Trials and tribulations: the ISIS experience

The ISIS trials group has grown slowly over the last ten years and now includes about 1000 collaborating hospitals worldwide. The original stimulus came from the thesis of a research student, Salim Yusuf, a newly qualified Rhodes Scholar from India. Yusuf's thesis (begun in 1976) examined methods of measuring infarct size quantitatively and paved the way to a preliminary trial of i.v. atenolol in 477 patients in Manchester and Oxford. Richard Peto was consulted about the statistical aspects of a trial design and pointed out that most clinical trials at that time were hopelessly inadequate in size to have the power reliably to ascertain the value of moderate but medically worthwhile treatments in many common conditions. We thus developed much larger collaboration, which still continues to grow. Dr Rory Collins joined the Oxford Cardiac Department and the CTSU in 1981 and now is the coordinator of the ISIS trials, and co-director with Richard Peto of the CTSU. Simple trials answer the questions rapidly and effectively. The mechanics of the trial do not hinder patient entry by participating doctors and nurses. The trials are mainly funded by industry, with 'priming' grants from the British Heart Foundation. Once the protocol is agreed the funding companies have no further input. The trials are planned and supervised by an international steering committee. Sir Richard Doll chairs the data monitoring committees. A brief overview of the three completed trials will be given, together with some peeps behind the scenes.