Education And Debate

Registration of drugs for treating cancer and HIV infection: a plea to carry out phase 3 trials before admission to the market

BMJ 1995; 310 doi: (Published 20 May 1995) Cite this as: BMJ 1995;310:1305
  1. P P Koopmans, clinical pharmacological assessor to Dutch Medicines Evaluation Boarda
  1. a Department of Medicine, Division of General Internal Medicine and Department of Clinical Pharmacology, University Hospital Nijmegen, St Radboud, PO Box 9101, 6500 HB Nijmegen, Netherlands

    Drugs for cancer and HIV infection tend to be admitted to the market on the basis of results from phase 2 trials. Assessing the benefit-risk balance with phase 2 trials often is difficult—the effect of the drug is usually temporary; the correlation between response or improvement of clinical measurements and the patient's wellbeing is often poor; and the side effects of drugs for these fatal diseases are serious. Therefore, although sometimes difficult to conduct, comparative trials that use standard treatment, placebos, or best supportive care remain the corner-stone for reliably assessing the benefit-risk balance.

    The common criterion of drug regulatory committees for registration of a drug is that efficacy and safety have been shown in extensive pharmaceutical, pharmacological, toxicological, and clinical studies. Usually the clinical aspects of a drug are studied in phase 1, 2, and 3 trials, but whether all three phases are necessary for the registration of drugs for cancer and HIV infection is a matter of debate in Europe and the United States.

    The media, the pharmaceutical industry, and the patients involved all put pressure on the drug regulatory authorities to accelerate the procedures and to relax the criteria for admitting oncolytics and drugs against HIV infection to the market. They argue that the three phases of clinical trials are time consuming and may withhold a potentially valuable drug from the patient for too long, and that this requirement is therefore not ethical. They advocate early registration if it appears from phase 2 trials that a tumor is responding and the outcome of the patients is better than that of historical controls; for such drugs phase 3 trials, in which the drug is compared with standard treatment, placebo, or untreated controls, can be omitted or done after marketing. They also say that drugs for HIV infection should …

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