I must be slipping.
Well, not really. It doesn't bother me that blog bud and fellow skeptical physician PalMD beat me to an important publication that came out a couple of days ago in the Annals of Internal Medicine. I'm a surgeon and a translational/basic scientist; so Annals is not usually one of the journals I read regularly. I usually read individual studies as I find out about them referenced elsewhere, usually Eureka Alert! or when an Annals study sufficiently interesting to motivate me to surf on over to the website and download the article. Be that as it may, this article is highly relevant to the overall themes of this blog because it shows yet another manner in which science-based medicine can be undermined. This time around, though, it's not so-called "complementary and alternative medicine." It's not woo-meisters. It's not even the infiltration of pseudoscience into academic medical centers.
No, this time around it's big pharma doing the sorts of things that produce such marked distrust, even among advocates of science-based medicine.
The problem highlighted by this article is a phenomenon known as a "seeding" trial, specifically a seeding trial carried out by Merck for Vioxx. Seeding trials are a special breed of trial that is carried out either shortly after the Food and Drug Administration (FDA) approval of a new drug or while a drug is being considered for approval by the FDA. Normally, one would think that a trial shortly after FDA approval would be for the purposes of post-approval surveillance of a drug for safety and efficacy. After all, the phase III clinical trials that are used pre-approval to establish the value of a new drug are not and cannot cover nearly as many patients as will be taking the drug after it's approved. There are sometimes rare effects that show up only after a drug has been administered to hundreds of thousands or millions of people. Given that it's utterly impractical to test a drug on that many people before its approval, and post-approval monitoring is essential.
That's not what we're talking about here.
No, what we're talking about is a study that appears to be a valid clinical trial but is designed for a different, unspoken and unrevealed purpose. This type of trial, known as a seeding trial, involves coming up with a hypothesis to be investigated that isn't really that important and then designing a study in such a way as to get the new drug into the hands of as many primary care physicians as possible. Community primary care doctors rarely participate in clinical trials. The reason for this is because they are very busy, and signing up patients for clinical trials is very time-intensive. It takes hours to check patient eligibility, explain the trial, obtain informed consent, register a patient with the clinical trial office doing the trial, and doing the necessary documentation. Most community physicians have not been trained in clinical research and do not have the skill set to deal with clinical trial issues themselves. Moreover, many community primary care practitioners operate on razor-thin margins; spending that much time signing up patients can seriously jeopardize the financial health of their practice.
Enter the drug company and the seeding trial. In such trials, many, many physicians are signed up as investigators, so that each only has to sign up a few patients, and the drug company pays them for each patient and provides all the support necessary for monitoring and paperwork. Meanwhile the reward for physicians participating is the prestige of being an investigator for a clinical trial, coupled with in essence no penalty because the drug company more than reimburses for the time spent, which isn't all that much given that each physician only has to sign up a few patients. In reality, however, the design of the trial is very inefficient. For a real scientific question being tested in a clinical trial, it would be far more efficient to concentrate the patient accrual in a few large academic centers that could find patients much more quickly and already have the infrastructure to do clinical trials. But for seeding trials the scientific question is almost besides the point, an afterthought. The real, unstated purpose of such trials is to expose as many doctors as possible to using the drug and thereby make them comfortable using it. The real purpose of seeding studies is to make these physicians advocates for the new drug. The real purpose of seeding trials is marketing, not science.
The Annals article drives this home quite effectively with a case study of the ADVANTAGE (Assessment of Differences between Vioxx and Naproxen To Ascertain Gastrointestinal Tolerability and Effectiveness) clinical trial run by Merck. The stated purpose of this trial, which involved 5,557 patients at 600 different sites, was to compare gastrointestinal side effects and tolerability of Merck's new drug Vioxx with those of an established drug (Naproxen) whose results were published in 2003 in--of all journals--the Annals of Internal Medicine. Not surprisingly, the results of the ADVANTAGE trial showed that Vioxx was superior to Naproxen when it came to gastrointestinal side effects. However, there was a huge problem.
As Merck internal documents clearly show, the ADVANTAGE trial was primarily a marketing tool. Think of it as a direct-to-physician sales pitch, as demonstrated quite clearly by this document, which I urge you to take the time to read. Here's a key passage from this document originating from Merck's marketing department:
The ADVANTAGE (Assessment of Differences between Vioxx and Naproxen To Ascertain Gastrointestinal Tolerability and Effectiveness) trial is the largest ever initiated prior to the launch of a Merck product. The objectives were to provide a product trial among a key physician group to accelerate uptake of VIOXX as the second entrant in a highly competitive new class and gather data important to this customer group. The trial was designed and executed in the spirit of the Merck marketing principles, as described below.
First, the trial was targeted to a select group of critical customers. The clinical trial program for VIOXX focused primarily on specialists. While they would be critical to early uptake and advocacy for VIOXX, the large majority of prescriptions in the A&A market (~60%) come from primary care physicians. The ADVANTAGE trial utilized this important group of prescribers as investigators. In addition to gaining experience with VIOXX, many of these physicians gained a highly coveted introduction to clinical research.
In other words, the introduction to clinical research was secondary, and the actual scientific question to be answered was dead last in Merck's considerations. Indeed, the most important part of the memo appears to be the part where it is emphasized is the careful tracking of marketing-related results; i.e., rates of Vioxx prescriptions written by study physicians. There's also this slide from a Merck presentation, which defined the role of the marketing department in the design and execution of ADVANTAGE thusly:
- Design protocol and oversee execution of trial
- Select investigator sites
- Run investigator meetings
- Choose and manage CRO (clinical research organization)
- Perform data analyses
- Prepare publications
Worse, even though the first author of the main publication resulting from ADVANTAGE was Dr. Jeffrey R. Lisse, an academic physician not employed by Merck, as reported in the New York Times, he did not have a role in data collection or analysis and was quoted thusly:
"Merck designed the trial, paid for the trial, ran the trial," Dr. Lisse said. "Merck came to me after the study was completed and said, 'We want your help to work on the paper.' The initial paper was written at Merck, and then it was sent to me for editing."
Clearly, Dr. Lisse was seriously compromised ethically by Merck, as well. He should have either refused to help or demanded a much greater role in the analysis of the data. To do otherwise is to let oneself become in essence a front man for a big pharma-produced marketing document.
To boil it all down, here's my perspective on why seeding trials such as this are inherently unethical, regardless of whether the clinical scientific question under study is worthy or the design of the trial can produce an answer. It all comes down to one issue: Deception. There is no way to carry out such a trial without deceiving everyone involved below the level of study designers. First, the physicians recruited as investigators can't know that they are in fact the real study subjects, given that the real purpose of a seeding study is to determine whether giving them exposure to using the drug will change their prescribing habits and make them advocates. the renumeration and stroking by the drug company also compromise their objectivity to an unacceptable degree. (No clinical investigator can ever be truly 100% objective, because all clinical investigators have some degree of an emotional investment in the outcome of the studies they design and perform. That's why we have so many safeguards on clinical trials.) Second, the patients recruited as human subjects can't know one of the major questions of the study, again whether physicians' prescribing habits can be changed. This alone means that truly informed consent is impossible. Finally, the very committee charged with protecting the interests of human subjects in clinical trials, the Institutional Review Board (IRB), must also be kept in the dark regarding the marketing purpose of the study. The reason is obvious. No IRB would approve a human subjects study whose primary purpose is clearly marketing more than an important scientific question.
As an accompanying editorial by Harold C. Sox, MD, Editor of Annals of Internal Medicine, and Drummond Rennie, MD, puts it:
No one told Annals the true purpose of ADVANTAGE. We learned about it when we received a letter to the editor from Dr. David Egilman, who was a consultant to the plaintiffs' attorneys in the civil suits against Merck (7). He had access to publicly accessible trial documents, which included Merck employees' e-mail messages that disclosed the true intent of the ADVANTAGE trial. These messages are the meat of the article about seeding trials published in this issue by Hill and colleagues (8). To our knowledge, this article is the first to provide documentary evidence that proves the existence of seeding trials. Other than an excerpt from a single industry document cited in an article by Kessler and colleagues (9), we have not had "smoking gun" evidence, in which the perpetrators are on public record about why they conducted a trial like ADVANTAGE. The article provides clear evidence that the intent of ADVANTAGE was to increase prescriptions of Vioxx (the study outcome of greatest interest to Merck seems to have been Vioxx prescribing rates). However, despite the large body of documents searched by the authors, they discovered few details about exactly how Merck's marketing division carried out ADVANTAGE.
The documents do tell us that deception is the key to a successful seeding trial. That information--once it becomes general knowledge--could be the fatal blow for seeding trials. Institutional review boards, whose purpose is to protect humans who participate in research, would probably not likely approve an action that places patients in harms' way in order to influence physicians' prescribing habits. If they knew, few established clinical researchers would participate as coinvestigators. Few physicians would knowingly enroll their patients in a study that placed them at risk in order to provide a company with a marketing advantage, and few patients would agree to participate. Seeding trials can occur only because the company does not disclose their true purpose to anyone who could say "no."
The problem for clinical investigators and busy clinicians, as well as IRBs, is identifying a seeding trial. It's not as easy as it may seem. For example, ten years ago, when the ADVANTAGE trial was being planned and submitted to IRBs, the scientific question to be answered by the trial was not an unreasonable one. Moreover, there are perfectly valid reasons for doing a trial using many community practitioners rather than academic centers, inefficiencies of this approach notwithstanding. The key advantage is to obtain "real world" data about side effects and efficacy when a drug is prescribed "in the real world," so to speak. Academic medical centers that do a lot of clinical trials are places with a rarified atmosphere and resources not available to most community physicians. It is often of interest to know how a drug will work "in the wild." In addition, some inducement is necessary to get community physicians on board, given that the constraints on their time and finances usually make being an investigator in a clinical trial too onerous. Indeed, that the ADVANTAGE trial was a seeding trial did not become apparent until long after it was published, and an article in the New York Times suggested that its purpose was more for marketing than for science.
One characteristic that is common in a seed trial is that it is redundant. In other words, it is asking a question that has already been answered. Certainly, this was the case with the ADVANTAGE trial, as the incidence of gastrointestinal side effects had already been assessed and shown to be lower than those due to Naproxen in an earlier trial known as the Vigor Trial.
Given the huge expenses involved in developing new medications and bringing them to market, I am under no illusions that drug development will ever be done to a significant degree by any other entities than for-profit companies. Indeed, the profit motive, when harnessed and regulated, is a powerful incentive, although it can also motivate trials like the ADVANTAGE trial. Nor am I under any illusion that the authors of this study are as pure as the driven snow. All of them were compensated for participation in litigation against Merck at the request of plaintiffs, and their access to internal Merck documents came through the discovery process during litigation against Merck. They are all hired guns for the plaintiffs suing Merck. No doubt this article will feature prominently in the many lawsuits against Merck and represents just one side of the story. Even so, that side of the story is so compelling that it is hard to imagine a defense that would excuse the clear marketing purpose of the ADVANTAGE study. Although it is (barely) conceivable that that mitigating documents might come to light during Merck's defenses against Vioxx lawsuits internal documents mostly speak for themselves. They make it very clear that the ADVANTAGE trial was a seeding trial using a previously answered scientific question as the basis of a redundant clinical trial whose real main purpose was to "seed" experiences prescribing Vioxx to several hundred primary care physicans.
For science-based medicine to be accepted and trusted by the public, the public must be sure that the clinical trials designed to test the safety and efficacy of new drugs conform to the highest standards of science. More importantly, they must know that these trials are as free from bias and hidden agendas as is humanly possible to achieve. Also, a personal standpoint, I detest Merck's actions because it will make it that much more difficult for honest clinical investigators like myself to win patients' trust and persuade them to agree to participate in clinical trials, particularly trials in which a pharmaceutical company is involved but the distrust will spill over to all clinical trials, even NIH-funded trials. The reason seeding trials like ADVANTAGE are so pernicious is because they undermine faith in science-based medicine and contribute to the distrust of "conventional" medicine by corrupting academic physicians, community physicians induced to take part in them, and even clinical science itself.
REFERENCES:
1. Hill, K.P., Ross, J.S., Egilman, D.S., Krumholz, H.M. (2008). The ADVANTAGE Seeding Trial: A Review of Internal Documents. Annals of Internal Medicine, 149(4), 251-258.
2. Sox, H.C., Rennie, D. (2008). Seeding Trials: Just Say "No". Annals of Internal Medicine, 149(4), 279-280.
Wow! Great article, Orac. It is truly frightening how much influence Pharma has over the medical community. Money seems to trump science way too often within the Pharma industry. Thanks for the article.
Apologies if the answer is buried in there somewhere, I've only had an opportunity to skim read it so far, but I wonder if there an alternative possibility?
For example, is it at all possible that ADVANTAGE (ADVANTATGE, surely?) was conceived as a meaningful scientific trial, and the marketing division said "hey, lets kill two birds with one stone and use this for marketing as well!" It's still a co-opting of the trial which has made it less effective, which is a worry, but might not be quite as grim as made out.
Also, I'm curious about who the memo's are to and from, and at which stage in the conception of the trial they were made. This is crucially important, as the impression is given that it is the marketing department who has dreamt up the seeding trial; wheras if it were a discussion of the marketing implications of a clinical trial which has already been planned by scientists, a discussion conducted between solely marketing people on the understanding that the scientists would could prioritise the science in their own memos, you can quite easily understand why the science takes a back seat.
Is that possibility addressed by the paper? (Genuine question, I'm curious, and don't have the time or patience to trawl through it in detail).
Either way, it's still pretty dangerous for clinical trials to be compromised for marketing purposes.
I wonder if this trial was literally illegal. As you point out, the Merck documents seem to make clear that the real subjects of the trial were not the patients but the investigators. Yet they did not give informed consent (since they weren't informed).
What if some university sociology professor wanted to study physicians' prescribing habits in a way that required direct interaction and data collection from the physician-subjects? Wouldn't he be legally required to obtain informed consent from those physicians?
Anybody know?
"Money seems to trump science way too often within the Pharma industry."
The company (usually publicly traded) is run by business folk...their focus is $. The efforts of the scientific staff are for the treatment of diseases and betterment of mankind. It would be incorrect to believe that pharma (or as you like to identify it as pHARMa) is and will only be subject to the agenda of those business elements is off-base, just as the concept of government is evil because of some politicians indiscretions.
The scientific and medical community is aware of how business is conducted and is committed to keeping it in check. It would be appropriate to not damn the whole institution and to recognize we (including all ove our families) are on the same team.
@ Qetzal: Yeah, these `trials` are legal. Skivvy, buy legal. Or has been in the past; maybe someone could make a better claim with this.
Yes. This is a parallel to your previous comment in: Searing stupidity about "complementary and alternative medicine" (CAM) in Slate.
Similarly, 'respectable' research conducted with integrity takes on the taint of guilt by assocation. I thought that Dr Scolnick's (Merck's head of research division) e-mail from 4 April 2001 was telling in this regard.
When these sort of studies are published in top-tier high-impact journals it undermines the status of the peer-review system even further.
This is what happens when medicine is practiced as an economic proposition. Marketing people don't understand the nature of science or research, nor should they be expected to. So when they are intercalated into the medical enterprise, they do what they do - sell the product - and we get diluted science. And given any opening, marketing will intercalate. There should be a wall of separation between medical research and marketing - a really thick wall, like the Great Wall of China. But, we've left the gates open for the barbarians and they're tougher than bedbugs to get out.
RJ,
I was merely agreeing with Orac. These types of scandals, including Vioxx, Paxil, and numerous others are key factors in why the public is losing faith in the Pharmaceutical and Medical industries (Many people loop them into the same industry). The public perceives that the Pharma industry is more concerned about money than it is about the safety and health of its consumers. Again, as Orac put it, this is about Public Perception and how it is being damaged by these scandals.
Aren't all studies done by a for-profit company designed to help sell the product? Pre-market approval studies are designed to win approval to market a device or drug.
Are you suggesting even in PMA studies that certain end points should not be studied because the whole reason for that end point is so that the marketing department can claim a selling point?
Of course deceiving an IRB about the nature of the study is wrong in many respects. And the fact that Merck's marketing department(as opposed to the clinical study department) designed, executed and analyzed the data from (biostatisticians in the marketing dept?) the study in every respect is chilling (abhorrent?).
But it seems that your argument is more than just "deception of IRB is bad". You argue that all studies should be done to "the highest standards of science" which implies that any endpoint that is designed to help sell the product is somehow lacking. And that doesn't seem right.
Are there endpoints that shouldn't be studied?
Scandal in Vienna
Nature: "... something, it seems, is rotten in the state of Austria"
http://www.transgallaxys.com/~kanzlerzwo/showtopic.php?threadid=4105
(Orac, in case it does not fit here, please move it to a better place.
Thank you,
ama)
Unfortunately, seeding trials are not new and not rare. As far as I can tell, they are not illegal. They certainly are effective for the drug companies. My own view is that they are only slightly more effective than direct-to-physician marketing efforts that use free samples initially followed by discount coupons. In psychiatry and neurology, some drug companies provide convenient starter packs with gradually increasing doses of mood stabilizers or anticonvulsants. Companies that offer such packs do much better than those that do not, because writing and filling a starter prescription is such a pain.
The point I'm making is that seeder trials seem no worse than other efforts to market drugs, and there's a small chance that the trial might generate useful information.
Is writing this going to compromise to your shill money?
"Seeding Trial" in this case being euphemism for "marketing".
wonderful. As if the science-based medicine camp didn't have enough problems. Now, I'm no doctor, but I see some serious symptoms of Foot-in-Mouth disease over at Merck.
Dr. Orac, this is probably going to make you feel like Barack Obama when he was endorsed by Ahmadinejad, but that was a nice piece.
I was seeing someone who worked for one of those medical ghostwriting firms. The stuff they got up to was definitely pushing the bounds of ethical acceptability. Really quite shocking. Multiple, clinically irrelevant, endpoints and outcome measures, the lot.
I got the impression that smaller journals were even more vulnerable to being swayed. 'Friendly' editorial boards and the promise of an order of 20 000 reprints (which should help keep a struggling journal afloat) would seem to me to rather expedite publication...certainly it could make a paper more likely to be sent for review.
For those who haven't read it, I found Trisha Greenhalgh's book 'How to read a paper' is really useful when digesting trials. It's available online:
http://www.bmj.com/collections/read.dtl
It also has a list of questions to ask drug reps (http://www.bmj.com/cgi/content/full/315/7106/480)
Orac. You surprised me with this one. Just when I thought you were totally brain dead, you present a piece that clearly shows why we all, and individually must keep our guard up.
But be very careful here Orac, as you yourself could become disenchanted with current methods of what is at times presented as "proper scientific investigation". Good lord, boy, be careful, as you are stepping perilously close to becoming a, dare I say it, a real skeptic, which could eventually even lead you to becoming a damned "dissident"!
Your investigation of seed trials should also help to open your eyes as to why so many are indeed becoming anti-establishment, be it vaccinations or be it the issue of hiv/aids.
Just think to your own self how the following situation is ripe for corruption:
In HIV land, we have the AIDS Clinical Trials Group, or ACTG, which is run at the top from the good ole boys at the NIH's NIAIDS department. They have singlehandedly run ALL aids drug research, and have had the same guys running the show for 25 years in the various ACTG drug trial centers. The former Director of Clinical Research at NIAIDS, a Dr. William Paul, was even recently found to have taken $930,000 in stock and cash from drug companies in just a 2 year period, on top of his taxpayer paid earnings at the NIH.
Now, here in San Diego, where I am living, our ACTG center is known as the AVRC or AntiViral Research Center. It is overlorded by a guy named Dr. Douglas Richman (just love that last name), who was also on the original Burroughs Wellcome team in the very first AZT trial in 1987 that lasted for just 4 months before AZT was approved for all HIV positives. He also runs the entire HIV/AIDS unit for the Veterans Administration.
I myself went to the front office intake director of the the AntiViral Research Center (AVRC) and I got her into her office for a peaceful one on one, and directly and pointedly asked her 3 questions that blew her away. Her answers blew me away.
I asked:
1) Does the AVRC get paid by the pharmaceutical companies for the drug trials on a "per patient" "per study" "per drug basis? The reason I asked is because many of the volunteers are on more than one drug, and enrolled in more than one study.
She looked at me aghast and told me "Yes, the AVRC gets paid by the drug companies on a per patient, per drug, and per study basis".
2) I asked how much the average payment from the drug companies was, per patient, per drug, and per study.
She again looked a bit aghast, and told me "$3000 to $10,000 and up".
(Who knows what "and up" means.)
3) I asked: "Does the AVRC inform the volunteers of the conflict of interest?"
She told me "No, we do not inform them".
Is that mind boggling to you, Orac? Because it is to me, but it is standard procedure in the ACTG aids drug trials.
Now let me tell you what else we have going on here in San Diego hiv land, Orac.
The AVRC convinced the local county government to send all HIV positives directly to them. The county refers to AVRC as the "First Line Of Defence". Everyone testing hiv poz in the county is referred to the AVRC.
The AVRC is even staffing and running the county governments mobile hiv testing units. The AVRC advertises in local gay and black media to come to the AVRC to get tested for HIV.
Those being diagnosed as HIV poz by the AVRC are then encouraged by the AVRC employees to join the AVRC drug trials, where they are told they will be given free aids drugs during the trials, and will assist in the paperwork to get the drugs covered by ADAP, and other taxpayer paid hiv drug programs.
No doubt this also gets the diagnosed into the habit of lifelong regimens selected by the drug trials groups, and also gets plenty of pharma-ducats into the trials groups for the "studies".
So, not only is the AVRC and the rest of the NIH run ACTG aids drug trials groups giving the majority of the hiv diagnoses, they are also running all of the aids drug research, they are also getting paid by the NIH, the county, and the drug companies, they are also doling out the majority of the drug prescriptions.
The directors of the actg groups are all paid "consultants" for the represented drug companies. And those running the ACTG groups, such as Dr. Douglas RICH-man are in a PRIME POSITION to know EXACTLY what drug companies stock will be the next to go up as a result of what drug is expected to be approved for use.
When the nevirapine hiv012 studies were questioned, due to whistleblower Dr. Jonathan Fishbein, Dr. RICHman was scheduled to be on the investigating panel, but as he was paid by both the NIH and the drug manufacturer, they decided to replace him at the last minute with someone who only got money from the NIH.
Let me ask you Dr. Orac. This has gone on across the US for many years. It is standard practice in HIV land. Most independent doctors who treat those diagnosed as HIV are ALSO paid consultants for drug companies.
Orac, Does all this AIDS CLINICAL TRIALS GROUP running the county hiv drug programs, as well as diagnosing nearly all the hiv positives, as well as running all of the pharma paid and nih paid hiv drug research, as well as running nearly all of the hiv drug prescribing sound Kosher to you? This group has been running nearly the entire show worldwide from A to Z for 25 years.
Even Bob Gallo's group runs the ACTG center in Baltimore. And by the way, Gallo's group has more people testing as hiv positive then anywhere else in the country.
Perhaps this will also help you to understand why so many are so very skeptical of all of hiv/aidsdom. The entirety of the show has been run by NIAIDS, headed by Tony Fauci since 1984, wherein there has been no change of management, no cure, no lives saved, no vaccine, a majority of deaths still due to the AIDS drugs, nothing but conflicting studies, while billions more are thrown at it, and nothing in hiv land has changed in 25 long years.
For the benefit of any lurkers reading Michael's rant:
It's a very standard practice in clinical trials to compensate the physician &/or the clinical trial center a set fee for each patient they study in the trial. That pays for the time the physician and his nurse(s) spend on each subject (plus facilities & overhead).
Subjects have to be interviewed to ensure they qualify, verbally informed of the study, given physicals, have their histories and meds reviewed, given the study drug, observed, have samples drawn, have their charts reviewed, etc. The amount of work per patient is quite substantial, and it's certainly reasonable to compensate the MD and the center accordingly.
OTOH, there's certainly potential to abuse the system, and I agree that if a single group has a monopoly on conducting trials in a given field, it could lead to problems.
Whether there really are such problems for HIV clinical research, I don't know. But Michael's claims of "no lives saved" and "a majority of deaths still due to the the AIDS drugs" make clear that he is at best highly ignorant on the subject, so I'm disinclined to take his word for any of it.
qetzal, in the following paragraph, I quote you yourself:
"Bad air, magical or satanic curses, evil spirits, mind control rays. Maybe it's as simple as the desire to assign a cause to everything. If we know the cause of something, we are in a better position to control and/or avoid it, which has obvious evolutionary advantages.
For those things that have no visible cause, an invisible one gets invented to satisfy the desire."
BRAVO QETZAL!!! Very well spoken! But perhaps you were trying to tell yourself something, as there is a saying "we teach what we most need to learn".
Do you want to get rich? Do you want to be powerful?
Don't walk, RUN! Get into hiv drug trial testing today:
http://www.shillfactor.net/controlresearch.html
Wow. I could ALMOST give some credence to some of Michael's warnings, if he weren't such a git immediately afterward. Qetzal's point is clearly made for the same reasons.
The Injury Of Objectivity
If I were to rate the corruptive tactics performed by big pharmaceutical companies, the intentional corruption of implementing fabricated and unreliable results of clinical trials would be at the top of the list. Pharmaceutical companies manipulate the trials they sponsor because of their power to control others involved in the process largely absent of regulation. This is a matter of requiring authenticity and, more importantly, assuring the safety of the public health.
Decades ago,clinical trials were conducted in academic settings that focused on the acquisition of knowledge and the completely objective discovery of novel medicine. Then, in 1980, the Bayh-Dole Act was created, which allowed for such places to profit off of their discoveries that were performed for pharmaceutical companies in the past. This resulted in the creation of for-profit sites, called Contract Research Organizations (CROs), which are composed of community research sites with questionable investigators void of necessary experience or quality regarding their research purpose and ability. Since they are for-profit, the trials conducted at CROs are sponsored by pharmaceutical companies that control and manipulate all aspects of the trial. This coercion is done by various methods of deception in subtle and tacit methods. As a result, research in this manner has been transformed into a method of marketing, which includes altered results of the trial to favor the sponsor's medication. Their activities are absent of true or applied regulation, and therefore have the autonomy to create whatever they want to benefit the collusive relationship between the site and the sponsor.
Further disturbing is that once the trials are completed, the medical articles are then written by ghostwriters, who are not identified and acknowledged by the sponsor, and are not trained in clinical research overall, as they are simply freelance writers. How often ghostwriters are utilized by pharmaceutical companies remains a mystery. This activity removes accountability and authenticity of the fabricated clinical trial even further. The corruptive act is finally completed by the sponsor hiring an author to be placed on the trial that likely had no involvement with the trial, and, along with others, was paid by the sponsor. To have the trial published, the sponsor pays a journal, along with the promise of purchasing thousands of reprints of the study from the journal. Again, how often this process is performed is unknown, yet frequent enough to create hundreds of such false writers and research sites to support the industry. So benefits of medicine studied in such a malicious way can potentially harm patients and their treatment options. The purchased reprints are distributed to the sponsor's sales force to share the content with prescribers -- your doctor.
Such misconduct impedes research and the scientific method with frightening ethical and harmful concerns. Our health care treatment with medications is now undetermined in large part in such situations, as well as the objectivity that has been intentionally eliminated regarding the trust in the scientific method in this type of activity illustrated in this article. More now than ever, meds that are removed from the market are given black box warnings. Now I understand why this is occurring.
The pharmaceutical industry needs transparency and disclosure in order to correct what we have historically relied upon for conclusive proof -- the scientific method. More importantly, research should not be conducted in a manner that the sponsor can interfere in the ways I described in this article. We should call for independent sites with absolutely no involvement with the drug maker. And clearly, regulation has to be enforced not selectively, but in a complete fashion. Public awareness would be a catalyst for this to occur, after initially experiencing a state of total disbelief that such operations actually are conducted by such people, of course. We can no longer be dependent on others for our optimal health.
Knowledge is power, and is also possibly a lifesaver.
Ethics and Science need to shake hands.
- Richard Cabot
Dan Abshear (published on www.brainblogger.com)
Author's note- Similar claims validate the above on www.plos.org