Harold C. Sox

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol.The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

We investigated how variations in the way information is presented to patients influence their choices between alternative therapies. Data were presented summarizing the results of surgery and radiation therapy for lung cancer to 238 ambulatory patients with different chronic medical conditions and to 491 graduate students and 424 physicians. We asked the subjects to imagine that they had lung cancer and to choose between the two therapies on the basis of both cumulative probabilities and life-expectancy data. Different groups of respondents received input data that differed only in whether or not the treatments were identified and whether the outcomes were framed in terms of the probability of living or the probability of dying. In all three populations, the attractiveness of surgery, relative to radiation therapy, was substantially greater when the treatments were identified rather than unidentified, when the information consisted of life expectancy rather than cumulative probability, and when the problem was framed in terms of the probability of living rather than in terms of the probability of dying. We suggest that an awareness of these effects among physicians and patients could help reduce bias and improve the quality of medical decision making.

The objective of clinical prediction rules is to reduce the uncertainty inherent in medical practice by defining how to use clinical findings to make predictions. Clinical prediction rules are derived from systematic clinical observations. They can help physicians identify patients who require diagnostic tests, treatment, or hospitalization. Before adopting a prediction rule, clinicians must evaluate its applicability to their patients. We describe methodological standards that can be used to decide whether a prediction rule is suitable for adoption in a clinician's practice. We applied these standards to 33 reports of prediction rules; 42 per cent of the reports contained an adequate description of the prediction rules, the patients, and the clinical setting. The misclassification rate of the rule was measured in only 34 per cent of reports, and the effects of the rule on patient care were described in only 6 per cent of reports. If the objectives of clinical prediction rules are to be fully achieved, authors and readers need to pay close attention to basic principles of study design.