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Innovation through collaboration and confrontation

by David Williams

I commented earlier on how innovative models of collaboration among researchers are showing promise in accelerating drug discovery. The Myelin Repair Foundation’s Accelerated Research Model is a leading example of how challenging existing paradigms can yield impressive results.

If anything, the problems in drug development are worse. The FDA sometimes seems to speak out of both sides of its mouth, with high-level officials promulgating “podium policies” that encourage innovation, while mid-level reviewers want to see the same old thing. That’s why you still see widespread use of old endpoints with little clinical value, like the Hamilton Anxiety Scale.

HIV/AIDS is a good place to look for innovations that can be copied more widely. Early on, AIDS groups like ACT UP (”united in anger and committed to direct action“) undertook fairly extreme measures to pressure pharmaceutical companies, researchers, governments and clinicians into dropping business as usual practices and finding ways to move faster and more dramatically. As is often the case when there are extreme groups like ACT UP, it increased the willingness of the establishment to take more moderate groups seriously.

I’m struck by the success of HIV/AIDS activists in spurring research funding and changing how  bureaucracies work considering the stigma attached to homosexuality and intravenous drug use.

One of the more interesting organizations to arise from this activism is the Forum for Collaborative HIV Research, a group which I’ve consulted to for the past few years. The Forum brings together a diverse set of constituents that don’t normally collaborate: pharmaceutical companies, various branches of the federal government including FDA, CDC and NIH, academic researchers, health care providers and patient advocates. By bringing these groups together in a neutral forum–including competing pharmaceutical companies and their regulators– the Forum has been able to grapple with important issues that otherwise would be left unresolved.

For example, back in 1999 the Forum convened a meeting to review the scientific and logistical issues in the design and implementation of salvage therapy regimes in heavily pre-treated patients in whom anti-viral therapies were no longer working. Such patients were generally excluded from trials in favor of so-called treatment-naive patients in whom it’s easier to demonstrate whether a new drug is working. Of course the salvage patients are the ones who really need the new drugs, since they are out of options. The Forum’s activities led to the FDA issuing guidance on the inclusion of salvage patients in trials, and this guidance has been used in the development of new drugs. A related problem is that patients who’ve developed resistance to their therapies are also likely to quickly develop resistance to a new drug if they just receive one new drug at a time. The Forum helped devise protocol designs to allow clinical trial subjects to receive two new drugs while still preserving the ability to measure efficacy.

These issues could not have been addressed without a collaborative effort. Normally when a pharmaceutical company and FDA interact it’s in the context of a specific submission. Neither party can step outside of the narrow bounds of that regulatory review, even if the issue at hand may be related to an entire class of drugs or the interaction among multiple drugs. More recently, the Forum has been active in addressing the safety and other issues involved in the development of CCR5 antagonists. The Forum brought together all the companies developing these drugs with US and European regulators, the companies making the diagnostic tests that are used with the drugs, clinical trial cohorts, advocates and academics. The results of this effort may be apparent shortly when an FDA panel meets on Tuesday to discuss Pfizer’s CCR5 drug, maraviroc. Just this morning, FDA reviewers announced their initial, generally positive findings.

Meanwhile, more than 10 years after the Forum’s founding we’re yet to see counterparts emerge in other areas that could benefit from similar approaches, such as oncology. Innovation tends to occur when cross-disciplinary groups come together. In general individuals and organizations find it more comfortable and convenient to work in their own areas. Anti-trust, regulations,  competitive rivalries and inertia stand in the way of fuller, sustained collaboration.

We may need some more ACT UP types to confront us and shake us out of our complacency.

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