Showing papers by "Peter C Gøtzsche published in 2001"

The Revised CONSORT Statement for Reporting Randomized Trials: Explanation and Elaboration

Abstract: Overwhelming evidence now indicates that the quality of reporting of randomized, controlled trials (RCTs) is less than optimal. Recent methodologic analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which boast the elimination of systematic error as their primary hallmark. Systematic error in RCTs reflects poor science, and poor science threatens proper ethical standards. A group of scientists and editors developed the CONSORT (Consolidated Standards of Reporting Trials) statement to improve the quality of reporting of RCTs. The statement consists of a checklist and flow diagram that authors can use for reporting an RCT. Many leading medical journals and major international editorial groups have adopted the CONSORT statement. The CONSORT statement facilitates critical appraisal and interpretation of RCTs by providing guidance to authors about how to improve the reporting of their trials. This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the CONSORT statement. The meaning and rationale for each checklist item are presented. For most items, at least one published example of good reporting and, where possible, references to relevant empirical studies are provided. Several examples of flow diagrams are included. The CONSORT statement, this explanatory and elaboration document, and the associated Web site (http://www.consort -statement.org) should be helpful resources to improve reporting of randomized trials.

Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment.

Abstract: Background Placebo treatments have been reported to help patients with many diseases, but the quality of the evidence supporting this finding has not been rigorously evaluated. Methods We conducted a systematic review of clinical trials in which patients were randomly assigned to either placebo or no treatment. A placebo could be pharmacologic (e.g., a tablet), physical (e.g., a manipulation), or psychological (e.g., a conversation). Results We identified 130 trials that met our inclusion criteria. After the exclusion of 16 trials without relevant data on outcomes, there were 32 with binary outcomes (involving 3795 patients, with a median of 51 patients per trial) and 82 with continuous outcomes (involving 4730 patients, with a median of 27 patients per trial). As compared with no treatment, placebo had no significant effect on binary outcomes, regardless of whether these outcomes were subjective or objective. For the trials with continuous outcomes, placebo had a beneficial effect, but the effect decreas...

An Analysis of Clinical Trials Comparing Placebo with No Treatment

Abstract: Background Placebo treatments have been reported to help patients with many diseases, but the quality of the evidence supporting this finding has not been rigorously evaluated. Methods We conducted a systematic review of clinical trials in which patients were randomly assigned to either placebo or no treatment. A placebo could be pharmacologic (e.g., a tablet), physical (e.g., a manipulation), or psychological (e.g., a conversation). Results We identified 130 trials that met our inclusion criteria. After the exclusion of 16 trials without relevant data on outcomes, there were 32 with binary outcomes (involving 3795 patients, with a median of 51 patients per trial) and 82 with continuous outcomes (involving 4730 patients, with a median of 27 patients per trial). As compared with no treatment, placebo had no significant effect on binary outcomes, regardless of whether these outcomes were subjective or objective. For the trials with continuous outcomes, placebo had a beneficial effect, but the effect decreased with increasing sample size, indicating a possible bias related to the effects of small trials. The pooled standardized mean difference was significant for the trials with subjective outcomes but not for those with objective outcomes. In 27 trials involving the treatment of pain, placebo had a beneficial effect, as indicated by a reduction in the intensity of pain of 6.5 mm on a 100-mm visual-analogue scale. Conclusions We found little evidence in general that placebos had powerful clinical effects. Although placebos had no significant effects on objective or binary outcomes, they had possible small benefits in studies with continuous subjective outcomes and for the treatment of pain. Outside the setting of clinical trials, there is no justification for the use of placebos. (N Engl J Med 2001;344:1594-602.)

Quality of Cochrane reviews: assessment of sample from 1998

Abstract: Objective: To assess the quality of Cochrane reviews. Design: Ten methodologists affiliated with the Cochrane Collaboration independently examined, in a semistructured way, the quality of reviews first published in 1998. Each review was assessed by two people; if one of them noted any major problems, they agreed on a common assessment. Predominant types of problem were categorised. Setting: Cyberspace collaboration coordinated from the Nordic Cochrane Centre. Studies: All 53 reviews first published in issue 4 of the Cochrane Library in 1998. Main outcome measure: Proportion of reviews with various types of major problem. Results: No problems or only minor ones were found in most reviews. Major problems were identified in 15 reviews (29%). The evidence did not fully support the conclusion in nine reviews (17%), the conduct or reporting was unsatisfactory in 12 reviews (23%), and stylistic problems were identified in 12 reviews (23%). The problematic conclusions all gave too favourable a picture of the experimental intervention. Conclusions: Cochrane reviews have previously been shown to be of higher quality and less biased on average than other systematic reviews, but improvement is always possible. The Cochrane Collaboration has taken steps to improve editorial processes and the quality of its reviews. Meanwhile, the Cochrane Library remains a key source of evidence about the effects of healthcare interventions. Its users should interpret reviews cautiously, particularly those with conclusions favouring experimental interventions and those with many typographical errors. What is already known on this topic Cochrane reviews are, on average, more systematic and less biased than systematic reviews published in paper journals Errors and biases also occur in Cochrane reviews What this study adds Too often, reviewers9 conclusions over-rated the benefits of new interventions Readers of Cochrane reviews should remain cautious, especially regarding conclusions that favour new interventions The Cochrane Collaboration has taken steps to improve the quality of reviews

House dust mite control measures for asthma.

Abstract: BACKGROUND The major allergen in house dust comes from mites. Chemical, physical and combined methods of reducing mite allergen levels are intended to reduce asthma symptoms in people who are sensitive to house dust mites. OBJECTIVES The objective of this review was to assess the effects of reducing exposure to house dust mite antigens in the homes of mite-sensitive asthmatics. SEARCH STRATEGY We searched the Cochrane Airways Group trials register, checked reference lists of articles and hand-searched Respiration (1980 to 1996) and Clinical and Experimental Allergy (1980 to 1996). The Cochrane Library is searched every three months. SELECTION CRITERIA Randomised trials of mite control measures vs placebo or no treatment in asthmatic people known to be sensitive to house dust mites. DATA COLLECTION AND ANALYSIS Two reviewers applied the trial inclusion criteria, assessed their quality and extracted the data independently. Study authors were contacted to clarify information. MAIN RESULTS Twenty-nine trials (939 patients in the analyses) were included, with two trials awaiting assessment. There was little difference in improvement of asthma between patients in experimental groups compared to control groups (relative risk 1.04, 95% confidence interval (95%CI) 0.83 to 1.31). Asthma symptom scores were also similar for the experimental and control groups (standardised mean difference (SMD) -0.07, 95% CI -0.35 to 0.22), however there was significant heterogeneity between studies p=0.015. This appears to have been due, in part, to the parallel group studies of physical treatments. These three studies (107 patients) showed a significant reduction in symptoms; SMD -0.44 (95% CI -0.83, -0.06) with no heterogeneity between the trials. No significant difference was noted for medication usage (SMD -0.14, 95%CI -0.43 to 0.15). Peak flow in the morning showed no significant difference between the experimental and the control groups (SMD 0.04, 95%CI -0.13 to 0.21). REVIEWER'S CONCLUSIONS Current chemical methods aimed at reducing exposure to house dust mite allergens seem to be ineffective and cannot be recommended as prophylaxis for mite sensitive asthmatics. Physical reduction methods may reduce asthma symptoms, but results of larger and more rigorous studies are required before any recommendations can be made concerning this approach.

Is the Placebo Powerless? An Analysis of Clinical Trials Comparing Placebo With no Treatment

Abstract: Background Placebo treatments have been reported to help patients with many diseases, but the quality of the evidence supporting this finding has not been rigorously evaluated. Methods We conducted a systematic review of clinical trials in which patients were randomly assigned to either placebo or no treatment. A placebo could be pharmacologic (e.g., a tablet), physical (e.g., a manipulation), or psychological (e.g., a conversation). Results We identified 130 trials that met our inclusion criteria. After the exclusion of 16 trials without relevant data on outcomes, there were 32 with binary outcomes (involving 3795 patients, with a median of 51 patients per trial) and 82 with continuous outcomes (involving 4730 patients, with a median of 27 patients per trial). As compared with no treatment, placebo had no significant effect on binary outcomes, regardless of whether these outcomes were subjective or objective. For the trials with continuous outcomes, placebo had a beneficial effect, but the effect decreas...

Reporting of outcomes in arthritis trials measured on ordinal and interval scales is inadequate in relation to meta-analysis.

Abstract: OBJECTIVES—To study whether the reporting of clinical outcomes in arthritis trials measured on ordinal and interval scales is adequate in relation to meta-analysis. METHODS—Systematic review of randomised trials of non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis. Optimal reporting was defined as data in the original ordered categories for global evaluation and pain, and as mean and SD for number of tender joints and grip strength, and if a visual analogue scale had been used to measure pain. RESULTS—A total of 144 trials were included. The median sample size was 60 patients. The quality of the reporting increased over time for three of the four variables. Global evaluation was optimally reported in 52 of the 127 trials (41%) in which it was recorded. Pain was optimally reported in 27 of 98 trials (28%), number of tender joints in 41 of 123 trials (33%), and grip strength in 34 of 124 trials (27%). Even if rather broad criteria are adopted, only about half of the data were reported in a potentially useful way for a meta-analysis. CONCLUSIONS—Arthritis trials have been reported inadequately in relation to meta-analysis. As most trials are underpowered, meta-analysis is indispensable and the deficit therefore needs urgent improvement. Investigators should specify a priori what constitutes an important treatment effect and report numbers of patients improved.

Debate on screening for breast cancer is not over.

Abstract: EDITOR—In a news item, Mayor described a historically controlled study from Sweden that claimed that screening with mammography reduced deaths from breast cancer by nearly two thirds.1 This was followed a week later by a comment in the Minerva section, which started off with the strong political message that the case for breast cancer screening programmes is now beyond debate and went on to speak about …

Office of NHS cancer screening programme misrepresents Nordic work in breast screening row

Abstract: EDITOR—In Mayor's news story in the issue of 27 October the office of the NHS cancer screening programme in the United Kingdom misrepresents our research entirely.1 The office says that our findings of more aggressive treatment of breast cancer among screened women are based on only two studies, classified as poor quality. They are not. Numbers of mastectomies as well as numbers of tumourectomies increase when women are screened. This finding is consistent and is based on all four of the seven screening trials that have published data on this, including the two medium quality trials from Canada and Malmo.2 The office …

[What is evidence-based medicine?].

Abstract: Evidence-based medicine is based on the best results from clinical and epidemiological research, which is combined with clinical experience and patient preferences. Questions of prognosis and harm are often best elucidated in large cohort studies. For other clinical questions the best evidence is usually found by systematic review of randomised trials, if possible in the form of meta-analyses. To make a diagnosis is, for example, not an aim in itself but a way to arrive at a prognosis and to suggest a treatment, provided this leads to a better prognosis. The most relevant, albeit rarely seen, test of a diagnostic method is a randomised trial. Evidence-based medicine will provide the best basis for evaluations of which interventions should be abandoned and which are effective and economically feasible. The use of evidence-based clinical guidelines will lead to more cost-effective treatments. It should be a national strategy that health care should be evidence-based.