Lessons from the glitazones

Abstract

Edwin Gale1Gale AE Lessons from the glitazones: a story of drug development.Lancet. 2001; 357: 1870-1875Summary Full Text Full Text PDF PubMed Scopus (254) Google Scholar attributes the difference between the placebo group and the treatment group in the glitazone trials as due to the progressive loss of glucose control rather than solely from the benefit of treatment with the hypoglycaemic agent. The inappropriate use of placebo controls in some clinical studies is an issue of continuing concern.In principle, we agree with Temple and Ellenberg's view2Temple R Ellenberg SS Placebo-controlled trials and active-control trials in the evaluation of new treatment, I: ethical and scientific issues.Ann Intern Med. 2000; 133: 455-463Crossref PubMed Scopus (687) Google Scholar on the use of placebo controls in clinical trials. They believe placebo control is inappropriate for disorders in which delay or omission of available treatments would increase mortality or irreversible morbidity in participants.Gale does not address two important issues. First, what are the ethics of doing such research; were the participants in the placebo-control group of the glitazone trials subjected to unnecessary risk? Second, what is the proper approach to doing and reporting on placebo control studies? For example, the FDA rules on trials involving hypoglycaemic drugs call for placebo-controlled studies and not approved existing therapies. As such, the sponsor of the studies was in accordance with the law in the dissemination of findings.In Canada, amendments to the Food and Drug regulations involving clinical trials call for sponsors of clinical trials to show that trials are done according to internationally agreed principles of good clinical practice.3Amendments to Canada's Food and Drug Regulations: clinical trials.Canada Gazette. 2000; 134: 227-263Google Scholar For research ethics boards, the challenge is whether or not such protocols should be granted approval. Edwin Gale1Gale AE Lessons from the glitazones: a story of drug development.Lancet. 2001; 357: 1870-1875Summary Full Text Full Text PDF PubMed Scopus (254) Google Scholar attributes the difference between the placebo group and the treatment group in the glitazone trials as due to the progressive loss of glucose control rather than solely from the benefit of treatment with the hypoglycaemic agent. The inappropriate use of placebo controls in some clinical studies is an issue of continuing concern. In principle, we agree with Temple and Ellenberg's view2Temple R Ellenberg SS Placebo-controlled trials and active-control trials in the evaluation of new treatment, I: ethical and scientific issues.Ann Intern Med. 2000; 133: 455-463Crossref PubMed Scopus (687) Google Scholar on the use of placebo controls in clinical trials. They believe placebo control is inappropriate for disorders in which delay or omission of available treatments would increase mortality or irreversible morbidity in participants. Gale does not address two important issues. First, what are the ethics of doing such research; were the participants in the placebo-control group of the glitazone trials subjected to unnecessary risk? Second, what is the proper approach to doing and reporting on placebo control studies? For example, the FDA rules on trials involving hypoglycaemic drugs call for placebo-controlled studies and not approved existing therapies. As such, the sponsor of the studies was in accordance with the law in the dissemination of findings. In Canada, amendments to the Food and Drug regulations involving clinical trials call for sponsors of clinical trials to show that trials are done according to internationally agreed principles of good clinical practice.3Amendments to Canada's Food and Drug Regulations: clinical trials.Canada Gazette. 2000; 134: 227-263Google Scholar For research ethics boards, the challenge is whether or not such protocols should be granted approval.