Peter C Gøtzsche

Bio: Peter C Gøtzsche is an academic researcher from Cochrane Collaboration. The author has contributed to research in topics: Systematic review & Placebo. The author has an hindex of 90, co-authored 413 publications receiving 147009 citations. Previous affiliations of Peter C Gøtzsche include University of Copenhagen & Copenhagen University Hospital.

General health checks in adults for reducing morbidity and mortality from disease

Abstract: General health checks involve multiple tests in a person who does not feel ill with the purpose of finding disease early, preventing disease from developing, or providing reassurance. Health checks are a common element of health care in some countries. To many people health checks intuitively make sense, but experience from screening programmes for individual diseases have shown that the benefits may be smaller than expected and the harms greater. One possible harm from health checks is the diagnosis and treatment of conditions that were not destined to cause symptoms or death. Their diagnosis will, therefore, be superfluous and carry the risk of unnecessary treatment. The authors identified 16 randomised trials which had compared a group of adults offered general health checks to a group not offered health checks. Results were available from 14 trials, including 182,880 participants. Nine trials studied the risk of death and included 155,899 participants and 11,940 deaths. There was no effect on the risk of death, or on the risk of death due to cardiovascular diseases or cancer. We did not find an effect on the risk of illness but one trial found an increased number of people identified with high blood pressure and high cholesterol, and one trial found an increased number with chronic diseases. One trial reported the total number of new diagnoses per participant and found a 20% increase over six years compared to the control group. No trials compared the total number of new prescriptions but two out of four trials found an increased number of people using drugs for high blood pressure. Two out of four trials found that health checks made people feel somewhat healthier, but this result is not reliable. They did not find that health checks had an effect on the number of admissions to hospital, disability, worry, the number of referrals to specialists, additional visits to the physician, or absence from work, but most of these outcomes were poorly studied. None of the trials reported on the number of follow-up tests after positive screening results, or the amount of surgery used. One reason for the apparent lack of effect may be that primary care physicians already identify and intervene when they suspect a patient to be at high risk of developing disease when they see them for other reasons. Also, those at high risk of developing disease may not attend general health checks when invited. Most of the trials were old, which makes the results less applicable to today's settings because the treatments used for conditions and risk factors have changed. With the large number of participants and deaths included, the long follow-up periods used in the trials, and considering that death from cardiovascular diseases and cancer were not reduced, general health checks are unlikely to be beneficial.

Recommendations by Cochrane Review Groups for assessment of the risk of bias in studies

Abstract: Assessing the risk of bias in individual studies in a systematic review can be done using individual components or by summarizing the study quality in an overall score. We examined the instructions to authors of the 50 Cochrane Review Groups that focus on clinical interventions for recommendations on methodological quality assessment of studies. Forty-one of the review groups (82%) recommended quality assessment using components and nine using a scale. All groups recommending components recommended to assess concealment of allocation, compared to only two of the groups recommending scales (P < 0.0001). Thirty-five groups (70%) recommended assessment of sequence generation and 21 groups (42%) recommended assessment of intention-to-treat analysis. Only 28 groups (56%) had specific recommendations for using the quality assessment of studies analytically in reviews, with sensitivity analysis, quality as an inclusion threshold and subgroup analysis being the most commonly recommended methods. The scales recommended had problems in the individual items and some of the groups recommending components recommended items not related to bias in their quality assessment. We found that recommendations by some groups were not based on empirical evidence and many groups had no recommendations on how to use the quality assessment in reviews. We suggest that all Cochrane Review Groups refer to the Cochrane Handbook for Systematic Reviews of Interventions, which is evidence-based, in their instructions to authors and that their own guidelines are kept to a minimum and describe only how methodological topics that are specific to their fields should be handled.

Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports.

Abstract: Objective To study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors. Design Systematic review and meta-analysis. Main outcome measures Mortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia. Data sources Clinical study reports for duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine obtained from the European and UK drug regulators, and summary trial reports for duloxetine and fluoxetine from Eli Lilly’s website. Eligibility criteria for study selection Double blind placebo controlled trials that contained any patient narratives or individual patient listings of harms. Data extraction and analysis Two researchers extracted data independently; the outcomes were meta-analysed by Peto’s exact method (fixed effect model). Results We included 70 trials (64 381 pages of clinical study reports) with 18 526 patients. These trials had limitations in the study design and discrepancies in reporting, which may have led to serious under-reporting of harms. For example, some outcomes appeared only in individual patient listings in appendices, which we had for only 32 trials, and we did not have case report forms for any of the trials. Differences in mortality (all deaths were in adults, odds ratio 1.28, 95% confidence interval 0.40 to 4.06), suicidality (1.21, 0.84 to 1.74), and akathisia (2.04, 0.93 to 4.48) were not significant, whereas patients taking antidepressants displayed more aggressive behaviour (1.93, 1.26 to 2.95). For adults, the odds ratios were 0.81 (0.51 to 1.28) for suicidality, 1.09 (0.55 to 2.14) for aggression, and 2.00 (0.79 to 5.04) for akathisia. The corresponding values for children and adolescents were 2.39 (1.31 to 4.33), 2.79 (1.62 to 4.81), and 2.15 (0.48 to 9.65). In the summary trial reports on Eli Lilly’s website, almost all deaths were noted, but all suicidal ideation events were missing, and the information on the remaining outcomes was incomplete. Conclusions Because of the shortcomings identified and having only partial access to appendices with no access to case report forms, the harms could not be estimated accurately. In adults there was no significant increase in all four outcomes, but in children and adolescents the risk of suicidality and aggression doubled. To elucidate the harms reliably, access to anonymised individual patient data is needed.

Ghost Authorship in Industry-Initiated Randomised Trials

Abstract: Background Ghost authorship, the failure to name, as an author, an individual who has made substantial contributions to an article, may result in lack of accountability. The prevalence and nature of ghost authorship in industry-initiated randomised trials is not known. Methods and Findings We conducted a cohort study comparing protocols and corresponding publications for industry-initiated trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg in 1994–1995. We defined ghost authorship as present if individuals who wrote the trial protocol, performed the statistical analyses, or wrote the manuscript, were not listed as authors of the publication, or as members of a study group or writing committee, or in an acknowledgment. We identified 44 industry-initiated trials. We did not find any trial protocol or publication that stated explicitly that the clinical study report or the manuscript was to be written or was written by the clinical investigators, and none of the protocols stated that clinical investigators were to be involved with data analysis. We found evidence of ghost authorship for 33 trials (75%; 95% confidence interval 60%–87%). The prevalence of ghost authorship was increased to 91% (40 of 44 articles; 95% confidence interval 78%–98%) when we included cases where a person qualifying for authorship was acknowledged rather than appearing as an author. In 31 trials, the ghost authors we identified were statisticians. It is likely that we have overlooked some ghost authors, as we had very limited information to identify the possible omission of other individuals who would have qualified as authors. Conclusions Ghost authorship in industry-initiated trials is very common. Its prevalence could be considerably reduced, and transparency improved, if existing guidelines were followed, and if protocols were publicly available.

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 is to assess the effects of reducing exposure to house dust mite antigens in the homes of mite-sensitive asthmatics, assessing chemical and physical methods separately and together. 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. Nine trials assessed chemical methods alone, 15 physical methods alone, and 5 a combination of chemical and physical methods. Overall, there was no statistically significant difference improvement of asthma (relative risk 1.04, 95% confidence interval 0.83 to 1.31), asthma symptom scores (standardised mean difference -0.07, 95% confidence interval -0.35 to 0.22), medication usage (standardised mean difference -0.14, 95% confidence interval -0.43 to 0.15), or peak flow in the morning (standardised mean difference 0.04, 95% confidence interval -0.13 to 0.21). For chemical methods used alone, there was a statistically significantly adverse effect on symptoms (P = 0.03), whereas for physical methods used alone as evaluated in parallel group trials, there was a statistically significant beneficial effect (P = 0.02). However, because of the large number of significance tests we performed, two significant results would be expected to occur by chance. Reviewers' conclusions Currently available evidence from controlled trials of chemical and physical approaches to reducing exposure to house dust mite antigens in the homes of mite-sensitive asthmatics does not provide a secure basis for advice and policy. Further trials one of them very large - are currently in progress. The additional evidence from these studies will help to clarify whether or not the substantial efforts required to implement strategies intended to reduce mites can be expected to yield beneficial effects of a magnitude that people with mite sensitive asthma consider worthwhile.

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

Abstract: David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement.

Abstract: Systematic reviews and meta-analyses have become increasingly important in health care. Clinicians read them to keep up to date with their field,1,2 and they are often used as a starting point for developing clinical practice guidelines. Granting agencies may require a systematic review to ensure there is justification for further research,3 and some health care journals are moving in this direction.4 As with all research, the value of a systematic review depends on what was done, what was found, and the clarity of reporting. As with other publications, the reporting quality of systematic reviews varies, limiting readers' ability to assess the strengths and weaknesses of those reviews. Several early studies evaluated the quality of review reports. In 1987, Mulrow examined 50 review articles published in 4 leading medical journals in 1985 and 1986 and found that none met all 8 explicit scientific criteria, such as a quality assessment of included studies.5 In 1987, Sacks and colleagues6 evaluated the adequacy of reporting of 83 meta-analyses on 23 characteristics in 6 domains. Reporting was generally poor; between 1 and 14 characteristics were adequately reported (mean = 7.7; standard deviation = 2.7). A 1996 update of this study found little improvement.7 In 1996, to address the suboptimal reporting of meta-analyses, an international group developed a guidance called the QUOROM Statement (QUality Of Reporting Of Meta-analyses), which focused on the reporting of meta-analyses of randomized controlled trials.8 In this article, we summarize a revision of these guidelines, renamed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), which have been updated to address several conceptual and practical advances in the science of systematic reviews (Box 1). Box 1 Conceptual issues in the evolution from QUOROM to PRISMA

Bias in meta-analysis detected by a simple, graphical test

Abstract: Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews . Main outcome measure: Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. Results: In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. Conclusions: A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution. Key messages Systematic reviews of randomised trials are the best strategy for appraising evidence; however, the findings of some meta-analyses were later contradicted by large trials Funnel plots, plots of the trials9 effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials Funnel plot asymmetry was found in 38% of meta-analyses published in leading general medicine journals and in 13% of reviews from the Cochrane Database of Systematic Reviews Critical examination of systematic reviews for publication and related biases should be considered a routine procedure