Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02120, USA.
N Engl J Med. 2012 Sep 20;367(12):1119-27. doi: 10.1056/NEJMsa1202397.
The effects of clinical-trial funding on the interpretation of trial results are poorly understood. We examined how such support affects physicians' reactions to trials with a high, medium, or low level of methodologic rigor.
We presented 503 board-certified internists with abstracts that we designed describing clinical trials of three hypothetical drugs. The trials had high, medium, or low methodologic rigor, and each report included one of three support disclosures: funding from a pharmaceutical company, NIH funding, or none. For both factors studied (rigor and funding), one of the three possible variations was randomly selected for inclusion in the abstracts. Follow-up questions assessed the physicians' impressions of the trials' rigor, their confidence in the results, and their willingness to prescribe the drugs.
The 269 respondents (53.5% response rate) perceived the level of study rigor accurately. Physicians reported that they would be less willing to prescribe drugs tested in low-rigor trials than those tested in medium-rigor trials (odds ratio, 0.64; 95% confidence interval [CI], 0.46 to 0.89; P=0.008) and would be more willing to prescribe drugs tested in high-rigor trials than those tested in medium-rigor trials (odds ratio, 3.07; 95% CI, 2.18 to 4.32; P<0.001). Disclosure of industry funding, as compared with no disclosure of funding, led physicians to downgrade the rigor of a trial (odds ratio, 0.63; 95% CI, 0.46 to 0.87; P=0.006), their confidence in the results (odds ratio, 0.71; 95% CI, 0.51 to 0.98; P=0.04), and their willingness to prescribe the hypothetical drugs (odds ratio, 0.68; 95% CI, 0.49 to 0.94; P=0.02). Physicians were half as willing to prescribe drugs studied in industry-funded trials as they were to prescribe drugs studied in NIH-funded trials (odds ratio, 0.52; 95% CI, 0.37 to 0.71; P<0.001). These effects were consistent across all levels of methodologic rigor.
Physicians discriminate among trials of varying degrees of rigor, but industry sponsorship negatively influences their perception of methodologic quality and reduces their willingness to believe and act on trial findings, independently of the trial's quality. These effects may influence the translation of clinical research into practice.
临床试验经费对试验结果的解读有何影响尚不清楚。我们研究了这种支持如何影响医生对方法学严谨程度不同的试验的反应。
我们向 503 名内科住院医师提供了我们设计的描述三种假设药物临床试验的摘要。这些试验具有较高、中等或较低的方法学严谨性,每个报告包括三种支持披露中的一种:制药公司的资助、NIH 资助或无资助。对于研究的两个因素(严谨性和资助),随机选择三种可能变化中的一种包含在摘要中。后续问题评估了医生对试验严谨性的印象、对结果的信心以及开处方的意愿。
269 名应答者(53.5%的应答率)准确地感知了研究严谨性的水平。医生报告说,他们不太愿意开低严谨性试验中测试的药物,而更愿意开中严谨性试验中测试的药物(比值比,0.64;95%置信区间[CI],0.46 至 0.89;P=0.008),并且更愿意开高严谨性试验中测试的药物,而不是中严谨性试验中测试的药物(比值比,3.07;95%CI,2.18 至 4.32;P<0.001)。与未披露资金相比,披露行业资金会导致医生降低试验的严谨性(比值比,0.63;95%CI,0.46 至 0.87;P=0.006)、对结果的信心(比值比,0.71;95%CI,0.51 至 0.98;P=0.04)和开处方的意愿(比值比,0.68;95%CI,0.49 至 0.94;P=0.02)。医生对行业资助试验中研究的药物的处方意愿是 NIH 资助试验中研究的药物的一半(比值比,0.52;95%CI,0.37 至 0.71;P<0.001)。这些影响在所有严谨性水平上都是一致的。
医生对不同严谨程度的试验进行区分,但行业赞助会对他们对方法学质量的看法产生负面影响,并降低他们相信和根据试验结果采取行动的意愿,而与试验的质量无关。这些影响可能会影响临床研究向实践的转化。