complaints are evaluated in the context of the findings of population studies. However, according to Groopman, specificity can be misleading because patients present for treatment with combinations of conditions that do not match the evidence. For Groopman, EBM interferes with evaluating individual patient complaints because the physician is drawn toward statistical findings that seduce practitioners to cease listening even as their patients continue talking. Thus, EBM leads physicians to fail to incorporate the most important source of evidence, sensitivity to what their patients can reveal about their conditions.30 Paying attention to a patient's narrative is crucial, argue EBM critics, because patients with similar signs and symptoms, even with the same diagnosis, often require different treatment.9 Added to this is Michael Balint's observation31 that “doctors see patients because of disease. Patients see doctors because of anxiety. Therein lies the problem between the two.”
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It’s worse than you think but could be much better than you imagine. In the Introduction, we described and documented the ways in which patent-driven research and prices set at 50–100 times manufacturing costs, have corrupted the research process, the products of pharmaceutical research, medical knowledge, the way drugs are approved, and the prescribing choices physicians make. Drug companies distort each of these steps to maximize profits, usually with little benefit to patients. Risks of serious adverse reactions from new drugs are one in five.1 While patenting may work out better in other areas of industrial research like software development, funding research to find better medicines through patent-protected high prices and monopolistic submarkets has inverted or corrupted biomedical research, especially in rich countries.
Chapter
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Introduction: risk and the legalization of medicine. Not a day goes by without a major news story about healthcare. Many of these stories are about the promise of scientific discoveries and technical innovations, the hardships that arise from inequalities in access to healthcare, the courage and fortitude of patients and their families, or the consequences of medical error. Even when their ‘human interest’ lies elsewhere, a surprising number of these stories contain a dual focus on risk and rules. News stories about research often ask whether the research is too risky, what rules govern medical research, and whether these rules have been followed. When Ellen Roche, a healthy young participant in a Johns Hopkins medical research project on asthma, died in June 2001 from inhaling hexamethonium, questions were raised not only about the soundness of the science but about the ways projects and adverse events were reported and recorded (Glanz 2001). Likewise, when a young diabetic died in 2001, the spotlight fell on the consent process and whether he and his parents had been fully informed about the experimental nature of his treatment as the rules required. Once drugs or procedures receive approval, attention shifts to other risks and rules. After Jésica Santillàn received a heart and two lungs of the wrong blood type in February 2003, Duke University Hospital implemented a new rule requiring that three members of the transplant team verbally communicate the results of tests of the recipient's and donor's blood types (Altman 2003).
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Many political theorists have turned to the dramatic political events of the post-9/11 world – terrorism, war, and the erosion of civil liberties – for insight into our changing sense of the political. Yet few have examined the economic dimensions of these events or sought to learn what they might tell us about the changing nature of political community today. This article seeks to fill this gap by drawing on the work of Michel Foucault and Georgio Agamben to examine the intimate and changing relationship between the political and the economic in the contemporary world. Now more than ever, there is a particular conception of politics at stake in global efforts to govern economic relations. Global economic institutions like the IMF and World Bank are policing the definition of political community and, in doing so, extending the scope of liberal governmentality. At the same time, the character of their implementation and justification is that of the sovereign exception, as state autonomy must continually be breached through extensive conditionality in order for it to be re-established in the form of a more ‘sound’ political and economic order. This is a sovereign exception with a difference: for the norm that is being established is one that necessarily limits the scope of sovereign power in the interests of market freedom. Paradoxically, while the economy is often the exception to politics as usual, is it an exception that simultaneously enables and constrains the possibility of exercising sovereignty itself?
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Who controls indeterminacy in the doctor–patient encounter defines the nature of professional power. Evidence-based medicine (EBM) is one such control strategy claiming to reduce uncertainty by identifying effective (and efficient) interventions and by removing ineffective treatments from clinical practice. EBM, however, as a means of keeping some autonomy for a profession beset by increasing government control, has had to compete with other professionalizing strategies within medicine. And, despite its promise, EBM is shown not to have reduced indeterminacy but to have shifted the problem into a wider policy arena that involves interpreting evidence. Moreover, in an era of concern for patient safety, EBM is proposed as part of a solution (through its claim to reduce uncertainty about the effect of interventions) but remains itself a potent source of danger and increased indeterminacy.
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This paper serves as the foreward to a collection of articles published in Law and Contemporary Problems (October 2006) entitled Sequestered Science: The Consequences of Undisclosed Knowledge. Authors explore the pros and cons of keeping scientific evidence secret and describe institutional arrangements authorizing or prohibiting secrecy, such as court-sanctioned settlements, confidentiality agreements, and clinical trial registries. Legislation modeled on the Sarbanes-Oxley Act is proposed as a means to improve accountability in producing and submitting scientific data used in public health and environmental protection programs.
Book
'Transparency' is widely canvassed as a key to better governance, increasing trust in public-office holders. But it is more often preached than practised, more often referred to than defined, and more often advocated than critically analysed. This book exposes this doctrine to critical scrutiny from a range of disciplinary perspectives, including political science, philosophy, and economics. It traces the history of transparency as a doctrine of good governance and social organization, and identifies its different forms; assesses the benefits and drawbacks of measures to enhance various forms of transparency; and examines how institutions respond to measures intended to increase transparency, and with what consequences. Transparency is shown not to be a new doctrine. It can come into conflict with other doctrines of good governance, and there are some important exceptions to Jeremy Bentham's famous dictum that 'the more closely we are watched, the better we behave'. Instead of heralding a new culture of openness in government, measures to improve transparency tend to lead to tighter and more centralized management of information.
Article
This essay originally was presented orally at the University of Cincinnati College of Law's Sixteenth Annual Corporate Law Symposium. The essay describes corporate agency and agency-related relationships as implicated in the "Enron affair" and explores ways in which the Sarbanes-Oxley Act of 2002 fails or attempts to address the alleged malfunctions in these relationships. The essay concludes that the reforms enacted in Sarbanes-Oxley provide little assistance in resolving agency and agency-related problems associated with Enron's public misstatements and omissions. Ultimately, the essay exhorts scholars and practicing lawyers to work together to resolve these problems through (among other things) additional research into cognitive and behavioral science and direct client assistance both in the decision making process and in the search for and selection of corporate directors and officers.
Article
‘Organizational encounters with risk range from errors and anomalies to outright disasters. This collection of essays addresses the varied ways in which modern organizations understand, process and deal with risk. Contributions by leading experts on risk management illustrate the complex organizational and social dimension of risk management, reminding the readers that effective handling involves much more than the application of technique.
Article
This article examines how scientists and regulators distribute the benefit of the doubt about drug safety under conditions of scientific uncertainty. The focus of the empirical research is the regulatory controversy over the hepatorenal toxicity of benoxaprofen in the United Kingdom and the United States. By scrutinizing the technical coherence of the arguments put forward by industrial and government scientists, it is concluded that these scientists are willing to award the commercial interests of the pharmaceutical industry an enormous benefit of the sccentific doubt, which is not consistent with the best interests of patients. Interpretative flexibility, the burden of proof falling on regulators and their trust in, and dependence on, industrial scientists facilitates that distribution of the benefit of the scientific doubt. However, regulatory authorities' need for viability and the rationality common to opposing scientific views suggest that it is possible, in principle, to alter this dominant trend. To achieve adequate patient protection, drug regulation in the United Kingdom and the United States requires extensive reform. Some preliminary policy changes are sketched.