Guest guest Posted September 8, 2004 Report Share Posted September 8, 2004 > SSRI-Research > Tue, 7 Sep 2004 22:39:54 -0400 > [sSRI-Research] Posting Clinical Study > Summaries and the Marketing of Unsafe Drugs - By > Bryan Johnston > > Drug Safety and the Hawthorne Effect > Posting Clinical Study Summaries and the Marketing > of Unsafe Drugs > By Bryan Johnston > > In the recent settlement of GlaxoSmithKline > (GSK) with the Attorney General of the State of New > York, Eliot Spitzer sought to provide the public > with protection from undisclosed adverse drug events > caused by FDA approved medications. However, by not > insuring that the raw data from all clinical study > reports (CSR) are available for public review prior > to the active marketing of any medication, the > public remains at risk. > The consent order of August 26, 2004, was > advantageous for GSK, and the pharmaceutical > industry as a whole, for it did not address the > concerns of; 1) the bias inherent in the published > evaluations of clinical studies performed by the > pharmaceutical industry, nor 2) the industry's > ability to influence the prescription habits of > physicians as a group prior to the public posting of > CSR summaries and thereafter. > The Timing of New Black Box Warnings (1) > exemplifies this controversy regarding the safety > and efficacy of prescription drugs. One significant > result is an increase in litigation and Physician > insurance generated by the harm imposed upon the > general public. > One of the recognized causes of this public > health risk is the pharmaceutical industry's > practice of withholding negative CRS from > publishing. Marketing has become the preferred > strategy for CRS publishing, hindering the > dissemination of scientifically valid information. > While the industry's move towards publishing > summaries of all CSRs is a step toward full > scientific disclosure, it will not provide > physicians with the information necessary to > objectively determine a new drugs safety and > efficacy. > The Placebo Effect has been long recognized for > its potential to generated biased results. Clinical > trial test subjects also have a recognized > sensitivity for Experimenter expectations. The > Randomized Controlled Double-Blind Testing Trial > (RCT) was created to control for these recognized > forms of experimental bias. However, the Evaluators > of clinical trials are being influenced by the > Hawthorn Effect, as applied by the drug companies, > causing a new but uncontrolled form of bias. > The Hawthorn Effect has been well established > in the field of Industrial Psychology since Western > Electric's Organizational Studies, led by Elton > Mayo, discovered it in the 1930's (2). It has its > roots in the Heisenberg's Uncertainty Principle in > quantum physics that was being investigated at about > the same time, stating that one cannot measure an > outcome without affecting the outcome. Mayo's > discoveries of the psycho/social influences that > effect motivation in the work place forever > revolutionized business, creating the School of > Human Resources at Harvard University. > The Hawthorne Effect states that anyone can be > motivated, by the proper implementation of > psycho/social influences, to naturally want to > achieve that which will satisfy those who observe > and evaluate them. The most important influences > that affect motivation are the satisfaction of a > person's need for security, recognition and a sense > of belonging. > Drug companies apply the Hawthorne Effect by > funding the RCT Evaluators, promoting their sense of > importance and creating an aura of inclusion on a > team. They then express an explicit desire for > positive results and closely observe and evaluate > the testing process. Drug companies know that under > these conditions, their observation and evaluation > naturally affects the performance of the Evaluators. > Scientific evaluation, which values safety and > efficacy over profits, is being compromised. > Research is showing that RCTs conducted by > for-profit companies approve 51% of the drugs they > test, while those RCTs conducted by independent > non-profit companies only approve 16% of the drugs > they test, casting doubt on the validity of results > published by for-profit companies (3). The > scientific integrity of RCT evaluation cannot be > properly maintained when profit oriented drug > companies provide oversight and control the release > of the raw data. > This business driven research bias was not > foreseen 40 - 50 years ago when RCT protocols were > developed and conducted by medically driven > researchers. In medically driven research, the > Hawthorne Effect would act to uphold the values of > medicine and the integrity of science. > Information being released through the court > system and by investigative journalists reveal that > the Drug Company/ RCT Evaluator relationship can > lead to publishing a more favorable outcome for new > drugs than the raw data supports. > One such example of this bias is that of the > evaluation for Eli Lilly's Prozac. Evaluators for > Prozac did not publish the administration to test > subjects of benzodiazepines to control the > akinesia/agitation that was developing during the > first two weeks of the RCTs. Lilly's CEO in > Germany, Claude Bouchy, sent a memo in 1990 to Lilly > executives in the US, demonstrating his dismay of > Lilly evaluators, at the bequest of the Drug > Epidemiology Unit, hiding attempted and successful > suicides in the published results by reclassifying > this information as 'agitation', 'aggression' or > 'depression.'(4, p.86). The withdrawal of Lilly's > drug Oraflex from the market in 1982 exemplifies the > ongoing nature of this industry-induced bias. > Manipulation of the raw data occurred with > GSK's drug Paxil. An investigative reporter > discovered that some suicidal reactions occurring > during clinical trials had been classified as > 'emotional liability'. This discovery precipitated > GSK's June 2003 warning regarding suicidal reactions > in children and adolescents (5). > Summaries of CSRs that do not provide access to > the raw data will not reveal enough information to > safely protect doctors and patients from foreseeable > adverse drug reactions. > The pharmaceutical industry's marketing > departments have long recognized Mayo's discovery of > motivational influences and the effect they can have > upon individuals and groups. They have become adept > at understanding and manipulating the behavior of > groups. > Another of Mayo's findings was the realization > that when ever a group starts to act in a coherent > and productive fashion, it becomes impervious to > change, more so than an individual would. A group > resists examining their behavior when isolated > events occur that contradict the group's beliefs. > It takes an enormous event, or an intensive > sustained effort, to alter group behavior. The > pharmaceutical industry understands this. > Once drug companies convince physicians as a > group, of a drug's ability, that belief is not > easily changed. Utilizing Mayo's finding, drug > companies contract with large public relations > firms. These firms insure the immediate and massive > dissemination of medical representations supportive > of drug company interests when adverse drug related > events become public. With the use of ghost > writing, drug companies strive to promote their > interests in professional publications. The end > result is credible research that contradicts > established drug company representations cannot have > the impact necessary to generate a balanced > perspective. The pharmaceutical industry relies upon > this phenomenon of group cohesion and their ability > to manipulate it to maintain physician prescription > habits. They excel at marketing their products. > The busy physician cannot afford the time to > evaluate all the information necessary, prior to > deciding upon prescription, when it is publically > posted in mass after intensive marketing. The > publishing of all CSR summaries will help to bring > scientific integrity back to the prescription drug > market only if all the results become available > before the pharmaceutical industry is allowed to > market their drugs. GSK's voluntary publication of > summaries from all CSRs within 10 months of approval > for marketing allows ample time to actively motivate > physicians, as a group, to adopt a prescription > practice that includes their new drug. > This necessity for timely public disclosure > comes from the behavior of the drug companies > themselves, who can make false and misleading > representations to physicians about their drugs. > One example is Warner-Lambert (W-L) and it's drug > Neurontin. W-L recently paid a $430 million > settlement for having its top executives encourage > its sales reps to fabricate positive assurances to > Physicians that Neurontin had treatment capabilities > that it clearly did not, while down playing known > risks. In accord with the Hawthorne Effect, all > involved, from the sales reps through management, > naturally sought to produce only that which their > superiors wanted to see, disregarding established > safety procedures, creating a public health risk. > The pharmaceutical industry realizes that > providing public summaries of all CTRs will not > reveal any bias in the evaluation of the raw data, > or interfere with their ability to influence > prescription practices by controlling the > dissemination of information. While publishing CSR > summaries will make it more difficult to withhold > negative results from public disclosure, all major > corporations accept that the litigation, which > develops regarding their products, is often a lesser > expense than further R & D. The FDA is unable to > adequately police the enormous volume of industry > representations. Drug companies realize that the > FDA's enforcement is generally limited to > cease-and-desist letters. W-L's Neurontin is > currently generating $2.7 billion in annual sales. > Only an informed medical opinion concerning a > drug's safety and efficacy, rendered prior to > marketing, can avoid the emergence of adverse drug > related events that pharmaceutical industry would > prefer not be made public. > To control for the Hawthorne Effect this author > supports having the results of all clinical trials, > from Phase III on, be published as they occur. This > would allow medicine to track a drugs progress well > in advance of approval, allowing a general consensus > of safety and efficacy to develop based upon > accepted medical standards. Physicians need to be > able to access the raw data to verify the > conclusions of the original evaluation as a > non-biased third party. > The creation of an independent, non-profit, > international agency to conduct all RCTs would also > insure scientific integrity. Such an agency could > use its expertise to adequately test all new > compounds using improved protocols that would be > sensitive to all experimenter bias and to a myriad > of adverse effects, as well as for additional > effects that could generate an unexpected marketing > ability. > > References > > 1 - Lasser KE, Allen PD, Woolhandler SJ, Himmelstein > DU, Wolfe SM, Bor DH. > Timing of new black box warnings and > withdrawals for prescription medications. > JAMA. 2002;287(17):2215-20 > 2 - Manufacturing Knowledge : A History of the > Hawthorne Experiments > Richard Gillespie > Cambridge University Press August 30, 1991 > 3 - Bodil Als-Nielsen, MD; Wendong Chen, MD; > Christian Gluud, MD, DMSc; Lise L. > Kjaergard, MD > Association of Funding and Conclusions in > Randomized Drug Trials > A Reflection of Treatment Effect or Adverse > Events? > JAMA. 2003;290:921-928 > 4 - The Anti-depressant Fact Book > Peter R. Breggin, MD > Perseus Publishing, Cambridge Massachusetts > 2001 > 5 - How Pharmaceutical Companies Mold our > Perceptions of Mental Illness > David Healy, M.D., F.R.C. Psych > UCLA Neuroscience Lectures Oct. 28, 2003 > http://www.mentalhealth.ucla.edu/opce/gr.html Quote Link to comment Share on other sites More sharing options...
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