June 1991: Access vs. Answers
"There is, to be sure, an incredible irony in all this. Sick gay men, abandoned by a president who refused publicly to acknowledge their disease on all but one occasion, provided the shock troops to move forward his administration's deregulatory drug control program."
"The ddI expanded access program saved my life."
In the past year and a half, more than 20,000 people have received ddI through expanded access programs. Meanwhile, clinical trials of ddI have enrolled faster than trials for any other comparable antiviral therapy tested by the AIDS Clinical Trials Group (ACTG). This doesn't mean that tensions between the need to adequately characterize a new therapy and the need to provide treatment to people at high risk for severely debilitating disease and death have been resolved. Some activists continue to complain that the ddI expanded access program is overly restrictive and demand the drug's approval before clinical trials have been completed. Many doctors and regulators who have seen Bristol Myers-Squibb's NDA application have expressed doubt about the quality of the application.
This experience has initiated a debate about the importance of "Access vs. Answers," as though there were an essential conflict between allowing people for whom no approved therapy exists to access promising unproven medications and the conduct of sound scientific research on those medications. This is more a sign of the intellectual poverty of regulators, scientists and AIDS activists than an indication of any real dichotomy. The regulation of AIDS drugs, like the treatment of AIDS, must build on its experience; we must incorporate knowledge gained from the ddI experience into future attempts to resolve regulatory and trial design issues.
The need for ethical, well-designed trials that provide clear, quick answers has never been more pressing. Some have suggested that validation of new therapies takes so long as to be virtually useless. However, we cannot allow this crisis to eliminate requirements for sound efficacy evaluation. It is grossly unethical to require PWAs to make treatment decisions in an informational vacuum any longer than is absolutely necessary. While the FDA is often unresponsive and painfully slow, deregulation promises nothing more than a capitulation to life-or-death treatment decisions based on "drug of the month" anecdotes, an unacceptable solution to many of us who are fighting for our lives.
The unrecognized benefit of Expanded Access programs is that they provide the equivalent of a Phase Four post-marketing study coterminous with the randomized Phase II efficacy trials -- generating invaluable insights into the patterns of use and real-world toxicities likely to be encountered when the drug is taken by its intended population, with all its diversity and heterogeneity. While the FDA might be understandably reluctant to approve a drug which has only been taken by the small number of people in a controlled Phase II trial, proof that the drug is safe in a broad swaths of the real-world HIV population would provide significantly greater confidence, thus supporting an NDA.
The key to achieving faster drug development in AIDS lies not in an exclusive focus on Expanded Access or Parallel Tracks, but rather on their integration into an enlightened program of rapid, flexible, humane and attractive clinical trials.
The activists, regulators, and statisticians have provided the tools. It is up to industry, now, to use these tools to devise not only better treatments and prophylaxes, but a cure for AIDS within this decade.
This article was provided by Gay Men's Health Crisis. It is a part of the publication GMHC Treatment Issues. Visit GMHC's website to find out more about their activities, publications and services.