Six pairs of things to celebrate on International Clinical Trials Day

The Editor has invited me to mark the occasion with a few words “on the development and/or impact of randomised trials over the last decade, or perhaps some thoughts about the future.” I do so here by citing some recent developments that give me cause for both pride about the present state of randomised controlled trials (RCTs) and optimism about their future. Respecting the sample size of James Lind’s trial and the space allotted me by the Editor, they appear in six pairs.

I designed my first randomised controlled trial (RCT) in 1967, the same year that Tom Chalmers suggested that sharing the unblinded interim results of the Coronary Drug Project with all its investigators was a bad idea [1]. PubMed lists 218 RCTs published that entire year, equivalent to just three days output in 2012. In 1967, we didn't have a lot to celebrate about RCTs beyond their elegant simplicity and the small band of heroes who were applying them to highly controversial questions such as: Might giving antihypertensive drugs to symptomless U.S. veterans with diastolic blood pressures between 115 and 129 mmHg do more good than harm [2]?
Forty-six years and half a million RCTs later, we have so much to celebrate about RCTs that we observe an annual International Trials Day on or about the 20 th of May, the day in 1747 that James Lind started giving daily doses of cider, sulphuric acid, acetic acid, sea water, two oranges plus a lemon, or nutmeg to six different pairs of scorbutic sailors with "putrid gums, the spots and lassitude, with weakness in the knees" [3].
The Editor has invited me to mark the occasion with a few words "on the development and/or impact of randomised trials over the last decade, or perhaps some thoughts about the future." I do so here by citing some recent developments that give me cause for both pride about the present state of RCTs and optimism about their future. Respecting the sample size of James Lind's trial and the space allotted me by the Editor, they appear in six pairs.

1.1.Patients are increasingly setting RCT agendas.
Patient groups are increasingly holding trialists' feet to the fire and forcing us to honour our obligations to them and their diseases, illnesses, predicaments, and other patient-relevant outcomes, rather than focusing only on our interests and those of the drug and device industries. Its most progressive form is seen in the James Lind Alliance [4], which "brings patients, carers and clinicians together to identify and prioritise the top 10 uncertainties, or 'unanswered questions' , about the effects of treatments that they agree are most important." 6.1.The Cochrane Collaboration continues to flourish. Generating the 'gold standard' for determining the effects of health care, its more than 28,000 dedicated people from over 100 countries have prepared, updated, and promoted the accessibility of over 5,000 Cochrane Reviews.

Competing interest
Dave Sackett has been wined, dined, supported, transported, and paid to speak by countless pharmaceutical firms for over 50 years, beginning with two research fellowships and interest-free loans that allowed him to stay to finish medical school. Dozens of his randomised trials have been supported in part (but never in whole) by pharmaceutical firms, who never received or analysed primary data and never had veto power over any reports, presentations, or publications of the results. He has twice worked as a paid consultant to advise pharmaceutical firms whether their products caused lethal side-effects; on both occasions he told them "yes." He has testified as an unpaid expert witness for a stroke victim who successfully sued a manufacturer of oral contraceptives, and as a paid expert in preparing individual suits against manufacturers of female hormones and NSAIDs and in class-action suits against manufacturers of prosthetic heart valves and oral contraceptives. He was paid by a pharmaceutical firm to develop "levels of evidence" for determining the causation of adverse drug reactions. His wife inherited and sold stock in a pharmaceutical company. While head of a division of medicine he enforced the banning of drug-detail personnel from clinical teaching units (despite the threat of withdrawal of drug industry funding for resident research projects). He received the Pharmaceutical Manufacturers' Association of Canada Medal of Honour (and cash) for "Contributions to Medical Science in Canada" for the decade 1984-1994. A recent award (the 2010 Gairdner-Wightman Award) was sponsored by the Canadian Government and 21 research bodies, provinces, and manufacturers.