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Peter C Gøtzsche

Publications and source records attributed to Peter C Gøtzsche.

At least 37 records · Page 2Linked to original sources
PubMed2006

Flaws in design, analysis and interpretation of Pfizer's antifungal trials of voriconazole and uncritical subsequent quotations.

We have previously described how a series of trials sponsored by Pfizer of its antifungal drug, fluconazole, in cancer patients with neutropenia handicapped the control drug, amphotericin B, by flaws in design and analysis. We describe similar problems in two pivotal trials of Pfizer's new antifungal agent, voriconazole, published in a prestigious journal. In a non-inferiority trial, voriconazole was significantly inferior to liposomal amphothericin B, but the authors concluded that voriconazole was a suitable alternative. The second trial used amphothericin B deoxycholate as comparator, but handicapped the drug by not requiring pre-medication to reduce infusion-related toxicity or substitution with electrolytes and fluid to reduce nephrotoxicity, although the planned duration of treatment was 84 days. Voriconazole was given for 77 days on average, but the comparator for only 10 days, which precludes a meaningful comparison. In a random sample of 50 references to these trials, we found that the unwarranted conclusions were mostly uncritically propagated. It was particularly surprising that relevant criticism raised by the FDA related to the first trial was only quoted once, and that none of the articles noted the obvious flaws in the design of the second trial. We suggest that editors ensure that the abstract reflects fairly on the remainder of the paper, and that journals do not impose any time limit for accepting letters that point out serious weaknesses in a study that have not been noted before.

Journal Article↗
PubMed2006

Results of the Two-County trial of mammography screening are not compatible with contemporaneous official Swedish breast cancer statistics.

BACKGROUND: National mammography screening programmes are based on the results of randomised trials, but the quality of these trials has recently been questioned. The Swedish Two-County trial reported a 31% reduction in breast cancer mortality and was instrumental for the introduction of screening in many countries. In this trial, official Swedish health registries were used to identify breast cancers and breast cancer deaths in the study population. METHODS: We used data from the same registries to estimate the numbers of breast cancer cases and breast cancer deaths among the included women. RESULTS: Compared to official Swedish statistics we found that 192 breast cancer cases and 43 breast cancer deaths seem to be missing in the main publication of the Two-County trial; we found similar discrepancies in two updates of the trial. These large differences can hardly be explained by random fluctuations in the cancer occurrence. CONCLUSION: The data reported for the Two-County trial are incomplete. Other data indicate that the mortality results in a recent report were flawed.

Bias↗
PubMed2005

[Selective reporting of positive outcomes in randomised trials--secondary publication.. A comparison of protocols with published reports].

INTRODUCTION: Selective reporting of positive outcomes is associated with bias. MATERIALS AND METHODS: We conducted a cohort study of 102 protocols of randomised trials approved by the Scientific Ethics Committees for Copenhagen and Frederiksberg in 1994-1995 and the corresponding 122 reports. RESULTS: The median proportion of incompletely reported outcomes per trial was 50%. Statistically significant outcomes were more often fully reported, odds ratio 2.4. In 62% of trials, at least one primary outcome was changed. DISCUSSION: Outcomes in randomised trials are often reported selectively.

Clinical Protocols↗
PubMed2005

Comparison of descriptions of allocation concealment in trial protocols and the published reports: cohort study.

OBJECTIVES: To compare how allocation concealment is described in publications of randomised clinical trials and corresponding protocols, and to estimate how often trial publications with unclear allocation concealment have adequate concealment according to the protocol. DESIGN: Cohort study of 102 sets of trial protocols and corresponding publications. SETTING: Protocols of randomised trials approved by the scientific and ethical committees for Copenhagen and Frederiksberg, 1994 and 1995. MAIN OUTCOME MEASURES: Frequency of adequate, unclear, and inadequate allocation concealment and sequence generation in trial publications compared with protocols, and the proportion of protocols where methods were reported to be adequate but descriptions were unclear in the trial publications. RESULTS: 96 of the 102 trials had unclear allocation concealment according to the trial publication. According to the protocols, 15 of these 96 trials had adequate allocation concealment (16%, 95% confidence interval 9% to 24%), 80 had unclear concealment (83%, 74% to 90%), and one had inadequate concealment. When retrospectively defined loose criteria for concealment were applied, 83 of the 102 trial publications had unclear concealment. According to their protocol, 33 of these 83 trials had adequate allocation concealment (40%, 29% to 51%), 49 had unclear concealment (59%, 48% to 70%), and one had inadequate concealment. CONCLUSIONS: Most randomised clinical trials have unclear allocation concealment on the basis of the trial publication alone. Most of these trials also have unclear allocation concealment according to their protocol.

Cohort Studies↗