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Is medical practice as clinical trial the tonic for the FDA and drug recalls?

Libertarians argue that the FDA prevents helpful drugs getting to market.  Pro-regulation types tend to argue that the FDA rushes drugs through too quickly allowing too many dangerous drugs on the market.  In the past few years, Phen-Fen, Rezulin and Baycol are just three drugs that have been pulled from the market because of adverse effects discovered well after Phase III trials were completed and the drugs approved for sale.

Besides the hidden human costs of restricting potentially helpful drugs from the market and the very visible human costs of not stopping potentially dangerous drugs getting to the market, there are real financial costs for the industry in not getting this right.  Bayer has already paid out over $450 million for damages caused by Baycol and is looking at something between $1bn and $5bn more to come–not to mention the loss of more than $1 billion in annual sales.  Just yesterday news started to surface that Avandia and Actos, both drugs for type-II diabetics may cause heart failure in some patients. There have also been serious suggestions that the other statins, Lipitor, Provachol and Zocor, don’t work and also have nasty side effects like Baycol. You can be sure that the attack-dog lawyers are just hoping that they can get their teeth into Pfizer, Merck, GSK and the rest over those issues. Yet we will see many, many more drugs coming to market over the next few years even before the flood of products from the genome revolution heads our way.

So what can we do to get out of this bind in which everyone loses but the lawyers?  One of the keys to this issue is that drugs work differently for different people. Clinical trials, even the big ones required for phase III, often exclude too many types of people who end up taking the drugs in the real world, or are not long enough to discover some of the long-term effects (the Baycol example). Phase IV clinical trials (those that happen after the drug is on the market) are expensive and really only used when the FDA demands them.

Some of the brighter people in the industry have been talking about a combination of silicon and genomics eventually solving this problem.  For one view, that of Kim Slocum at AstraZeneca, look at slides 75-95 of this long talk. I summarize Kim’s concept here (hopefully accurately!):

in the future we will understand the impacts of drugs on patients by recording their information electronically, matching it with their genetics, their treatment and their outcomes, and doing consistent long term monitoring and reporting of all of this information. Aggregated information from real care will then be collected, analyzed and delivered back to clinicians. This will eventually create a massive feedback loop that should show which drugs work best for which people over the long term. Inevitably this information will be incorporated into the drug development process, and the medical care process.

In other words drugs and their uses on different types of patients in the real world will become another facet of clinical trial research and of course another venue for FDA attention. In a meeting last year in direct response to my question Kim told me that he believed most of the pharma industry was on board with this new view of how pharmaceuticals should be used and monitored, despite its potential for showing up warts. Much like the related controversy over mistake-reporting, it would surely be better if we could see these types of systems in place, and find out the effects of pharmaceuticals before more drugs have to be pulled off the market in the face of human tragedies with only lawyers benefiting from the 20-20 hindsight.

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  1. The Human Injury of Lost 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 by pharmaceutical companies who manipulate these trials they sponsor because of their power to control others involved in such trials that is largely absent of regulation would be at the top of the list, and likely the most damaging to the requirement of authenticity and, more importantly, assuring the safety of the public health.
    Decades ago, clinical trials were conducted at academic settings that focused on the acquisition of knowledge and the completely objective discoveries of meds. 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 research trial sites, called Contract Research Organizations, which is often composed of community research sites with questionable investigators possibly void of necessary research experience or quality regarding their research purpose and ability. Since they are for- profit, with some CROs making billions of dollars a year. The trials conducted at such places are sponsored by pharmaceutical companies that control and manipulate all aspects of the trial being conducted involving their med being studied in 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 med. Their activities are absent of true or applied regulation, and therefore have the autonomy to create whatever they want to benefit what may be a collusive relationship between the site and the sponsor.
    Further disturbing is that once the creation of the trials is completed, they are then written by ghostwriters often, although no one seems to know how often. These people are not identified and acknowledged by the sponsor, and may not be trained in clinical research overall, as they are simply freelance writers, as one does not need research training or certification in order to perform this function. Rarely do trial ghostwriters question their instructions about their assignment, which is clearly deceptive and undocumented, as the mystery writers are known to make about 100 grand a year. This activity removes accountability and authenticity of the possibly 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 for doing this deceptive act.
    To have the trial published, the sponsor pays a journal to do this, along with the promise of purchasing thousands of reprints of their 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 pharmaceutical industry. So benefits of meds studied in such a malicious way potentially can harm patients and their treatment options and safety risks. The purchased reprints are distributed to the sponsor’s sales force to share the content with prescribers.
    Such misconduct discussed so far impedes research and the scientific method with frightening ethical and harmful concerns. Our health care treatment with meds is now undetermined in large part with such corruptive situations, as well as the possible absence of objectivity that has been intentionally eliminated. Trust in the scientific method in this type of activity illustrated in this article is absent. More now than ever, meds are removed from the market are given black box warnings. Now I understand why this is occurring.
    Transparency and disclosure needs to happen with the pharmaceutical industry for reasons such as this as well as many others, in order to correct what we have historically relied upon for conclusive proof, which is the scientific method. More importantly, research should not be conducted in a way that the sponsor can interfere in such ways described in this article, requiring independent sites with no involvement with the drug maker. And clearly, regulation has to be enforced not selectively, but in a complete fashion regarding such matters. 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

  2. I think one of the reasons that the FDA is so quick to approve drugs that later are found to be harmful is because the studies are done by the pharmaceutical companies themselves rather than independent laboratories. So, even though double-blind studies may be conducted, the researchers are not blind to the name of the drug company involved and who, in the end, pays for their salaries.
    A lot of people are now moving over to preventative health measures and are re-investigating some natural or herbal remedies that have worked very well for sometimes centuries. There’s a new “herbal whole body health treatment” that has, as its main curative ingredient, marine phytoplankton. It works on the principle that the body is quite capable of repairing itself in many cases if we just give it the right building blocks or nutrients. Marine phytoplankton, the original one-celled herbal life form occurring on the planet Earth, contain virtually all of the nutrients necessary for healthy animal life.
    While we most certainly need some of the pharmaceutically produced medications for handling intense pain there is more and more evidence pointing to the conclusion that natural formulations designed for whole body health often offer a much higher level of efficacy than do pharmaceuticals designed to tackle one specific problem.