Showing papers by "Peter C Gøtzsche published in 2011"
TL;DR: The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate.
Abstract: Flaws in the design, conduct, analysis, and reporting of randomised trials can cause the effect of an intervention to be underestimated or overestimated. The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate
22,227 citations
TL;DR: One-third of Cochrane reviews with substantial heterogeneity had major problems in relation to their handling of heterogeneity, and more attention is needed to this issue, as the problems identified can be essential for the conclusions of the reviews.
Abstract: Dealing with heterogeneity in meta-analyses is often tricky, and there is only limited advice for authors on what to do. We investigated how authors addressed different degrees of heterogeneity, in particular whether they used a fixed effect model, which assumes that all the included studies are estimating the same true effect, or a random effects model where this is not assumed. We sampled randomly 60 Cochrane reviews from 2008, which presented a result in its first meta-analysis with substantial heterogeneity (I2 greater than 50%, i.e. more than 50% of the variation is due to heterogeneity rather than chance). We extracted information on choice of statistical model, how the authors had handled the heterogeneity, and assessed the methodological quality of the reviews in relation to this. The distribution of heterogeneity was rather uniform in the whole I2 interval, 50-100%. A fixed effect model was used in 33 reviews (55%), but there was no correlation between I2 and choice of model (P = 0.79). We considered that 20 reviews (33%), 16 of which had used a fixed effect model, had major problems. The most common problems were: use of a fixed effect model and lack of rationale for choice of that model, lack of comment on even severe heterogeneity and of reservations and explanations of its likely causes. The problematic reviews had significantly fewer included trials than other reviews (4.3 vs. 8.0, P = 0.024). The problems became less pronounced with time, as those reviews that were most recently updated more often used a random effects model. One-third of Cochrane reviews with substantial heterogeneity had major problems in relation to their handling of heterogeneity. More attention is needed to this issue, as the problems we identified can be essential for the conclusions of the reviews.
130 citations
TL;DR: It is argued that the distinction between publicly-funded and industry-funded research is an artificial and irrelevant one, as the interests of the patients must override commercial interests, and why it is a moral imperative to render all results from all trials involving humans, also healthy volunteers, publicly available.
Abstract: International calls for registering all trials involving humans and for sharing the results, and sometimes also the raw data and the trial protocols, have increased in recent years. Such calls have come, for example, from the Organization for Economic Cooperation and Development (OECD), the World Health Organization (WHO), the US National Institutes of Heath, the US Congress, the European Commission, the European ombudsman, journal editors, The Cochrane Collaboration, and several funders, for example the UK Medical Research Council, the Wellcome Trust, the Bill and Melinda Gates Foundation and the Hewlett Foundation.
129 citations
TL;DR: The time has come to reassess whether universal mammographic screening should be recommended for any age group because the declines in breast cancer mortality can be ascribed mainly to improved treatments and breast cancer awareness.
Abstract: The time has come to reassess whether universal mammographic screening should be recommended for any age group because the declines in breast cancer mortality can be ascribed mainly to improved treatments and breast cancer awareness; currently, we see that screening has only a minor effect on mortality (if any).
122 citations
TL;DR: Peter Gøtzsche and Anders Jørgensen describe their efforts to get access to unpublished trial reports from the European Medicines Agency.
Abstract: Widespread selective reporting of research results means we don’t know the true benefits and harms of prescribed drugs. Peter Gotzsche and Anders Jorgensen describe their efforts to get access to unpublished trial reports from the European Medicines Agency
119 citations
TL;DR: It is believed that many invasive breast cancers detected by repeated mammography screening do not persist to be detected by screening at the end of 6 years, suggesting that the natural course of many of the screen-detected invasive breast cancer is to spontaneously regress.
Abstract: Summary Background The natural history of screen-detected breast cancers is not well understood. A previous analysis of the incidence change during the introduction of the Norwegian screening programme in the late 1990s suggested that the natural history of many screen-detected invasive breast cancers is to regress spontaneously but the study was possibly confounded by use of hormone replacement therapy in the population. We did a similar analysis of data collected during an earlier period when few women were exposed to hormone replacement therapy. Methods We compared cumulative breast cancer incidence in age-matched cohorts of women living in seven Swedish counties before and after the initiation of public mammography screening between 1986 and 1990. Women aged 40–49 years were invited to screening every year and women aged 50–74 years were invited every 2 years. A screened group including all women aged 40–69 years (n=328 927) was followed-up for 6 years after the first invitation to the programme. A control group including all women in the same age range (n=317 404) was also followed-up for 6 years—4 years without screening and 2 years when they entered the screening programme. Screening attendance was much the same in both groups (close to 80%). Counts of incident invasive breast cancers were obtained from the Swedish Cancer Registry (in-situ cancers were excluded). Findings Before the age-matched controls were invited to be screened at the end of their follow-up period, the 4-year cumulative incidence of invasive breast cancer was significantly higher in the screened group (982 per 100 000) than it was in the control group (658 per 100 000) (relative risk [RR] 1·49, 95% CI 1·41–1·58). Even after prevalence screening in the control group, the screened group had higher 6-year cumulative incidence of invasive breast cancer (1443 per 100 000 vs 1269 per 100 000; RR 1·14, 1·10–1·18). Interpretation Because the cumulative incidence among controls did not reach that of the screened group, we believe that many invasive breast cancers detected by repeated mammography screening do not persist to be detected by screening at the end of 6 years, suggesting that the natural course of many of the screen-detected invasive breast cancers is to spontaneously regress. Funding None.
89 citations
TL;DR: Mammography screening in Norway was associated with a noticeable increase in rates for breast cancer surgery in women aged 50-69 (the age group invited to screening) and also an increase in mastectomy rates.
Abstract: Objective To determine the effect of mammography screening on surgical treatment for breast cancer. Design Comparative analysis of data from Norwegian cancer registry. Setting Mammography screening, Norway (screening of women aged
53 citations
TL;DR: It is concluded that spokespeople for the NHS Breast Screening Programme have stuck to the beliefs about benefit that prevailed 25 years ago and official documents still downplay this most important harm of breast cancer screening.
Abstract: The information provided to the public by the NHS Breast Screening Programme has been criticized for lack of balance, omission of information on harms and substantially exaggerated estimates of benefit. These shortcomings have been particularly evident in the various invitation leaflets for breast screening and in the Programme's own 2008 Annual Review, which celebrated 20 years of screening. The debate on screening has been heated after new data published in the last two years questioned the benefit and documented substantial harm. We therefore analysed whether the recent debate and new pivotal data about breast screening has had any impact on the contents of the new 2010 leaflet and on the 2010 Annual Review. We conclude that spokespeople for the Programme have stuck to the beliefs about benefit that prevailed 25 years ago. Concerns about over-diagnosis have not been addressed either and official documents still downplay this most important harm of breast cancer screening.
46 citations
TL;DR: Multiplicity of data can affect the findings of systematic reviews and meta-analyses and should comply with prespecified protocols that clearly identify time points, intervention groups, and scales of interest.
Abstract: Objectives To examine the extent of multiplicity of data in trial reports and to assess the impact of multiplicity on meta-analysis results.
Design Empirical study on a cohort of Cochrane systematic reviews.
Data sources All Cochrane systematic reviews published from issue 3 in 2006 to issue 2 in 2007 that presented a result as a standardised mean difference (SMD). We retrieved trial reports contributing to the first SMD result in each review, and downloaded review protocols. We used these SMDs to identify a specific outcome for each meta-analysis from its protocol.
Review methods Reviews were eligible if SMD results were based on two to ten randomised trials and if protocols described the outcome. We excluded reviews if they only presented results of subgroup analyses. Based on review protocols and index outcomes, two observers independently extracted the data necessary to calculate SMDs from the original trial reports for any intervention group, time point, or outcome measure compatible with the protocol. From the extracted data, we used Monte Carlo simulations to calculate all possible SMDs for every meta-analysis.
Results We identified 19 eligible meta-analyses (including 83 trials). Published review protocols often lacked information about which data to choose. Twenty-four (29%) trials reported data for multiple intervention groups, 30 (36%) reported data for multiple time points, and 29 (35%) reported the index outcome measured on multiple scales. In 18 meta-analyses, we found multiplicity of data in at least one trial report; the median difference between the smallest and largest SMD results within a meta-analysis was 0.40 standard deviation units (range 0.04 to 0.91).
Conclusions Multiplicity of data can affect the findings of systematic reviews and meta-analyses. To reduce the risk of bias, reviews and meta-analyses should comply with prespecified protocols that clearly identify time points, intervention groups, and scales of interest.
44 citations
TL;DR: The Canadian Task Force on Preventive Health Care should be congratulated for its new recommendations on screening for breast cancer in women at this time of year.
Abstract: See related guidelines by the Canadian Task Force on Preventive Health Care on page [1991][1] and at [www.cmaj.ca/lookup/doi/10.1503/cmaj.110334][2]
The Canadian Task Force on Preventive Health Care should be congratulated for its new recommendations on screening for breast cancer in women at
43 citations
TL;DR: Niels Ryberg Finsen was awarded the Nobel Prize in 1903 for his contribution to the treatment of diseases, especially lupus vulgaris, with concentrated light radiation, whereby he has opened a new avenue for medical science.
Abstract: Niels Ryberg Finsen was born 1860 in Thorshavn, Faroe Islands, and died in 1904. He was awarded the Nobel Prize in 1903 ‘in recognition of his contribution to the treatment of diseases, especially lupus vulgaris, with concentrated light radiation, whereby he has opened a new avenue for medical science’.
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TL;DR: A systematic review of the mammography screening trials using metaregression uncovered bias in both assessment of the cause of death and of the number of cancers in advanced stages, which cannot be explained by differences in screening effectiveness.
Abstract: The mammography screening trials have shown varying results. This could be because screening was better in some trials than in others at advancing the time of diagnosis. If so, more cancers would be identified in such trials relative to the control group, and fewer of the cancers would have reached an advanced stage. I performed a systematic review of the mammography screening trials using metaregression. Finding many cancers was not related to the size of the reduction in breast cancer mortality (p = 0.19 after seven and p = 0.73 after 13 years of follow-up). In contrast, finding few cancers in stage II and above predicted a larger reduction in breast cancer mortality (p = 0.04 and p = 0.006). This expected association was also found for node-positive cancers (p = 0.008 and p = 0.04). However, a screening effectiveness of zero (same proportion of node-positive cancers in the screened group as in the control group) predicted a significant 16% reduction in breast cancer mortality after 13 years (95% confidence interval, 9% to 23% reduction). This can only occur if there is bias. Further analyses uncovered bias in both assessment of the cause of death and of the number of cancers in advanced stages. Consequently, the differences in the reported reductions in breast cancer mortality cannot be explained by differences in screening effectiveness. Given that the size of the bias was similar to the estimated screening effect, screening appeared ineffective.
TL;DR: To compare the sales of benzodiazepines and SSRIs within the primary care sector in Denmark and relate changes in usage to number of indications and products on the market, the sales curves of psychotropic drugs in the period 1970 to 2007 are established.
Abstract: Background: Prescribing of selective serotonin reuptake inhibitors (SSRIs) has increased dramatically. Objective: To compare the sales of benzodiazepines and SSRIs within the primary care sector in Denmark and relate changes in usage to number of indications and products on the market. Methods: We used data from various sources to establish the sales curves of psychotropic drugs in the period 1970 to 2007, based on the Anatomic Therapeutic Classification system and Defined Daily Doses. Results: Fluctuations in sales of psychotropic drugs that cannot be explained by disease prevalence were caused by changes in sales of the benzodiazepines and SSRIs. We found a decline in the sales of benzodiazepines after a peak in 1986, likely due to the recognition that they cause dependence. From a low level in 1992, we found that the sales of SSRIs increased almost linearly by a factor of 18, up to 44 DDD per 1000 inhabitants, which was closely related to the number of products on the market that increased by a factor of 16. Conclusions: Sales of antidepressant drugs are mainly determined by market availability of products indicating that marketing pressures are playing an important role. Thus the current level of use of SSRIs may not be evidence-based, which is supported by studies showing that the effect of SSRIs has been overestimated.
TL;DR: This is the protocol for a review and the objectives are to quantify the benefits and harms of health checks and to establish a baseline for assessing the risks and benefits of these checks.
Abstract: This is the protocol for a review and there is no abstract. The objectives are as follows:
To quantify the benefits and harms of health checks.
01 Jan 2011
TL;DR: The form for videnskabelig uredelighed er udbredt (26-28), fordi idéen netop er at holde den skjult as discussed by the authors.
Abstract: Der er penge i laegemidler. Så mange, at det naermest er umuligt at straffe medicinalfirmaers ulovligheder økonomisk. KRONIK: De seneste år har budt på en raekke skandaler i medicinalindustrien. Firmaers hemmeligholdelse af forskningsdata og laegers interessekonflikter er med til at sløre sandhederne om praeparaternes virkninger. Denne form for videnskabelig uredelighed er udbredt (26-28), men kommer i reglen ikke frem, fordi idéen netop er at holde den skjult.
TL;DR: Access to clinical study reports and trial protocols of placebo controlled trials at the European Medicines Agency is gained.
Abstract: Jorgensen and I recently gained access to clinical study reports and trial protocols of placebo controlled trials at the European Medicines Agency (EMA).1 Some drugs, however, have not been approved centrally, and in such cases the EMA advises contacting the relevant national drug agencies.
For the antidepressant drug fluoxetine, the United Kingdom acts as Reference Member State according to the Mutual Recognition …
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TL;DR: They selected a group of women screened between 2003 and 2007, who were at increased risk of dying from breast cancer because of their family history, and compared them with another group at increasedrisk, selected from the unscreened group in the UK Age Trial during 1991–99, using tumour characteristics to predict 10-year survival.
Abstract: 1basic premises of cancer screening research are disregarded. They selected a group of women screened between 2003 and 2007, who were at increased risk of dying from breast cancer because of their family history, and compared them with another group at increased risk, selected from the unscreened group in the UK Age Trial during 1991–99. They used tumour characteristics to predict 10-year survival (which they converted to 10-year mortality). The compared groups diff er greatly, and how Duff y and co-workers tried to make them comparable is unclear. Some of the detailed inclusion and exclusion criteria that applied to the screened group, such as family history, were largely unavailable for the UK Age Trial, the age-groups studied diff ered, and the women were screened for only 4 years, whereas the cancers in the UK Age Trial were identifi ed over 8 years. Duff y and co-workers conceal
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TL;DR: Mike Richards and Harpal Kumar, chief executive at Cancer Research UK, were put in charge of the review but neither is independent, and this is reflected in the references he chose for his letter.
Abstract: Mike Richards and Harpal Kumar, chief executive at Cancer Research UK, were put in charge of the review but neither is independent.
For Richards, this is reflected in the references he chose for his letter.1 The first is used to support his claim of a 35% effect of breast screening in attenders, although they are healthier than non-attenders. The estimate is therefore misleading.
The second …
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