Showing papers by "Peter C Gøtzsche published in 2019"

Clinical guidelines on antidepressant withdrawal urgently need updating

Abstract: In February 2018 the international debate on antidepressant withdrawal was reignited. In response to a letter published in The Times by Davies et al. on the benefits and harms of antidepressants, the Royal College of Psychiatrists publicly stated that ‘[for] the vast majority of patients any unpleasant symptoms experienced on discontinuing antidepressants have resolved within two weeks of stopping treatment’.

Effect of lithium on suicide and mortality in mood disorders: A systematic review

Abstract: Objective To assess if lithium treatment in patients with mood disorders, for instance depression, bipolar disorders, and schizoaffective disorders, has an effect on total mortality and suicide. Design Systematic review and meta-analysis. Main outcome measure Total mortality. Secondary outcome was suicide. Data sources PubMed and ClinicalTrials.gov. Eligible trials were randomized double-blind trials comparing lithium with placebo in patients with mood disorders who were not already on lithium before randomization in order to avoid withdrawal effects in the placebo group. Data extraction and analysis Two researchers extracted data independently. Data were analysed with Review Manager 5.3 (Peto odds ratio). Results We found 45 eligible studies. Only four studies reported any suicides or other deaths in the lithium or placebo group. There was a significant reduction in total mortality (two versus nine), odds ratio 0.28 (95% confidence interval 0.08 to 0.93). There was no statistically significant reduction in suicides, (none versus three), odds ratio 0.13 (0.01 to 1.27). Conclusion According to our study, lithium reduces total mortality in mood disorders but not suicide. Because of small numbers and unreliable data, the findings should be interpreted with caution.

Do protocols for new randomised trials take previous similar trials into account? Cohort study of contemporary trial protocols.

Abstract: Objective To investigate to what extent evidence from previous similar trials or systematic reviews was considered before conducting new trials. Design Cohort study of contemporary protocols for trials with ethical approval. Methods All protocols for randomised trials approved by the five ethical committees in Denmark between January 2012 and March 2013 were screened for eligibility. Included protocols were read in full to determine whether a systematic search had been conducted and references were checked to evaluate whether trial rationale and design could be challenged for not adequately considering previous evidence. To investigate whether protocols cited relevant trials, we used simple search strategies that could easily be conducted by researchers without experience with literature searches. Results Sixty-seven protocols were included. Only two (3%) of the protocols explicitly stated to have conducted a literature search and only one (1%) provided information that allowed the search to be replicated. Eleven (16%) of the protocols described trials where we found the information insufficient to judge if the trial was ethically justified, either due to a comparator that was not supported by the presented evidence (six protocols), because they did not present a rationale for conducting the trial (two protocols), or for both reasons (three protocols). For eight (12%) of the protocols, our search identified trials that could have been relevant to cite as justification. Conclusions While most protocols seem to adequately consider existing evidence, a substantial minority of trials might lack a sufficient evidence base. Very few trials seemed to have been based on a literature search which makes it impossible to know whether all relevant previous trials had been considered. Rules for ethical approval should include requirements for systematic literature searches to ensure that research participants are not exposed to sub-optimal treatments or unnecessary harms as well as to reduce research waste.

Drop-out rates in placebo-controlled trials of antidepressant drugs: A systematic review and meta-analysis based on clinical study reports.

Abstract: Objective To study the drop-out rates in trials of selective serotonin and serotonin-norepinephrine reuptake inhibitors (SSRIs and SNRIs). Methods This study is a systematic review and meta-analysis of trials. The main outcome measure: Overall drop-out rate. Secondary outcomes were drop-outs due to adverse events and lack of effect. We obtained clinical study reports (CSRs) of five antidepressant drugs from the European Medicines Agency and the UK's Medicines and Healthcare products Regulatory Agency. The eligibility criteria for selecting studies: double-blind randomised, placebo-controlled trials for any indication. Data extraction and analysis The primary outcome was extracted by two researchers independently and meta-analysed using the Mantel-Haenszel method (fixed effect model). The secondary outcomes were extracted by one researcher and checked by another. Sensitivity analyses were performed using Peto's odds ratio and beta binomial methods, due to presence of null events, and by excluding unreliable trials. Results We included 71 CSRs (67,319 pages) with information on 73 trials (11,057 patients on SSRI or SNRI drugs, and 7,369 on placebo). There were minor discrepancies within the CSRs when a modified intention to treat principle was used and patients lost to follow up early in the trial were not accounted for. Significantly more patients dropped out on active drug than on placebo, risk ratio 1.08 (95% CI 1.03 to 1.13), with no difference between adults and children/ adolescents, RR = 1.08 (1.03 to 1.13) and 1.07 (0.95 to 1.21), respectively. When three trials with a prior single-blind phase on active drug were removed, the difference was a risk ratio of 1.12 (1.07 to 1.18), whereas the result was the same after removal of three trials with fraudulent data or other issues with data validity, risk ratio 1.08 (1.03 to 1.13). There were more drop-outs due to adverse events on active drug than on placebo, risk ratio 2.63 (2.33 to 2.96). There were fewer drop-outs due to lack of effect, risk ratio 0.47 (0.43 to 0.53). However, this result is biased; when more people drop out due to adverse effects, fewer can drop out because of lack of effect. Conclusions By using CSRs, we were able to demonstrate for the first time that more patients dropped out on active drug than on placebo. As it can be argued that the drop-out rate reflects the patients' overall assessment of the balance between benefits and harms, our review adds to the growing concern that SSRIs and SNRIs might not have the desired effect. Our review also highlights the importance of using CSRs for undertaking reviews of drugs.

Long-term harms from previous use of selective serotonin reuptake inhibitors: A systematic review.

Abstract: Background Millions of people are treated with antidepressants like selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). This clinical practice is based on short-term trials that have exaggerated the benefits and underestimated the harms. We also know too little about long-term harms. Aim To assess harms of SSRIs and SNRIs that persist after end of drug intake. Methods Systematic review of placebo-controlled randomised trials of any length in patients with a psychiatric diagnosis and a follow-up of at least six months. Our primary outcomes were mortality, functional outcomes, quality of life and core psychiatric events. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials and checked the references for eligible articles. One researcher extracted data and another checked the data extraction. Results Our searches returned 9,153 unique records. We included 22 papers for 12 trials on SSRIs. Median intervention and follow-up periods were 15 and 52 weeks, respectively. Median number of randomised participants was 51; only two trials had a drop-out rate below 20%.Outcome reporting was less thorough during follow-up than for the intervention period and only two trials maintained the blind during follow-up. All authors concluded that the drugs were not beneficial in the long term.All trials reported harms outcomes selectively or did not report any. Only two trials reported on any of our primary outcomes (school attendance and number of heavy drinking days). Conclusion The randomised trials currently available cannot be used to investigate persistent harms of antidepressants.

Increased incidence of cervical cancer in Sweden: an unlikely link with human papillomavirus (HPV) vaccination

Abstract: In 2017, the Centre for Cervical Cancer Prevention in Sweden (NKCx) reported an increase in the Swedish cervical cancer incidence from 9.7/100 000 in 2006–2009 to 11.5/100 000 in 2014–2015 with a p value of 0.03 (see the Swedish report’s Table 9 on PDF page 49 of 87).1 In April 2018, the Indian Journal of Medical Ethics (IJME) published a comment entitled 'Increased incidence of cervical cancer in Sweden: possible link with HPV vaccination'. In May 2018, the comment was retracted, because its author had used a pseudonym, which violated IJME’s policy.2 Sweden’s human papillomavirus (HPV) vaccination programme was introduced in 2010, and the IJME comment author hypothesised that the increase in cervical cancer was possibly linked with HPV vaccination. Here, we argue why this is unlikely. In 2010, Sweden initiated its HPV vaccination programme for girls aged 12 to 15 years. The Swedish report included data up until the end of 2015 for women aged 20 years and older.1 Thus, very few of those who were included in the HPV vaccination programme were included in the Swedish report. In 2010, Sweden also conducted a catch-up vaccination programme for girls aged 15 to 18 years, who were 20 to 23 years old in 2015 and therefore included in the Swedish report.1 However, nearly half (41%) of this catch-up cohort was not HPV vaccinated, and …

Institute for Scientific Freedom.

Abstract: Scientific freedom and freedom of speech are constantly under attack because of financial, political, religious and other interests These essential values in democracies get eroded if we do not support them, fight against injustice and provide effective protection for whistle-blowers Fraud is another threat to the progress of science It is so common that a recent survey of 522 consulting US biostatisticians showed that 24% of them had experienced requests to remove or alter data to better support the research hypothesis1 If research results are unwelcome, they are often published with considerable delay, if at all, and often only after the researchers have modified their results or conclusions according to the wishes or demands of those who hold the power2 Self-censorship is also common Researchers may fear losing funding if they are honest, and powerful interests may influence what researchers choose to focus on and stay away from I have often heard advice from colleagues like, ‘Don’t step into this minefield’ or ‘It is shark-infested water’ It is far easier to get funding for mainstream projects with rather predictable results than running the risk of rocking the boat with …

What is the moral collapse in the Cochrane Collaboration about

Abstract: On September 13, 2018, one of the founders of the Cochrane Collaboration was expelled from the organisation, by a narrow vote of 6 to 5. Many see this as a moral collapse in what was once a magnificent grassroots organisation, guided by ethical principles and helping people make better decisions about healthcare interventions. I am that excommunicated person. I review here the essential issues leading to my expulsion, which occurred primarily because, in my capacity as a board member, I had challenged the CEO's virtually total control over the board, his mismanagement of Cochrane, and the direction in which he was taking the organisation. My criticism of psychiatric drugs and the highly prestigious Cochrane review of HPV vaccines also played a role. Freedom of Information requests revealed that the CEO went well beyond his brief to demand my removal from the Nordic Cochrane Centre, resulting in my sacking. Cochrane has become too close to industry and has introduced scientific censorship, which is detrimental for a scientific organisation. The board has announced a "zero tolerance" policy for repeated, serious bad behaviour. It would be beneficial if its CEO and board members applied this principle to themselves. I also discuss a recent paper by Trisha Greenhalgh et al that purported to have analysed the current Cochrane crisis in a disinterested fashion, which it did not. Instead of discussing the undeniable facts and the horrific abuses of power, TG consistently used positive terms about Cochrane and negative ones about me and my supporters.