The unobtainable placebo: control of independent clinical research by industry?

Abstract

Independent researchers might end up compromising—or even abandoning—their research design because of the unwillingness of some pharmaceutical companies to deliver placebo drugs or devices. We believe that this could be a major way for the pharmaceutical industry to control scientific information about their drugs. In an example known by us, a drug company was approached by researchers with the aim of obtaining placebo medication (in a specialised injection pen for patients with diabetes) for an independently financed trial to investigate the effect of a marketed drug. Before considering delivery of placebo, the company asked for a full protocol to be scrutinised by an opaque system of evaluation committees. After more than 6 months, the company finally agreed to supply placebo devices provided that the protocol was changed according to their suggestions. The researchers were also obliged to allow the company access to the resulting trial report for 4 weeks before submission for publication. In a second example, a drug company charged an extraordinary amount of money for providing a simple placebo tablet, effectively preventing the planned clinical trial from going ahead. In yet another example, the drug company plainly refused to deliver the placebo. We do not think these examples are unique. In the situations above, the only way forward short of compromising the design with an unblinded trial is to have the placebo manufactured elsewhere. This can be extremely costly and cumbersome1Curfman GD Morrissey S Drazen JM Products at risk.N Engl J Med. 2010; 363: 1763Crossref PubMed Scopus (9) Google Scholar—or even impossible. Is it acceptable that drug companies with an established placebo-manufacturing process (for their own marketing authorisation trials) can choose whether they wish to sell placebo to independent researchers? By contrast with publicly sponsored research, industry-sponsored research often focuses on profitable areas and future profits instead of areas where important health improvements could result.2Ferner RE Hughes DA The problem of orphan drugs.BMJ. 2010; 341: c6456Crossref PubMed Scopus (22) Google Scholar The industry's reluctance to do relevant head-to-head trials1Curfman GD Morrissey S Drazen JM Products at risk.N Engl J Med. 2010; 363: 1763Crossref PubMed Scopus (9) Google Scholar, 3Lathyris DN Patsopoulos NA Salanti G Ioannidis JPA Industry sponsorship and selection of comparators in randomized clinical trials.Eur J Clin Invest. 2010; 40: 172-182Crossref PubMed Scopus (70) Google Scholar contributes to the fact that the drug of interest is often found to be superior.4Als-Nielsen B Chen W Gluud C Kjaergard LL Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events?.JAMA. 2003; 290: 921-928Crossref PubMed Scopus (593) Google Scholar, 5Lexchin J Bero LA Djulbegovic B Clark O Pharmaceutical industry sponsorship and research outcome and quality: systematic review.BMJ. 2003; 326: 1167-1170Crossref PubMed Scopus (1560) Google Scholar These issues make independent clinical research highly necessary. In our opinion, the pharmaceutical industry has an obligation to provide placebo to match their marketed drugs without prior assessment and approval of protocols. This process would facilitate the generation of commercially unbiased research, possibly improve the life and welfare of patients, cut health costs, and help rebuild the credibility of the pharmaceutical industry. Unfortunately, the present situation shows that, without a legal obligation to provide placebos to match their marketed drugs, the pharmaceutical industry has de-facto control over drug trials. We thank Peter C Gøtzsche and Andreas Lundh for their thorough and critical appraisal of this letter. We declare that we have no conflicts of interest.