Who Pays the Piper?

One of the principle aims of health care research is to understand the pathogenesis of disease and develop therapies that are evaluated objectively. The randomized controlled trial is held as the gold standard in assessing therapeutic benefit. Even with this rigorous approach, however, there are concerns that conflicts of interest may bias interpretation of data. In particular, there is some evidence that trials funded by profit organizations are more positive than the same intervention studied by nonprofit organizations. The implicit accusation in these findings is that “who pays the piper calls the tune.” Proton pump inhibitors (PPIs) are the most effective medical therapy for gastro-esophageal reflux disease (GERD) and it is unlikely that bias from pharmaceutically sponsored research accounts for this effect. A Cochrane systematic review identified 5 trials evaluating 635 patients with esophagitis comparing PPI therapy with placebo and all found the active therapy highly effective with a number needed to treat (NNT)=2 (95% confidence interval=1.4-2.5). There were also 26 trials involving 4064 esophagitis patients comparing PPI therapy with H2 receptor antagonists and all these were in favor of PPI with an overall NNT=3 (95% confidence interval =2.8-3.6). This is one of the most potent effects in clinical medicine and results are very consistent. It is, therefore, unlikely that drug company bias is having a large influence on these results. Some have argued that the pharmaceutical industry and academic clinicians have not always influenced the research agenda in a way that meets the demands of third party payers and patients. Certainly, all parties would like to know whether PPI therapy is effective in GERD. The research community has answered this question definitively with 3 Cochrane reviews, 225 trials involving over 55,000 participants. PPIs are also expensive and a significant proportion of most developed countries pharmacy budgets. Patients and third party payers would, therefore, also like to know whether PPIs are worth the money spent on them. One approach to answering this question is to estimate the impact of GERD symptoms on quality adjusted life years (QALYs) so that a cost/QALY can be calculated. Two trials have studied this and given QALY estimates varying between 0.69 and 0.94 in patients with GERD. This wide variation highlights the problems with measuring QALYs with different techniques giving different answers. In the absence of a gold standard it is hard to know which answer is the most accurate. The other approach is to elicit how much patients would be willing to pay for 1 month of cure from their GERD symptoms. This has been evaluated in one study and this suggested patients would be willing to pay $182 for 1 month cure of their symptoms with a drug with minimal side effects. There is a continual conflict in PPI prescribing between clinicians wanting to give the best drug to their patients and third party payers wanting to cut costs. The biomedical community has concentrated on efficacy and largely ignored other outcomes such as willingness to pay for symptom cure. We have 225 randomized controlled trials on the efficacy of PPI therapy and only 3 trials that directly address the value of PPI therapy to patients. It is time the biomedical community learnt to call for another tune.