Cleophas R C, Cleophas T J
Faculty of Law, University of Rotterdam, The Netherlands.
Int J Clin Pharmacol Ther. 1999 Jan;37(1):1-7.
Studies that do not confirm their prior hypotheses, otherwise called "negative" studies, receive less interest from different parties including authors, editors and sponsors, and so, not to publish such studies is a common phenomenon. Opinions differ on whether or not this phenomenon introduces imprecision into the assessment of health research and care.
The current paper gives arguments against and in favor of publishing "negative" trials, and tries to give suggestions for a more balanced approach to this problem.
Arguments against publishing "negative" trials include: we need not publish erroneously "negative" trials; we need not publish a "negative" study out of worry that the favored treatment is inferior; full-length reports of "negative" trials devaluate the quality of literature, because the data are usually not so important, and generally receive little interest from readers, and so, not to publish them is a more or less "natural" matter of course. Arguments in favor of publishing "negative" trials include: no report reduces the flow of information because "negative" trials provide at least some evidence and balance against the overwhelming power of positive data readily accepted for publication; no report violates the promise to patient participants; studies that do not confirm prior hypotheses are especially important; not-publishing leads to unnecessary repetition of research. Initially, trials were frequently "negative" not only due to lack of power but also due to inappropriate hypotheses and poor designs. Currently, this is less so, and the issue of selective reporting, therefore, needs to be reassessed. Suggestions for a more balanced approach to the problem of selective reporting might include: careful planning before the trial begins, reduces the chance of biased and erroneously "negative" trials; any trial, "positive" or "negative", provides probabilities rather than truths; this notion does not explain away publication bias but does make it less of a problem; "negative" trials may not be appropriate for general journals but very relevant to specialist journals as well as other organs of specialist groups; ethical committees and trial review boards should address the issue of publishing as part of their function.
Data from properly executed trials should routinely be made available. However, we should not forget that the empirical observations provided by clinical trials, are statistically tested, and that statistics are based merely on probabilities. It means that we must consider a more philosophical attitude to clinical trial evidence in terms of acceptance that scientific truths are rarely absolute.
那些未证实其先前假设的研究，即所谓的“阴性”研究，受到包括作者、编辑和资助者在内的不同方面的关注较少，因此，不发表此类研究是一种常见现象。对于这种现象是否会给健康研究和医疗评估带来不准确性，各方观点不一。
本文提出了反对和支持发表“阴性”试验的论据，并试图针对这一问题给出一种更平衡的方法建议。
反对发表“阴性”试验的论据包括：我们无需发表错误的“阴性”试验；我们不必因担心所青睐的治疗方法较差而发表“阴性”研究；“阴性”试验的完整报告降低了文献质量，因为数据通常不那么重要，而且一般很少受到读者关注，所以不发表它们或多或少是“自然而然”的事情。支持发表“阴性”试验的论据包括：不报告减少了信息流通，因为“阴性”试验至少提供了一些证据，并能平衡易于被接受发表的大量阳性数据的影响力；不报告违背了对参与试验患者的承诺；未证实先前假设的研究尤为重要；不发表会导致不必要的重复研究。最初，试验常常是“阴性”的，这不仅是因为缺乏效力，还因为假设不当和设计不佳。目前情况有所改善，因此，需要重新评估选择性报告的问题。针对选择性报告问题采取更平衡方法的建议可能包括：试验开始前仔细规划，减少出现有偏差和错误的“阴性”试验的可能性；任何试验，无论是“阳性”还是“阴性”，提供的都是概率而非事实；这一观点虽不能消除发表偏倚，但能使其问题不那么严重；“阴性”试验可能不太适合综合性期刊，但对专业期刊以及专业团体的其他机构非常相关；伦理委员会和试验审查委员会应将发表问题作为其职能的一部分加以处理。
来自正确实施试验的数据应常规公开。然而，我们不应忘记，临床试验提供的实证观察结果经过了统计检验，而统计仅仅基于概率。这意味着我们必须以一种更具哲学性的态度看待临床试验证据，即认识到科学真理很少是绝对的。
