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Peter C Gøtzsche

Publications and source records attributed to Peter C Gøtzsche.

At least 19 recordsLinked to original sources
PubMed2007

Ghost authorship in industry-initiated randomised trials.

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.

Authorship↗
PubMed2006

[Cochrane reviews compared with industry-supported and other meta-analyses of the same drugs--secondary publication].

24 Cochrane reviews were compared with other, closely matched, meta-analyses of the same drugs. The quality score was highest for Cochrane reviews (7 vs. 2, p < 0.01). Of 8 industry-supported reviews, 7 with conclusions all recommended the experimental drug without reservations, compared with none of the Cochrane reviews (p = 0.02) although the estimated treatment effect was similar on average (p = 0.64). Industry-supported reviews were less transparent, had few reservations about methodological limitations of the included trials, and should be read with caution.

English Abstract↗
PubMed2006

Cochrane reviews compared with industry supported meta-analyses and other meta-analyses of the same drugs: systematic review.

OBJECTIVE: To compare the methodological quality and conclusions in Cochrane reviews with those in industry supported meta-analyses and other meta-analyses of the same drugs. DESIGN: Systematic review comparing pairs of meta-analyses that studied the same two drugs in the same disease and were published within two years of each other. DATA SOURCES: Cochrane Database of Systematic Reviews (2003, issue 1), PubMed, and Embase. DATA EXTRACTION: Two observers independently extracted data and used a validated scale to judge the methodological quality of the reviews. RESULTS: 175 of 1596 Cochrane reviews had a meta-analysis that compared two drugs. Twenty four meta-analyses that matched the Cochrane reviews were found: eight were industry supported, nine had undeclared support, and seven had no support or were supported by non-industry sources. On a 0-7 scale, the median quality score was 7 for Cochrane reviews and 3 for other reviews (P < 0.01). Compared with industry supported reviews and reviews with undeclared support, Cochrane reviews had more often considered the potential for bias in the review--for example, by describing the method of concealment of allocation and describing excluded patients or studies. The seven industry supported reviews that had conclusions recommended the experimental drug without reservations, compared with none of the Cochrane reviews (P = 0.02), although the estimated treatment effect was similar on average (z = 0.46, P = 0.64). Reviews with undeclared support and reviews with not for profit support or no support had conclusions that were similar in cautiousness to the Cochrane reviews. CONCLUSIONS: Industry supported reviews of drugs should be read with caution as they were less transparent, had few reservations about methodological limitations of the included trials, and had more favourable conclusions than the corresponding Cochrane reviews.

Bias↗
PubMed2006

[Noninferiority and equivalence randomized trials: lessons and reservations--secondary publication].

A noninferiority trial seeks to determine, whether a new intervention is not inferior to a reference intervention within a prespecified noninferiority interval (-Delta to 0) for the primary outcome. An equivalence trial aims to determine whether two interventions have a similar effect within a prespecified interval (-Delta to +Delta). These trials are controversial and difficult to grasp and very often poorly reported and conducted. Any claims regarding efficacy of new treatments, based on these trials, should be interpreted with caution, and it should be noted that Delta is often far too large to be clinically meaningful.

English Abstract↗
PubMed2006

Fungal infection-related mortality versus total mortality as an outcome in trials of antifungal agents.

BACKGROUND: Disease specific mortality is often used as outcome rather than total mortality in clinical trials. This approach assumes that the classification of cause of death is unbiased. We explored whether use of fungal infection-related mortality as outcome rather than total mortality leads to bias in trials of antifungal agents in cancer patients. METHODS: As an estimate of bias we used relative risk of death in those patients the authors considered had not died from fungal infection. Our sample consisted of 69 trials included in four systematic reviews of prophylactic or empirical antifungal treatment in patients with cancer and neutropenia we have published previously. RESULTS: Thirty trials met the inclusion criteria. The trials comprised 6130 patients and 869 deaths, 220 (25%) of which were ascribed to fungal infection. The relative risk of death was 0.85 (95% CI 0.75-0.96) for total mortality, 0.57 (95% CI 0.44-0.74) for fungal mortality, and 0.95 (95% CI 0.82-1.09) for mortality among those who did not die from fungal infection. CONCLUSION: We could not support the hypothesis that use of disease specific mortality introduces bias in antifungal trials on cancer patients as our estimate of the relative risk for mortality in those who survived the fungal infection was not increased. We conclude that it seems to be reliable to use fungal mortality as the primary outcome in trials of antifungal agents. Data on total mortality should be reported as well, however, to guard against the possible introduction of harmful treatments.

Antifungal Agents↗
PubMed2006

[Are relative risks and odds ratios in abstracts believable? Secondary publication].

The first result in 520 abstracts that reported relative risks or odds ratios was statistically significant in 70% of the randomized trials, 84% of cohort studies and 84% of case-control studies. Many results were derived from subgroup or secondary analyses or biased selection of results. The distribution of p values in the interval 0.04-0.06 was extremely skewed for trials, but most of the significant results were wrong, very doubtful, or could be discussed. The skewness was even larger in observational studies. This study shows that significant results reported in abstracts should be interpreted with great caution.

English Abstract↗
PubMed2006

Believability of relative risks and odds ratios in abstracts: cross sectional study.

OBJECTIVE: To compare the distribution of P values in abstracts of randomised controlled trials with that in observational studies, and to check P values between 0.04 and 0.06. DESIGN: Cross sectional study of all 260 abstracts in PubMed of articles published in 2003 that contained "relative risk" or "odds ratio" and reported results from a randomised trial, and random samples of 130 abstracts from cohort studies and 130 from case-control studies. P values were noted or calculated if unreported. MAIN OUTCOME MEASURES: Prevalence of significant P values in abstracts and distribution of P values between 0.04 and 0.06. RESULTS: The first result in the abstract was statistically significant in 70% of the trials, 84% of cohort studies, and 84% of case-control studies. Although many of these results were derived from subgroup or secondary analyses, or biased selection of results, they were presented without reservations in 98% of the trials. P values were more extreme in observational studies (P < 0.001) and in cohort studies than in case-control studies (P = 0.04). The distribution of P values around P = 0.05 was extremely skewed. Only five trials had 0.05 < or = P < 0.06, whereas 29 trials had 0.04 < or = P < 0.05. I could check the calculations for 27 of these trials. One of four non-significant results was significant. Four of the 23 significant results were wrong, five were doubtful, and four could be discussed. Nine cohort studies and eight case-control studies reported P values between 0.04 and 0.06, but in all 17 cases P < 0.05. Because the analyses had been adjusted for confounders, these results could not be checked. CONCLUSIONS: Significant results in abstracts are common but should generally be disbelieved.

Abstracting and Indexing↗
PubMed2006

[Constraints on publication rights in industry-initiated clinical trials--secondary publication].

In 22 of 44 industry-initiated clinical trial protocols from 1994-95, it was noted that the sponsor either owned the data or needed to approve the manuscript; another 18 protocols had other constraints. Furthermore, in 16 trials, the sponsor had access to accumulating data, and in an additional 16 trials the sponsor could stop the trial at any time, for any reason. These facts were not noted in any of the trial reports. We found similar constraints on publication rights in 44 protocols from 2004. This tight sponsor control over industry-initiated trials should be changed.

Clinical Trials Data Monitoring Committees↗
PubMed2006

[COX-2 inhibitors and other non-steroidal anti-inflammatory agents--what is their future?].

The story of the development, approval, marketing and use of COX-2 inhibitors is one of failures at all levels. Publications in top medical journals essential for marketing were seriously flawed; many cases of thromboses in trials with rofecoxib were not revealed; trials were not representative for the population of patients; the U.S. FDA did not require the relevant trials; and the marketing was extremely aggressive and misleading. These drugs have likely caused the deaths of thousands of patients. The use of all NSAIDs should be restricted as much as possible. Drug trials should be a public enterprise.

Advertising↗
PubMed2006

[Are invitations to mammography screening a reasonable basis for informed consent?-- Secondary publication].

There is a delicate balance between the benefits and harms of mammography screening, and women should decide for themselves, on an informed basis. The invitation to have a mammography is the only source of information provided to all eligible women, and we explored whether it provides such a basis. We collected invitations from English-speaking and Scandinavian countries. The major benefit of screening, a reduction in breast cancer mortality, was mentioned in 30 of 31 invitations, whereas the most important harms, overdiagnosis and overtreatment, were not mentioned in any of the invitations.

Comment↗