Showing papers by "Peter C Gøtzsche published in 2015"

The PRISMA Extension Statement for Reporting of Systematic Reviews Incorporating Network Meta-analyses of Health Care Interventions: Checklist and Explanations

Abstract: The PRISMA statement is a reporting guideline designed to improve the completeness of reporting of systematic reviews and meta-analyses. Authors have used this guideline worldwide to prepare their reviews for publication. In the past, these reports typically compared 2 treatment alternatives. With the evolution of systematic reviews that compare multiple treatments, some of them only indirectly, authors face novel challenges for conducting and reporting their reviews. This extension of the PRISMA (Preferred Reporting Items for Systematic Reviews and Metaanalyses) statement was developed specifically to improve the reporting of systematic reviews incorporating network meta-analyses.

SPIRIT 2013 Statement: defining standard protocol items for clinical trials

Abstract: 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.

Does long term use of psychiatric drugs cause more harm than good

Abstract: We could stop almost all psychotropic drug use without deleterious effect, says Peter C Gotzsche, questioning trial designs that underplay harms and overplay benefits. Allan H Young and John Crace disagree, arguing that evidence supports long term use

CONSORT 2010 Statement: Updated guidelines for reporting parallel group randomized trials

Abstract: R controlled trials, when appropriately designed, conducted, and reported, represent the gold standard in evaluating healthcare interventions. However, randomized trials can yield biased results if they lack methodological rigour.1 To assess a trial accurately, readers of a published report need complete, clear, and transparent information on its methodology and findings. Unfortunately, attempted assessments frequently fail because authors of many trial reports neglect to provide lucid and complete descriptions of that critical information.2–4 That lack of adequate reporting fuelled the development of the original CONSORT (Consolidated Standards of Reporting Trials) statement in 19965 and its revision five years later.6–8 While those statements See related editorial on page 892.

Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis

Abstract: Background Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed. This is an update of a previously published review. Objectives To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search 30 March 2015). We previously searched PubMed using the terms vaccin* AND cystic fibrosis (last search 30 May 2013). Selection criteria Randomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic fibrosis. Data collection and analysis The authors independently selected trials, assessed them and extracted data. Main results Six trials were identified. Two trials were excluded since they were not randomised and one old, small trial because it was not possible to assess whether is was randomised. The three included trials comprised 483, 476 and 37 patients, respectively. No data have been published from one of the large trials, but the company stated in a press release that the trial failed to confirm the results from an earlier study and that further clinical development was suspended. In the other large trial, relative risk for chronic infection was 0.91 (95% confidence interval 0.55 to 1.49), and in the small trial, the risk was also close to one. In the large trial, one patient was reported to have died in the observation period. In that trial, 227 adverse events (4 severe) were registered in the vaccine group and 91 (1 severe) in the control group. In this large trial of a vaccine developed against flagella antigens, antibody titres against the epitopes contained in the vaccine were higher in the vaccine group compared to the placebo group (P < 0.0001). Authors' conclusions Vaccines against Pseudomonas aeruginosa cannot be recommended.

Under-reporting of conflicts of interest among trialists: a cross-sectional study

Abstract: Objectives: To determine the prevalence of conflicts of interest (COIs) among Danish physicians who are authors of clinical drug trial reports and determine the extent of undisclosed COIs in trial publications. Design: Cross-sectional study. Setting: The 100 most recent drug trial reports with at least one Danish non-industry employed physician author published in a journal adhering to the International Committee of MedicalJournal Editors’ (ICMJE) manuscript guidelines. For each article, two observers independently extracted trial characteristics and the authors’ COIs. Disclosed COIs were compared to what was registered on the Danish Health and Medicines Authority’s public disclosure list. Participants: Trial authors who are Danish physicians. Main outcome measures: Number of disclosed and undisclosed COIs. Results: One observer screened 928 articles and two observers assessed 120 articles for eligibility. The 100 included trials were published from February 2011 to May 2013 and included 318 Danish non-industry employed authors. Eighty-six of the 318 authors (27%) reported one or more COIs in the journal article. We found undisclosed COIs for 40 of 318 authors (13%) related to the trial sponsor or manufacturer of trial drugs. Seventy-nine of 318 authors (25%) had undisclosed COIs related to competing companies manufacturing drugs for the same indication and 136 (43%) had undisclosed COIs with any drug manufacturer. Conclusions: Almost half of all authors had undisclosed COIs in clinical trials reported in journals adhering to the International Committee of Medical Journal Editors’ manuscript guidelines. Self-declared COIs cannot be trusted, but public registries may assist editors in ensuring that more COIs are being reported.

Mammography screening is harmful and should be abandoned

Abstract: Mammography screening is controversial and systematic reviews conducted by organisations with no conflicts of interest, such as the Nordic Cochrane Centre, theUSand theCanadianTaskForces, the Independent UK Panel and the Swiss Medical Board have found substantial problems with the randomised trials. It is therefore difficult to know what the true effect is. An additional problem is that trials are old. All but one started between 1963 and 1982, and back then, women did not receive much adjuvant therapy such as anti-hormonal treatment and chemotherapy. The introduction of effective drugs has reduced substantially the potential for screening to work. Screening can have no effect for women who, thanks to improved therapy, now live so much longer that they die of a heart attack before their breast cancer becomes life-threatening. Furthermore, as the effect of adjuvant therapy is largely independent of nodal status and other tumour characteristics, it works whether or not the cancer is detected ‘early’. An additional, crucial problem is that the assessment of cause of death is biased in favour of screening. I documented this in our Cochrane review, and more recently also in a meta-regression analysis of the trials (Figure 1). One would expect to see the greatest reduction in breast cancer mortality in those trials that were most effective in lowering the rate of nodepositive cancers in the screened group. This was indeed the case, but the regression predicts that a screening effectiveness of zero (i.e. the rate of node-positive cancers is the same in the screened group as in the control group) results in a 16% reduction in breast cancer mortality (95% confidence interval 9–23% reduction). This could only happen if there is bias, and further analyses showed that assessment of cause of death and of the number of cancers in advanced stages were both biased in favour of screening.

Screening with urinary dipsticks for reducing morbidity and mortality

Abstract: Background Urinary dipsticks are sometimes used for screening asymptomatic people, and for case-finding among inpatients or outpatients who do not have genitourinary symptoms. Abnormalities identified on screening sometimes lead to additional investigations, which may identify serious disease, such as bladder cancer and chronic kidney disease (CKD). Urinary dipstick screening could improve prognoses due to earlier detection, but could also lead to unnecessary and potentially invasive follow-up testing and unnecessary treatment. Objectives We aimed to quantify the benefits and harms of screening with urinary dipsticks in general populations and patients in hospitals. Search methods We searched the Cochrane Renal Group's Specialised Register to 8 September 2014 through contact with the Trials Search Co-ordinator using search terms relevant to this review. Selection criteria Randomised controlled trials and other study types that compared urinary dipstick screening with no dipstick screening were eligible for inclusion. We searched for studies that investigated the use of urinary dipsticks for detecting haemoglobin, protein, albumin, albumin-creatinine ratio, leukocytes, nitrite, or glucose, alone or in any combination, and in any setting. We planned to exclude studies conducted in patients with urinary disorders. Data collection and analysis It was planned that two authors would independently extract data from included studies and assess risk of bias using the Cochrane risk of bias tool. However, no studies met our inclusion criteria. Main results Literature searches to 8 September 2014 yielded 4298 records, of which 4249 were excluded following title and abstract assessment. There were 49 records (44 studies) eligible for full text assessment; of these 18 studies were not RCTs and 26 studies compared interventions or controls that were not relevant to this review. Thus, no studies were eligible for inclusion. Authors' conclusions We found no evidence to assess the benefits and harms of screening with urinary dipsticks, which remain unknown.

Commentary: Screening: a seductive paradigm that has generally failed us

Abstract: Screening healthy people has face value and great public and political appeal. It looks so simple, and yet screening is fraught with difficulties. These start already with the terminology, and common slogans like, ‘Catch the disease early, before it has produced any symptoms!’ are misleading on two counts. First, disease means lack of ease, which is not what we understand by being healthy; but people who work with screening tend to forget that they deal with healthy people. For example, women being invited to mammography screening are often called patients in scientific articles. The second error is the assumption that the disease is caught early. That is rarely the case, and breast cancer is again a good example. If we assume that the growth rate for a particular cancer is constant, then the women have harboured the cancer for 21 years on average before it is large enough to be detected by mammography screening. Finding precursors to cancer is of course an entirely different matter. Screening with flexible sigmoidoscopy identifies polyps and vaginal smear finds carcinoma in situ. A third problem with screening is that it always causes harm. Sometimes it also leads to benefits, and sometimes the benefits are sufficiently large to outweigh the harms. The main focus in screening trials should therefore be to quantify the harms, but this has rarely been the case, if ever. Screening trials focus on disease-specific mortality, which may seem natural, but it is the wrong outcome. Screening leads to overdiagnosis, and interventions that are beneficial for real patients can be lethal for healthy overdiagnosed people. Radiotherapy of overdiagnosed women may kill at least as many as those who are spared dying from breast cancer by attending breast screening. Total mortality should therefore be the primary outcome in screening trials of mortality, and Saquib et al. report a systematic review in this issue of the journal that aimed at clarifying whether screening lowers total mortality for diseases that carry a high disease-specific mortality. They focused on cancer, cardiovascular diseases, type 2 diabetes and chronic obstructive pulmonary disease. They did not find any screening trials for hypertension or chronic obstructive pulmonary disease. Disease-specific mortality was reduced with ultrasound for abdominal aortic aneurysm in men, mammography for breast cancer and faecal occult blood test and flexible sigmoidoscopy for colorectal cancer, but the risk ratio point estimates for allcause mortality were all very close to 1.00 (range 0.98–1.03). Screening proponents often say that disease-specific mortality is the right outcome, arguing that in order to show an effect on total mortality, trials would become unrealistically large. I believe this argument is invalid, for both scientific and ethical reasons. We do randomized trials in order to avoid bias, and our primary outcome should therefore not be a biased one. Drug interventions are usually more common in a screened group, and they tend to increase mortality for a variety of non-disease related reasons. From an ethical perspective, it is problematic to screen the whole population in a certain age group without knowing whether this makes people live longer, while knowing almost certainly that it makes people less happy. It took 50 years after the first randomized trial of mammography started before we knew what the psychological consequences are of the many false-positive findings. A specially designed questionnaire was developed using focus

Influence of mammography screening on use of mastectomies in Denmark.

Abstract: To the Editor, Invitations to breast screening and information from public authorities and cancer charities have often promised that screening leads to less invasive surgical therapy [1]. Since the...

Author's reply to Tovey and colleagues.

Abstract: The Cochrane editors rushed and published their rapid response the same day that my paper came out—a day before the Maudsley debate. 1 2 The editors wrote that my recommendations are based on inappropriate interpretation of the research, which they cannot know, because they haven’t read my …