Subscribe to RSS feedGuest post: Sonia Shah: “FDA guts rules protecting human test subjects overseas”
Readers: It’s a week of all-star guest blog posts here at the Prescription Access Litigation blog, and we’re going overseas. Earlier this week, we brought you Sarah Rimmington of the consumer advocacy group, Essential Action, with a post on “the WHO’s negotiations on R&D and the developing world.
Today we bring you another great post by a Guest Blogger, Sonia Shah. Sonia is the author of “The Body Hunters: Testing New Drugs on the World’s Poorest Patients,” a book exposing the exploitation of patients in developing countries in pharmaceutical clinical trials with little or no oversight. It’s a peek into the all-too-real world that the book and movie The Constant Gardener addresses.
American drugmakers are increasingly turning to developing countries as sites for clinical trials testing new drugs or new uses for old drugs. Unfortunately, the protections in place for patients in many countries are scant, if not absent. Until recently, the Helsinki Declaration provided some protection for such patients — admittedly, it was often inadequate or underenforced, but it was better than nothing. Now the FDA has renounced the Helsinki Declaration, and the consequences for pharma’s “test subjects” are dire. But I’ll let Sonia Shah give you all the details….
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With hardly a word in the mainstream press, the FDA has gutted the rules restraining drug companies from exploiting clinical trial subjects in developing countries.
With 80 percent of clinical trials failing to recruit sufficient numbers of test subjects on deadline, drug companies increasingly export their trials to developing countries, where sick, undertreated patients abound. It’s faster, it’s cheaper, and it’s easier to conduct the placebo-controlled trials that companies and the FDA prefer. There is precious little oversight of these trials.
Unlike for domestic trials, the FDA does not require advance notice before drug companies take their trials outside US borders. And with 90 percent of trials failing to gain FDA approval, a massive number of trials are conducted, fail, and then vanish with no agency review at all—and little public record, if any at all.
Until now, the FDA’s sole requirement for these overseas trials is that they adhere to the Declaration of Helsinki (or local rules, on the off-chance that they are more stringent). Signed by the United States and 34 other countries in 1975, the Declaration of Helsinki consists of several dozen pithy principles to govern ethical research on humans, and is widely considered the gold-standard in research ethics. Crafted and updated by the World Medical Association, a group representing dozens of national physicians’ organizations from around the globe, the Declaration of Helsinki (DOH) urges that participants’ voluntary informed consent be obtained, that independent committees to review and oversee trials be used, that investigators prioritize their subjects’ well-being, that research subjects be assured access to the best health interventions identified in trials, and that their societies enjoy a “reasonable likelihood” of benefiting from the results of trials.
t’s not a perfect document. It’s very short. It’s a little vague. The FDA does not bother to enforce it. Even when they know of infractions—such as in Pfizer’s trial of the antibiotic Trovan in Nigeria, which not only failed to procure informed consent, but didn’t even have an oversight committee in place at the time of the trial—the FDA has done nothing and approved the drug anyway. We know of that particular trial’s violations only because the Washington Post exposed them several years later. In reporting for a book I wrote on clinical trials in developing countries, I similarly found many examples of trials clearly in violation of Helsinki provisions that were nevertheless reviewed and approved by the FDA.
The FDA has been agitating against the DOH since the late 1990s, when the World Medical Association strengthened the document’s restrictions on placebo-controlled trials, which an unlikely alliance of industry, public health and academic researchers angrily challenged. The strengthened DOH, the FDA’s medical director Robert Temple railed, “doesn’t look like a group of suggestions that are worth discussing.” Under pressure from the agency and drug companies, the World Medical Association diluted the objectionable language about placebo trials—cue the increasing vagueness—but by then the FDA was on the warpath. Just as President Bush opted out of international treaties on climate change and anti-ballistic missiles, in 2001, the FDA bucked two decades of its own precedents, and refused to adopt updated versions of the internationally sanctioned Declaration of Helsinki. That done, in 2004, the agency proposed dumping the DOH from its codes altogether, and on April 28 announced the it would indeed be summarily excised starting in October.
In its place, the FDA will incorporate “Good Clinical Practice” rules. Good clinical practice sounds, well, good, but these rules are no replacement for the Declaration of Helsinki. Unlike Helsinki, which describes ethical principles agreed upon by the international medical community, GCP rules are bureaucratic regulations crafted by regulatory authorities and drug industry trade groups, behind closed doors. They offer little by way of ethical precept. There is no injunction, for example, that research subjects be assured access to study drugs after trials end, or that their communities have a reasonable likelihood of enjoying the benefits of the research, principles of justice enshrined in the DOH.
The FDA’s move against the DOH is more than a symbolic change. With drug companies rushing to countries where the domestic regulatory infrastructure is weak at best—India, where Pfizer and GlaxoSmithKline have set up global clinical trial hubs being perhaps the prime example—and the FDA turning a blind eye, the business of protecting impoverished, sick, undertreated patients from exploitative experimentation falls almost entirely upon local people convened by clinics and hospitals to sit on FDA-required ethics committees. Theirs is a nearly impossible job, much of it shrouded in secrecy. Some, from India and South Africa, spoke to me, anonymously. They told me of how their clinics and hospitals desperately need the income drug-industry trials bring in. Of how, often, their bosses sit on the committees with them, pressuring members to approve as many experimental protocols as come in. They are overworked, underpaid, and poorly trained—if trained at all—in the principles of research ethics. Even the most courageous among them find it difficult to challenge problematic experiments and interrupt the flow of industry dollars.
And yet, they do, and when they do, they rely upon the only set of rules that their administrators and drug company clients consider legitimate: those backed by the FDA.
The last-stand oversight of local ethics committees has clearly been insufficient. A growing body of evidence, from anthropological research to case studies, suggests that the consent of trial subjects in many poor countries is uninformed, and worse, non-voluntary. Many clinical-trial companies openly promote the non-voluntariness of trial subjects in developing countries, not as a reason to conduct fewer trials, but to conduct more. (Specifically, they promote the low dropout rates, a telling signal of coercion.) Anecdotal evidence of the abrogation of the principles of justice—the lack of access to study drugs after trials end, the inaccessibility of the benefits of research, whether because of brand-name prices or the irrelevance of the resulting drug—abounds.
That’s how bad it has been with the Declaration of Helsinki on the books. What we don’t know is how many more violations have been averted by the nameless, faceless people sitting on ethics committees in developing countries, relying upon the strictures of the Declaration of Helsinki. There is no way to know how many times they’ve been able to extract guarantees, protections, and promises from industry researchers, or to amend experiments so that subjects’ rights and safety are better protected, thanks to the principles of the DOH.
All we can know is that come October, thanks to the FDA’s scrapping of the gold-standard in research ethics, their already difficult work will be made more so. The vulnerability of research subjects in developing countries—often the poorest, the sickest, those with the fewest options—can only grow more fraught.
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Thank you to Sonia Shah for writing this insightful piece on the FDA’s scrapping of the Helsinki Declaration. To learn more about Sonia’s books and articles, visit her website at soniashah.com
January 5th, 2009 at 8:52 pm
The Conversion of Our Protector
The Food and Drug Administration originated in its primitive form several decades ago to ensure the health and safety of the citizens of the United States in regards to what they consume that is provided to them by manufacturers for their intake. The one person who became the catalyst for the formation of the Food and Drug Administration was a socialist named Upton Sinclair, who was a writer. One particular book, while fictional, addressed the working conditions in a meat packaging company that were quite shockingly described by Upton in this book. While the author intended with composing this book, “The Jungle”, to address and focus for the benefit of the readers his paradigm regarding capitalism, the issue in his book regarding food safety is what caught the attention of the public, including the president, who was involved with the development of the Food and Drug Administration soon afterwards.
However, the purpose and function of the FDA seems to have changed the past few decades, as the FDA appears to have decided to ensure the health of the pharmaceutical industry instead of the public health. A new FDA commissioner who is willing to resurrect the apex of the FDA and its purpose may have a positive effect on the public’s health. As presently, there are disturbing flaws within the FDA.
One example is the large amounts of money the industry gives the FDA for various reasons created recently- amounts so large that this accounts, according to some, for about half of the FDA’s total income, although it is by definition a governmental administration. An example of stated reason for receiving such funds is due to the prescription drug user fee act, which began in 1992. Basically, the drug industry has been authorized and is now required to pay the FDA for faster approval of their pending medications after pharmaceutical companies submit a new drug application to the FDA. This act now accounts for nearly 50 percent of the FDA’s drug oversight budget through this operational funding given to them by those who the FDA is suppose to regulate for the safety of the public health. The FDA also accepts over a million dollars from the pharmaceutical industry to give their pending new drug a priority review of 6 months instead of a year, along with a created etiology for this urgency often, it has been reported.
Results of this relationship, which some have called collusive and pathologically intimate, this collaboration between the drug industry and the FDA, could be a contributing factor the progressive and recent approval of unsafe drugs, so it seems. This has been demonstrated by their removal of, or a labeling change, requiring what is known as a black box warning of such drugs, which means that the drug is basically on probation. The lack of regulation and monitoring required by the FDA of the pharmaceutical industry has resulted in such dangerous safety concerns. In addition, the FDA continues to validate what has been surmised by many regarding their financial support from the drug industry that appears to be reciprocal. The result of this relationship has resulted in less than optimal protection regarding the health of the public with pharmaceuticals made available to them.
The presumed intimacy between these two organizations, the pharmaceutical industry and the FDA, does in fact seem to continue to worsen. For example, and recently, the FDA considered supporting overtly this massive and necessary client of theirs, the pharmaceutical industry, to allow their promoters to discuss their products that may or may not have been approved by the FDA for particular disease states. Yet the FDA claims that this proposal would enhance the education and knowledge of the prescriber by the pharmaceutical representative of the marketer of a particular medication, which remarkably mirrors the premise and objective of this industry already. So this strategy, void of any protection of the public health and potential dangers associated with this practice, illustrates once again the present state of the FDA and its need for reform.
A prescriber, upon their own discretion, can in fact prescribe a drug off-label, but historically and legally, however, representatives from the pharmaceutical industry have been prohibited from suggesting indications assigned to their promoted drugs by the FDA. In fact, it is a federal offense for such representatives to speak off-label about the drugs they promote, and more pharmaceutical companies are and have been penalized for this activity in the form of large settlements paid by such pharmaceutical corporations in the past as determined by the department of justice.
This off-label FDA protocol for drug representatives that has been described and proposed by our FDA with presumed encouragement by the pharmaceutical industry is called, “Good Reprint Practices.” This absurd benefit for the pharmaceutical industry would have pharmaceutical sales representatives use what may not truly exist, which is truthful and authentic clinical trials illustrating any off label claim regarding their promoted medication to health care providers. It is believed that many clinical trials are biased if not manipulated, so this strategy that apparently adds comfort to this protocol is invalid. Additional trial deception may include such factors as ghostwriting and fabricated authors of such trials, and this is one of many concerns of this FDA protocol that has been, or is now being considered. These facts can be validated and have been discovered by others, so it appears the FDA did not take this into consideration when they did suggest this ridiculous and frightening authorization offered to their client, the pharmaceutical industry.
Furthermore, this proposal is flawed in that most pharmaceutical representatives lack necessary medical and clinical training to discuss aspects of clinical trials. Most drug representatives have little medical or clinical training in any objective way, and they are not hired with having such a background, usually. So this seems to further complicate the idea of this off-label concept proposed by the FDA due to the ignorance of the representatives to discuss such clinical matters. In addition, the relaxation of previous restrictions regarding off-label promotion could prove to be a catalyst for representatives of the pharmaceutical industry to further embellish statements to prescribers for their own benefit in regards to their promoted medications they present to them. In fact recently, a study by Sermo concluded that 90 percent of doctors want clinical evidence based medicine from educated and trained professionals instead of the typical pharmaceutical sales representatives that now exist. This study also concluded that around 80 percent of health care providers prefer not to interact with pharmaceutical representatives, yet still accept drug samples from them for their patients.
So, our previous safety association, the FDA, appears to be evolving into a possibly harmful association with the pharmaceutical industry by suggesting such practices that aggravate the existing situation with the lack of protection that was once offered and required from the FDA.
It is unbelievable this good reprint practices proposal ever came into existence, with the delusional fallacy that it would be of any benefit to patient health. Furthermore, this may complicate existing patient medication errors, such as in the elderly or dosing for children, complicated by the fact that many are unable to understand label instructions on their med. So there are enough problems with prescribing, and adding this FDA proposal would just make the situation worse. We as citizens are no longer the concern of the FDA, one could conclude, and this is clearly dangerous to the public’s health.
Perhaps another alternative would be to have clinically trained people discuss such issues regarding the benefits of medications with prescribers, instead of existing drug reps, who, unlike those academically enriched, have the objective of increasing the market share of their promoted meds with no regard to the science behind these meds, in large part. Because historically, medications have in fact proven to be beneficial for other disease states other than what a certain drug was initially indicated for upon approval. Yet this should not be determined by those who promote such drugs.
Regardless, awareness needs to happen by the citizens involving such tactics allowed by the FDA that are dangerous and deceptive. As citizens, we have the right to insist that the FDA, our FDA, maintains focus on the safety of the public and their health. Reform of the FDA appears to be necessary for this to occur to re-establish the FDA as an administration that was created for our protection.
About half of all drugs approved presently by the FDA have had serious post-approval side effects that should have already been known or suspected of these drugs. Well over 100 thousand people die every year from drug reactions or mistakes. Over 75 percent of drugs that are newly approved are very similar in efficacy, for example, as drugs that already exist and are available. This does not include the drugs that are approved that are simply direct to DVD sequels of existing medications in the same class. To complicate these issues, many of the ‘medical ailments’ in which others take drugs are often exaggerated and dubious, thanks to embellished promotion of these drugs, in large part, and this is largely un-regulated by the FDA, of course.
This seems to be a rather significant obstacle for those who are need to restore their health.
“Unlimited power is apt to corrupt the minds of those who possess it.” — William Pitt
Dan Abshear (author’s note: what has been written was based on information and belief)