Pharma’s Cutting Edge

At the time of this post, this editorial from Avorn is free to the public.

I find myself strangely in agreement with the usually pedantic Dr. Avorn, who injects a needed dose of pragmatism into the drug-safety debate. As I’ve discussed in this space previously, the failure to detect drug safety signals is a systematic failure of postmarketing safety surveillance. Rare adverse events will remain hidden from detection in all but the largest pre-marketing programs, and even when studies provide adequate power to detect rare adverse events, rarely will the number of cases be sufficient to determine with any confidence a causal relationship to study drug. Uncommon but serious adverse events, like those associated with Vioxx use, require appropriate studies and responses to signals pre-marketing, but, just as importantly, they require careful attention in “real-world” patient studies after marketing to distinguish true drug-related adverse reactions from drug-associated “signals”.

The U.S. trails countries like the UK in its obligation to ensure the safety of its new medicines. It deserves better, and there are mechanisms in place that provide for better. The FDA’s Office of Drug Safety has indicated its interest in implementing and routinely using prospective surveillance systems., and it has taken preliminary steps in this direction If we had real leadership in the U.S. government, a comprehensive surveillance program would be in place already. But, as a large majority of Americans acknowledge, we do not. I’m still holding out hope that the U.S. will have a world-best surveillance program in place before the end of this decade.

I just had to write something about this, but rational thought escapes me. I’m flabbergasted by the jury’s decision in this case. It just makes no sense to me. If it makes sense to one of you, please do let the world know your reasoning. I’d have loved to hear the jury’s deliberations. I wish I could say I was confident the decision would be overturned on appeal, but I have no such confidence. The ruling will give reason for other companies to pursue royalties for drug products they “invented” after the innovator’s product was already in late clinical trials…unbelievable.

The US District Court of Appeals for the D.C. District yesterday published its opinion in Abigail Alliance v. FDA/HHS. Abigail Alliance seeks to broaden access to experimental drugs for terminally ill patients. They seek unfettered access to experimental drugs after Phase 1 for terminal conditions (the Alliance would have the patient’s doctor make the determination whether the condition is terminal). The Court’s opinion is attached. The Appeals Court ruled 2 to 1 to remand the case to the District Court for trial (the Court had earlier dismissed the case), citing the terminally ill patient’s right to due process under the Constitution as a basis for contesting FDA’s restricted access to such medicines.

The minority opinion, by Judge Griffith, disagrees with the due process argument: “Our Nation’s concept of ordered liberty, along with our traditions and history, do not call for courts to usurp the judgment of the scientific and medical communities, expressed through Congress and the Executive Branch, that science does not warrant allowing the early access to experimental drugs the Alliance demands.”

The decision also raises a host of practical issues to be faced by the District Court in applying the due process standard. Again, from Judge Griffith: “If a terminally ill patient has such a right, are patients with serious medical conditions entitled to the benefit of the same logic and corresponding access? If an indigent cannot afford potentially life-saving treatment, would the Constitution mandate access to such care under the right recognized by the majority? Can a patient access any drug (i.e., marijuana for medicinal purposes…if she believes, in consultation with a physician, it is potentially life-saving? Would the majority’s right guarantee access to federally-funded stem cell research and treatment? Perhaps most significantly, what potential must a treatment have in order for the Constitution to mandate access? Because the majority does not answer this last question, the District Court faces an impossible task on remand. The majority concludes that the District Court must ‘determine whether the FDA’s policy barring access to post-Phase I investigational new drugs by terminally ill patients is narrowly tailored to serve a compelling governmental interest…..’ As a preliminary matter, the majority never explains why the District Court must determine that the FDA has a compelling, narrowly tailored interest in preventing access to all [Court’s emphasis] drugs that have passed or will pass Phase 1. Under the majority’s facial approach, the District Court must examine every drug undergoing FDA testing and every drug that may ever undergo FDA testing. It must then evaluate whether the FDCA’s prohibition on access to unapproved drugs and corresponding exemptions for limited access serve a compelling interest and are narrowly tailored in light of all of the different potential risks and benefits of all experimental drugs and the needs of all terminally ill patients.” Read the rest of this entry »