Peter C Gøtzsche’s research while affiliated with Rigshospitalet and other places
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Our analysis suggests that well-monitored warfarin might be equally good, or even better, for atrial fibrillation depending on the DOAC and outcome. Our analysis warrants granular investigations based on the COMBINE AF (A Collaboration between Multiple institutions to Better Investigate Non-vitamin K antagonist oral anticoagulant use in Atrial Fibrillation) data set to establish which anticoagulant to use and in which setting. New analyses should be conducted with predefined TTR thresholds and transparently reported.
Background
A variety of estimates of the benefits and harms of mammographic screening for breast cancer have been
published and national policies vary. This is an update of a review previously updated 2013 and originally
published 2001.
Objectives
To assess the effect of screening for breast cancer with mammography on mortality and morbidity.
Search methods
For this 2023 update, we searched PubMed, CENTRAL, the Cochrane Breast Cancer Group Specialised
Register, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and
ClinicalTrials.gov up to 28 February 2023.
Selection criteria
Randomised clinical trials (RCTs) comparing mammographic screening with no mammographic screening.
Data collection and analysis
Two authors independently extracted data. Study authors were contacted for additional information. Our main
outcomes of interest were deaths due to breast cancer, any cancer, and due to any cause, and harms measured
as overdiagnosis, number of mastectomies, lumpectomies, use of radiotherapy and of chemotherapy. Certainty
of evidence was assessed with GRADE.
Main results
Eight eligible trials from Europe and North America that compared women offered screening mammography with
women not offered screening were included. We excluded a trial because the randomisation failed to produce
comparable groups. The eligible trials included 600,000 women in the age range 39 to 74 years.
The trials with adequate randomisation did not show a benefit in terms of a reduction in breast cancer mortality at
13 years (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.79 to 1.02; 33 vs 30 deaths from breast cancer per
10,000 women; 3 RCTs; 292,153 participants). The findings at 24 years were similar to those at 13 years. Our
certainty in both estimates was downgraded 1 level to 'low' due to changes in technology and treatment
(indirectness) and due to imprecision. The trials with suboptimal randomisation showed a reduction in breast
cancer mortality at 13 years with an RR of 0.75 (95% CI 0.67 to 0.83; 4 RCTs; 306,937 participants; very low
certainty evidence).
In women below age 50 years, the results from adequately randomised trials did not show a reduction in breast
cancer mortality at 13 years of follow-up (RR 0.87, CI 0.73 to 1.03; 28 vs 24 deaths from breast cancer per 10,000
women; 3 RCTs; 218,697 participants, low certainty evidence), nor for women at least 50 years (RR 0.94, CI 0.77
to 1.15; 53 vs 50 deaths from breast cancer per 10,000 women; 2 RCTs; 74,261 participants, low certainty
evidence). Only one trial included women aged 70 years and above and could not provide a reliable effect
estimate.We found that breast cancer mortality was an unreliable outcome that was biased in favour of screening, mainly
because of the risk of differential misclassification of cause of death. The trials with adequate randomisation did
not find an effect of screening on total cancer mortality, including breast cancer, (RR 1.00, 95% CI 0.96 to 1.04;
288 vs 288 cancer deaths per 10,000 women; 3 RCTs; 292,954 participants; moderate certainty evidence; the
follow-up was 10.5 years for Canada, 9 years for Malmo and 23 years for the UK age trial). All-cause mortality
was not reduced (RR 0.98, 95% CI 0.94 to 1.03 after 7 years; RR 0.99, 95% CI 0.95 to 1.03 after 13 years; 324 vs
328 deaths per 10,000 women; and RR 1.01, 95% CI 0.99 to 1.04 after 24 years; 773 vs 765 deaths per 10,000
women; 2 RCTs; 250,671 participants; moderate certainty evidence) in the adequately randomised trials.
There were more lumpectomies and mastectomies combined in the screened groups, likely reflecting
overtreatment (RR 1.31, 95% CI 1.22 to 1.42; 164 vs 214 operations per 10,000 women; 2 RCTs; 132,321
participants; moderate certainty evidence), as were the number of mastectomies alone (RR 1.20, 95% CI 1.08 to
1.32; 122 vs 102 per 10,000 women; 2 RCTs; 132,321; moderate certainty evidence). The use of radiotherapy
was similarly increased whereas there was no difference in the use of chemotherapy (data for each outcome
available from only one adequately randomised trial; low certainty evidence). Breast screening increased the
number of breast cancer diagnoses (overdiagnosis)(RR 1.25, CI 1.18 to 1.34, 142 vs 113 diagnoses at 7 to 9
years of follow-up; 3 RCTs, 292,979 participants; moderate certainty evidence) in trials that did not screen the
control group after the intervention phase.
Authors' conclusions
Because of substantial changes in screening technology, treatment, and breast cancer awareness since the
trials were done, the estimates from the trials are uncertain in today's setting. As breast cancer mortality is an
unreliable outcome that is biased in favour of screening, it is noteworthy that screening did not reduce total
cancer mortality or total mortality. Breast screening does not meet the criteria that population screening should be
based on rigorously performed randomised trials that show that the benefits outweigh the harms. No studies
have been completed in low income countries and one small study from Colombia has yet to provide data on long
term outcomes. Women, clinicians and policy makers should consider the trade-offs and the uncertainties
carefully when they decide whether or not to attend or support breast screening programmes.
Aims
We have previously described the European Medicines Agency’s (EMA) and the US Food and Drug Administration’s guidelines, each for a specific psychiatric indication, on how to design pivotal drug trials used in new drug applications. Here, we report on our efforts over 3 years to retrieve conflicts of interest declarations from EMA. We wanted to assess potential internal industry influence judged as the proportion of guideline committee members with industry conflicts of interest.
Methods
We submitted Freedom of Information requests in February 2020 to access EMA’s lists of committee members (and their declared conflicts of interest) involved in drafting the 13 ‘Clinical efficacy and safety’ guidelines available on EMA’s website pertaining to psychiatric indications. In our request, we did not specify the exact EMA committees. Here, we describe the received documents and report the proportion of members with industry interests (i.e. defined as any financial industry relationship). It is a follow-up paper to our first report ( http://doi.org/10.1017/S2045796021000147 ).
Results
After 2 years and 9 months (November 2022), the EMA sent us member lists and corresponding conflicts of interest declarations from the Committee for Medicinal Products for Human use (CHMP) from 2012, 2013 and 2017. These member lists pertained to 3 of the 13 requested guidelines (schizophrenia, depression and autism spectrum disorder). The 10 remaining guidelines were published before 2011 and EMA stated that they needed to require permission from their expert members (with unknown retrieval rate) and foresaw excessive workload and long wait. Therefore, we withdrew our request. The CHMPs from 2012, 2013 and 2017 had from 34 to 36 members; 39%–44% declared any interests and we judged 14%–18% as having industry interests. For the schizophrenia guideline, we identified two members with industry interests to companies who submitted feedback on the guideline. We did not receive declarations from the Central Nervous System (CNS) Working Party, the CHMP appointed expert group responsible for drafting and incorporating feedback into the guidelines.
Conclusions
After almost 3 years, we received information, which only partly addressed our request. We recommend EMA to improve transparency by publishing the author names and their corresponding conflicts of interest declarations directly in the ‘Clinical efficacy and safety’ guidelines and to not remove conflicts of interest declarations after 1 year from their website to reduce the risk of stealth corporate influence during the development of these influential guidelines.
Background:
Depression drugs can be difficult to come off due to withdrawal symptoms. Gradual tapering with tapering support is needed to help patients withdraw safely.
Objective:
To review the withdrawal success rates, using any intervention, and the effects on relapse/recurrence rates, symptom severity, quality of life, and withdrawal symptoms.
Methods:
Systematic review based on PubMed and Embase searches (last search 4 October 2022) of randomised trials with one or more treatment arms aimed at helping patients withdraw from a depression drug, regardless of indication for treatment. We calculated the mean and median success rates and the risk difference of depressive relapse when discontinuing or continuing depression drugs.
Results:
We included 13 studies (2085 participants). Three compared two withdrawal interventions and ten compared drug discontinuation vs. continuation. The success rates varied hugely between the trials (9% to 80%), with a weighted mean of 47% (95% confidence interval 38% to 57%) and a median of 50% (interquartile range 29% to 65%). A meta-regression showed that the length of taper was highly predictive for the risk of relapse (P = 0.00001). All the studies we reviewed confounded withdrawal symptoms with relapse; did not use hyperbolic tapering; withdrew the depression drug too fast in a linear fashion; and stopped it entirely when receptor occupancy was still high.
Conclusion:
The true proportion of patients on depression drugs who can stop safely without relapse is likely considerably higher than the 50% we found.
We believe that the NHS has a clinical and moral obligation to help those who have been harmed by taking their medication as prescribed. Panorama has revealed the scale of the problem and the horrendous impact it has had on so many people’s lives. To help mitigate these impacts, we therefore urgently call upon the UK government to fund and implement withdrawal support services, including a national helpline.
The current paradigm in psychiatry is that psychosis should be treated with neuroleptics as first-line therapy. Neuroleptics should not be used at all. Randomised trials have shown that they kill many patients and do not have clinically relevant effects but cause permanent brain damage in most patients treated long-term and prevent them from coming back to a more normal life. If an acutely disturbed patient feels that a drug is needed, benzodiazepines work faster than neuroleptics, are much less toxic, and are also what virtually all patients prefer if asked. Psychiatry seems to be the only area in society where the law is systematically being violated all over the world. We need to respect the patients’ rights and the law, which will also lead to better outcomes.KeywordsPsychosisPsychiatryPsychiatric drugs
Randomized controlled trials remain the reference standard for healthcare research on effects of interventions, and the need to report both benefits and harms is essential. The Consolidated Standards of Reporting Trials (the main CONSORT) statement includes one item on reporting harms (i.e., all important harms or unintended effects in each group). In 2004, the CONSORT group developed the CONSORT Harms extension; however, it has not been consistently applied and needs to be updated. Here, we describe CONSORT Harms 2022, which replaces the CONSORT Harms 2004 checklist, and shows how CONSORT Harms 2022 items could be incorporated into the main CONSORT checklist. Thirteen items from the main CONSORT were modified to improve harms reporting. Three new items were added. In this article, we describe CONSORT Harms 2022 and how it was integrated into the main CONSORT checklist and elaborate on each item relevant to complete reporting of harms in randomized controlled trials. Until future work from the CONSORT group produces an updated checklist, authors, journal reviewers, and editors of randomized controlled trials should use the integrated checklist presented in this paper.
Citations (46)
... We open this issue of IJRSM with the systematic review entitled "Interventions to help patients withdraw from depression drugs: A systematic review" from the Institute for Scientific Freedom, Denmark [1]. Similar to the last issue, we emphasize the detrimental effects of antidepressant use on mental health and quality of life and thereby bridge these two IJRSM issues. ...
... • Addition of items related to reporting of how harms 24 were assessed and analyzed (items 7, 15, 21a, 23a, 27), how outcomes 25 were measured and analyzed (items 14,26), and how the intervention 27,28 and comparator were actually administered and by whom (item 24). ...
... 22 The trial was conducted in accordance with The Declaration of Helsinki, ICH-GCP, local and national regulations and is reported according to Consolidated Standards of Reporting Trials (CONSORT) Harms 2022 guidelines. 23 The trial was monitored by an independent monitoring organisation, Karolinska Trial Alliance (KTA), before, during and after the trial according to the monitoring plan. An independent data safety monitoring board (DSMB) reviewed the data three times during the trial. ...
... Mental and medical health practices consistently fall short for patients diagnosed with schizophrenia spectrum conditions. Treatment plans are predominantly stereotyped, heavily reliant on second-generation antipsychotics [1][2][3][4], and rarely include validated psychosocial or psychotherapeutic interventions [5][6][7], Verdoux et al., 2010). This pattern persists despite widespread agreement on heterogenous presentation and treatment outcome [3,[8][9][10][11], moreover, a tremendous amount of the variability in prognosis, etiology, and even the effectiveness of pharmacotherapy is accounted for by factors overlooked in diagnosis and/or outcomes monitoring [10,[12][13][14]. ...
... Cases of liver damage (hepatotoxicity) were reported following vaccination against COVID-19 [24]. Another study found that adenovirus-based vaccines were associated with increased risk of blood clots (thrombosis) and low platelet levels (thrombocytopenia), while mRNA vaccines were linked to a higher risk of heart inflammation (myocarditis), with a fatality rate of 1-2 per 200 cases [25]. There is also evidence of how vaccines can trigger immune reactions leading to serious neurological harm [25]. ...
... This observational cross-sectional study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) 29 guidelines was conducted from March 1, 2024, to June 10, 2024, at the Fibromyalgia and Chronic Fatigue Syndrome Association of Tenerife, located in San Cristóbal de La Laguna, Spain. The study protocol was approved by the institutional review board of the ethics committee of Complejo Hospitalario Universitario de Canarias (Canary Islands, Spain) (approval no. ...
... Sin embargo, algunos pacientes tratados han informado que presentaron los efectos adversos de pensamientos y comportamientos suicidas y homicidas, algunos han referido presentar sueños en los que mataban a personas de una forma sangrienta. Estos efectos adversos ya se han descrito desde antes de la pandemia del COVID que se pueden presentar en los pacientes que reciben ISRS como tratamiento de la depresión, reportándose que se presentan con mayor frecuencia en los adolescentes y adultos menores de 24 años y después de las 3 semanas de su uso diario [5][6][7][8][9][10][11][12][13][14][15]. En el caso del Long COVID o COVID Persistente, estos efectos adversos también se han presentado en pacientes mayores de 24 años luego de tomar Fluvoxamina durante más de 4 semanas. ...
... Anonymous or pseudonymous whistleblowing is frequently employed to report misconduct in the healthcare or pharmaceutical industries, but these may be presented with a higher proportion of suspicion over factual evidence. While some are supportive of the anonymity in terms of protection of whistleblowers and the projected consequential benefits of avoiding harm (Gøtzsche, 2022), others may dismiss such acts as being akin to hearsay (Healy, 2022). The specificity and clarity in terms of factual evidence in IME-PPPRs would allow the audience to examine and verify the issue or concern for itself, without being unduly distracted by an upfront allegation of misconduct. ...
... Данная проблема приобретает особую акту-альность в современном обществе в связи с ускорением темпа жизни. Процесс информатизации и компьютеризации непрерывно увеличивают число событий за единицу времени в повседневной жизни человека [46]. С ростом числа происходящих событий интенсифицируется поток сообщений о них, который воспринимается и перерабатывается сознанием человека с возрастающим напряжением. ...
... In the context of VVG research, such biases may manifest as a preference for evidence that aligns with one's own prior findings or theoretical perspectives. Researchers might apply more stringent critiques to studies that contradict their conclusions (de Vrieze, 2018) or overlook conflicting evidence through practices like selective citing (Gøtzsche, 2022;Nagy, 2024). Future research should investigate the presence and impact of such biases among VVG researchers to better understand their role in the ongoing lack of consensus and to identify strategies for fostering greater objectivity and cohesion in the field. ...