Robert Goldberg is one of the authors of DrugWonks. It is the blog of the Centers for Medicine in the Public Interest (CMPI), which debates today's drug policies.
Last week the FDA issued a statement essentially saying that it was not responsible for the dearth of new drug approvals in recent years. It would be easy to blame a more cautious agency responding to harsher Congressional oversight for the fact that the there has been both a decline in new drug approvals and an increase in approvable letters issued.
But the answer is not so simple. Pharmaceutical companies have reached the end of what can be produced from targets validated 15 to 20 years ago. The FDA is understaffed and overworked, and approvable letters are often used as a safety valve. Alternately, new drugs may have side effects that require the development of risk management plans and additional data collection.
In any event, the focus on the present is misplaced. So is the emphasis on the quantity of drugs and biologics in the pipeline. The more important questions are: How well will the future crop of drug candidates be validated? Will these drugs target specific groups of individuals based on biological markers of response and disease? Will the success rate increase--rather than decrease--over the next five years? Will time to market for those candidates decrease?
Ironically, it is here where Congress could have the most influence. When Senator Grassley claimed that no surrogate marker should be used to approve a drug, what he essentially said was that that the new science of personalized medicine should be scrapped in favor of waiting ten years until a new drug is approved. But if Grassley and others who favor what amounts to an anti-science approach to drug approvals had won the argument nearly two decades ago, many medicines for cancer and HIV that have cut the death rate of those diseases dramatically would just be hitting the market.
Congress is currently in a regulatory rage. The key to better drug development is not more bureaucrats or lawsuits, but a stronger scientific foundation for risk assessment, which is at the foundation of everything the FDA does. And genomics--not a stand-alone drug safety agency inside the FDA accountable only to Senator Grassley--should play a central role in building that scientific platform.
Following the Vioxx withdrawal, many demanded long and expensive post-market trials. But some drug developers have found a way to detect routine toxicity by literally getting the problem to turn on a blinking light in a genetic expression array from cells exposed to a prospective drug. Indeed, the goal of the Critical Path is to evaluate the safety and efficacy of medical products with the same science being used to discover how different pathways and polymorphisms shape our unique response to medicines and disease.
Drug approvals are declining because drug development is moving from the blockbuster model to a process of creating medicines of great benefit to a small group of patients with specific diseases. Many others will become orphan drugs with targeted--and limited--markets. This will lead to wider off-label use, since formal trials with every genetic sub-group that would benefit from a drug would be unreasonable, unnecessary and unethical. It will also lead to fewer DTC ads, as a fragmented market will make such methods less cost-effective.
Clinical trials will still have an important role in drug development. But their design and analysis can be made more fruitful by learning from failed clinical trials. Genetic evidence of different responses to medicines will force companies to mine such data in cooperative fashion as a way to confirm that a test for drug safety is as reliable as, say, blood typing.
Further, companies and the FDA will have to spend more time analyzing what happens when people are receiving treatment under real-world circumstances. The factors that make a treatment work at a genetic level won't be detected by large clinical trials. Therefore, post-approval clinical trials that follow human biology in the real world will optimize use, instead of the artificially controlled environment that drug experiments currently use. That's a more productive focus for legislation.
Hence, we should worry not about how many new drugs there are, but what kind of new medicines and when they arrive. Drug development can become safer, less expensive and more efficient. Medicines tailored to smaller groups would allow prescribing and reimbursement to be based on the true biogenetic and medical conditions of patients. There are many legislators and special interest groups who fear this future. They're the ones who favor more regulation at the FDA, which could hinder scientific breakthroughs. - Robert Goldberg