Cochrane HPV vaccine review not found to be ‘Trusted Evidence’

The Cochrane HPV vaccine review was incomplete and ignored important evidence of bias

In May 2018, the Cochrane Collaboration published its review of the human papillomavirus (HPV) vaccines. The review primarily assessed the vaccines’ effect on precursors to cervical cancer. Cochrane has high standards for its reviews; however, there were important limitations in its HPV vaccine review, which we address in this paper.

Key findings

  • The Cochrane human papillomavirus (HPV) vaccine review missed nearly half of the eligible trials
  • No included trial in the Cochrane review used a placebo comparator
  • The included HPV vaccine trials used composite surrogate outcomes for cervical cancer
  • The Cochrane review incompletely assessed serious and systemic adverse events
  • The Cochrane review did not assess HPV vaccine-related safety signals
  • Industry trial funding and other conflicts of interest
  • Cochrane’s public relations of the review were uncritical

Conclusion

Part of the Cochrane Collaboration’s motto is ‘Trusted evidence’. We do not find the Cochrane HPV vaccine review to be ‘Trusted evidence’, as it was influenced by reporting bias and biased trial designs. We believe that the Cochrane review does not meet the standards for Cochrane reviews or the needs of the citizens or healthcare providers that consult Cochrane reviews to make ‘Informed decisions’, which also is part of Cochrane’s motto. We recommend that authors of Cochrane reviews make every effort to identify all trials and their limitations and conduct reviews accordingly.

Read the author’s full paper on The BMJ.

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Deadly Psychiatry and Organised Denial

Why the way we currently use psychiatric drugs does far more harm than good

Unfortunately, psychiatry has, to a considerable extent, abandoned the biopsychosocial disease model and now uses almost exclusively a biomodel, which means using drugs as the “solution” for all problems. This approach to psychiatry has failed to deliver what the patients want, and it has had serious consequences. Most patients don’t respond to the drugs they receive and unfortunately, the psychiatrists’ frustrations over the lack of progress often lead to institution of more drugs and higher doses, harming the patients further. There is no doubt that the way we currently use psychiatric drugs does far more harm than good. Psychiatric drugs are so harmful that they kill more than half a million people every year among those aged 65 and above in the United States and Europe. This makes psychiatric drugs the third leading cause of death, after heart disease and cancer. We could reduce our current usage of psychotropic drugs by 98% and at the same time improve people’s mental health and survival. There is nothing psychiatric patients fear more than forced treatment, and this is an important reason why having close contact with the psychiatric treatment system markedly increases suicides. According to a United Nations convention, forced treatment is a violation of human rights and must be banned, and empirical data have shown that a psychiatry without forced treatment is possible. Peter C. Gøtzsche, a professor in clinical research design and analysis, specialist in internal medicine, and founder of the Nordic Cochrane Centre, is a world leader in his field. His research and professional integrity enjoys great international respect, and this book will be published simultaneously with the Danish version. This is one of the most scientifically and academically substantiated indictments ever directed against one of the world’s largest and most powerful industries.

Why prescription drugs are now the third leading cause of death and the pharmaceutical manufacturers dominance of mental healthcare

James Moore interviews Professor Peter Gøtzsche, Nordic Cochrane Centre Director, 2017

James Moore was keen to talk to Prof. Peter Gøtzsche about his background in research, his views on antidepressant prescribing and how pharmaceutical manufacturers have influenced mental healthcare.

Overview

  • Professor Gøtzsche’s background in clinical trials within the Pharmaceutical industry.
  • How the pharmaceutical manufacturers were manipulating clinical trial data for their own gain.
  • How drug manufacturers have denied for more than 20 years that benzodiazepines and antidepressant drugs cause dependance.
  • How the UK drug regulator (MHRA) also denied this in 2003 at the same time that the World Heath Organisation reported that 3 antidepressants were in the top 30 list of drugs that create dependance.
  • That surveys of patients show that between 50% and 66% of those taking antidepressants experience dependance.
  • The similarities between the pharmaceutical industry and the tobacco industry.
  • That stopping an antidepressant suddenly can be very dangerous.
  • How prescription drugs have become the third leading cause of death behind heart disease and cancer.
  • How pharmaceutical manufacturers have used their power and influence to the detriment of patient safety.
  • That the best science shows that there is no doubt that psychiatric drugs have killed millions of people over the years.
  • How psychotherapy is shown to reduce the risk of suicide but instead we prescribe pills that increase the suicide risk for all ages of patients.
  • That the chemical imbalance lie is still being propagated amongst psychiatrists even thought here is no scientific evidence whatsoever so support it.
  • How psychiatric drugs should be used for acute/emergency situations only.
  • That the medication centred approach of psychiatry does more harm than good.
  • How patients should avoid psychiatric drugs unless they are used for a very short time or that the patient really feels that they need them.
  • That when you look at the randomised controlled trials, there is a large risk of bias in these trials and that antidepressant efficacy has been overstated.
  • That the Cochrane Collaboration undertook the most rigorous meta analysis ever undertaken of 131 trials involving 27,422 patients taking SSRI’s, this analysis showed that antidepressants do not have any meaningful effects and their harms outweigh any benefits there might be.

Sources

How to eliminate the risk of the third leading cause of death

Dr Peter Gøtzsche’s views on prescription drugs

Video published on 1 April 2015 by John McDougall.

Peter C. Gøtzsche, MD is a Danish medical researcher, and leader of the Nordic Cochrane Center at Rigshospitalet in Copenhagen, Denmark. He has written numerous reviews within the Cochrane collaboration.

Dr.Gøtzsche has been critical of screening for breast cancer using mammography, arguing that it cannot be justified; His critique stems from a meta-analysis he did on mammography screening studies and published as Is screening for breast cancer with mammography justifiable? in The Lancet in 2000. In it he discarded 6 out of 8 studies arguing their randomization was inadequate.

In 2006 a paper by Gøtzsche on mammography screening was electronically published in the European Journal of Cancer ahead of print. The journal later removed the paper completely from the journal website without any formal retraction. The paper was later published in Danish Medical Bulletin with a short note from the editor, and Gøtzsche and his coauthors commented on the unilateral retraction that the authors were not involved in.

In 2012 his book Mammography Screening: Truth, Lies and Controversy was published. In 2013 his book Deadly Medicines and Organized Crime: How Big Pharma has Corrupted Healthcare was published.

How to reduce your risk of becoming a breast cancer patient by one third

Dr Peter Gøtzsche’s views on breast cancer screening

Video published on 1 April 2015 by John McDougall.

Peter C. Gøtzsche, MD is a Danish medical researcher, and leader of the Nordic Cochrane Center at Rigshospitalet in Copenhagen, Denmark. He has written numerous reviews within the Cochrane collaboration.

Dr.Gøtzsche has been critical of screening for breast cancer using mammography, arguing that it cannot be justified; His critique stems from a meta-analysis he did on mammography screening studies and published as Is screening for breast cancer with mammography justifiable? in The Lancet in 2000. In it he discarded 6 out of 8 studies arguing their randomization was inadequate.

In 2006 a paper by Gøtzsche on mammography screening was electronically published in the European Journal of Cancer ahead of print. The journal later removed the paper completely from the journal website without any formal retraction. The paper was later published in Danish Medical Bulletin with a short note from the editor, and Gøtzsche and his coauthors commented on the unilateral retraction that the authors were not involved in.

In 2012 his book Mammography Screening: Truth, Lies and Controversy was published. In 2013 his book Deadly Medicines and Organized Crime: How Big Pharma has Corrupted Healthcare was published.

Breast cancer screening not associated with a reduction in the incidence of advanced cancer

Mammograms tied to overdiagnosis of breast cancer

The current study offers fresh evidence linking routine screening to over-diagnosis of non-aggressive tumors because it compares outcomes over a single time period in two regions of Denmark – one that offered biennial mammography for women aged 50 to 69 and one that didn’t.

January 2017 Study Abstract

Background
Effective breast cancer screening should detect early-stage cancer and prevent advanced disease.

Objective
To assess the association between screening and the size of detected tumors and to estimate overdiagnosis (detection of tumors that would not become clinically relevant).

Design
Cohort study.

Breast Cancer Screening in Denmark: A Cohort Study of Tumor Size and Overdiagnosis, Annals of Internal Medicine, DOI: 10.7326/M16-0270, 10 JANUARY 2017.

Philips Mammography Truck, Brazil via philips_newscenter.

Setting
Denmark from 1980 to 2010.

Participants
Women aged 35 to 84 years.

Intervention
Screening programs offering biennial mammography for women aged 50 to 69 years beginning in different regions at different times.

Measurements
Trends in the incidence of advanced (>20 mm) and nonadvanced (≤20 mm) breast cancer tumors in screened and nonscreened women were measured. Two approaches were used to estimate the amount of overdiagnosis: comparing the incidence of advance and nonadvanced tumors among women aged 50 to 84 years in screening and nonscreening areas; and comparing the incidence for nonadvanced tumors among women aged 35 to 49, 50 to 69, and 70 to 84 years in screening and nonscreening areas.

Results
Screening was not associated with lower incidence of advanced tumors. The incidence of nonadvanced tumors increased in the screening versus prescreening periods (incidence rate ratio, 1.49 [95% CI, 1.43 to 1.54]). The first estimation approach found that 271 invasive breast cancer tumors and 179 ductal carcinoma in situ (DCIS) lesions were overdiagnosed in 2010 (overdiagnosis rate of 24.4% [including DCIS] and 14.7% [excluding DCIS]). The second approach, which accounted for regional differences in women younger than the screening age, found that 711 invasive tumors and 180 cases of DCIS were overdiagnosed in 2010 (overdiagnosis rate of 48.3% [including DCIS] and 38.6% [excluding DCIS]).

Limitation
Regional differences complicate interpretation.

Conclusion
Breast cancer screening was not associated with a reduction in the incidence of advanced cancer. It is likely that 1 in every 3 invasive tumors and cases of DCIS diagnosed in women offered screening represent overdiagnosis (incidence increase of 48.3%).

If screening had been a drug, it would have been withdrawn from the market

Which country will be first to stop mammography screening?

Key points

  • Screening with mammography does not reduce the occurrence of advanced cancers.
  • Rigorous observational studies in Europe have failed to find an effect of mammography screening.
  • Mammography screening produces patients with breast cancer from among healthy women and increases the number of mastectomies performed.
  • The most effective method we have to reduce the occurrence of breast cancer is to stop screening.

Time to stop mammography screening?

The Canadian Task Force on Preventive Health Care should be congratulated for its new recommendations on screening for breast cancer in women at average risk aged 40–74 years. These guidelines are more balanced and more in accordance with the evidence than any previous recommendations.

The recommendations against routine clinical breast examinations, breast self-examinations and magnetic resonance imaging to screen for breast cancer in this age and risk group are all straightforward.

The recommendations on mammography screening are even more conservative than the change in policy suggested by the US Preventive Services Task Force in 2009, which created an uproar in the United States from people interested in maintaining the status quo. The new Canadian guidelines are appropriately cautious, advising against routinely screening women aged 40–49 years. The task force recommends screening women aged 50–69 years every two to three years, although it admits that this is a weak recommendation based on moderate-quality evidence, and screening women aged 70–74 years on the same schedule based on low-quality evidence. The task force also suggests that women who do not place a high value on a small reduction in breast cancer mortality, and who are concerned with false-positive results on mammography and overdiagnosis, may decline screening.

These guidelines are an important step in the right direction, away from the prevailing attitude that a woman who does not undergo screening is irresponsible. Recent research even suggests that it may be most wise to avoid screening altogether, at any age, as outlined below.

The Canadian Task Force on Preventive Health Care decided not to include observational studies in its systematic review unless they were needed to elucidate the harms of screening or the values and preferences of patients. However, important observational studies have been published in recent years, without which a systematic review would be incomplete. These observational studies have been discussed elsewhere and have also been included in an update (currently submitted for publication) of our 2009 Cochrane review of mammography screening.

Doubtful effect of screening

Time to stop mammography screening?; National Institutes of Health PMC3225414 183(17): 1957–1958, Nov 22 2011.

Programming a latest-gen mammography station, nicoyogui.

If screening does not reduce the occurrence of advanced cancers, it does not work. A systematic review of studies from seven countries showed that, on average, the rate of malignant tumours larger than 20 millimetres was not affected by screening. Because the size of a tumour is linearly correlated to the risk of metastasis, this result is evidence against an effect of screening.

Denmark has a unique control group within its population — only 20% of its population was screened during a 17-year period. The annual decrease in breast cancer mortality in the relevant age group (55–74 years) and period was 1% in the areas with screening and 2% in the non-screened areas.Among women who were too young to benefit from screening, the decreases were larger (5% for screened areas, 6% for unscreened areas). Similar results have been reported from the United Kingdom, Sweden and Norway.

A study involving women from 30 European countries showed that the mean decrease in breast cancer mortality between 1989 and 2005 among women less than 50 years of age was 37%; the corresponding decrease was 21% among women aged 50–69 years. The declines began before the start of organized screening programs in many countries and are more likely explained by the introduction of tamoxifen. The introduction of tamoxifen could explain the larger decline seen among young women who often have estrogen-sensitive tumours.

Another study compared three pairs of similar neighbouring countries that had introduced screening 10–15 years apart. The pairs were Northern Ireland and the Republic of Ireland, the Netherlands and Belgium, and Sweden and Norway. There was no relation between start of screening and the reduction in breast cancer mortality.The fall in breast cancer mortality was about the same in all countries. Furthermore, the decline was also about the same as that seen in the United States, where screening started as early as in Sweden.

Screening seems to be ineffective in today’s world for two reasons. First, adjuvant therapy, such as tamoxifen and chemotherapy, is highly effective (even when the cancer has metastasized) but was not often used at the time of the old trials. Second, public awareness of breast cancer has increased, and women tend to see a doctor much earlier today when they have noticed something unusual in their breast. In Denmark, the average size of a tumour decreased by nine millimetres from 1979 to 1989, a reduction that occurred before screening started. In addition, this decrease was larger than the average difference in tumour size seen between screened and control groups in trials (5 mm), despite the tendency for small, overdiagnosed tumours to spuriously exaggerate the difference.

It has often been claimed that mammography screening reduces breast cancer mortality by 30%. However, thorough systematic reviews have estimated only a 15% reduction, and data on tumour size from the trials are compatible with only a 12% effect.This effect is similar to the results seen in the most reliable studies, which showed a 10% effect after 13 years.

Overdiagnosis

Any possible effect of screening on breast cancer mortality must be marginal and could be counteracted by the life-shortening effect that radio-therapy and chemotherapy have when used in healthy women in whom breast cancer has been overdiagnosed (i.e., a diagnosis of breast cancer that would not have been made in the woman’s remaining life had she not undergone screening). The main effect of screening is to produce patients with breast cancer from among healthy women who would have remained free of breast disease for the rest of their lives had they not undergone screening. Compelling data from the US, Norway and Sweden show that most overdiagnosed tumours would have regressed spontaneously without treatment.  In addition, screening substantially increases the number of mastectomies performed, despite routine claims to the contrary by advocates of screening.

The best method we have to reduce the risk of breast cancer is to stop the screening program. This could reduce the risk by one-third in the screened age group, as the level of overdiagnosis in countries with organized screening programs is about 50%.

If screening had been a drug, it would have been withdrawn from the market. Thus, which country will be first to stop mammography screening?

Peter Gøtzsche, MD, 2011.

Pharma Industry fear a Boycott more than anything else

” I don’t think industry are concerned about patient confidentiality except in so far as they are concerned to avoid being sued for injuries in clinical trials. ”

There is a very informative and fascinating debate going on between Dr David Healy and Ben Goldacre regarding options, thoughts, strategies for better clinical trials access and transparency.
Dr. David Healy posted “fuckedhere and I posted a summary here.
Dr Ben Goldacre responded here and here. I republished his reply here.
Dr. David Healy then clarified here – see below – I only added few related links (in the original text response) with the purpose to bring more clarity and/or references to the readers.

Again let me invite you to read “fucked” post 22 comments – about clinical trial data access and pharmaceutical industry transparency.

image of David Healy
David Healy is professor of psychiatry and co-founder of data based medicine, operating through RxISK.org , working towards making medicines safer.

The first point to make is this post isn’t about AllTrials.
AllTrials is a footnote.

It’s about the dismay that many felt at EMA backsliding. It’s about how it was obvious that something like this was on the cards. Against this background uncritical endorsement of industry looked like a bad idea. There was a desperate need to stay awake. It looks like too many of us have been asleep.
Ben offers an outline of the AllTrials strategy here. It’s helpful to have this.
His accusation that these posts misrepresent campaigns, smear people, shout abuse, and hector from the sidelines looks like a description of posts by others elsewhere. With very few exceptions any comments to the various posts on this blog that in any way fail to support Ben or AllTrials have been deleted.
The post repeated an alternate analysis – that the main thing industry wants to hide are adverse event data.
In a post 18 months ago I outlined how to achieve this industry would in public deploy the issue of patient confidentiality as a main justification for hiding data. In this it seems to me they have been assisted by Iain Chalmers editorial with Patrick Vaillance and now by Ben.
The historical evolution of the confidentiality issue is that the first informed consent forms said nothing about not showing your data to anyone else. Unnoticed industry have slipped in a “we will of course show your data to no-one clause”.
At the EMA conference on data access in November 2012, I made two points. The second was that industry would assert the notion of their privacy rights – which they have done. The other was that no one signs to have their data sequestered. Afterwards, Iain Chalmers congratulated me on the point – I thought we were on the same page.
Whether adverse event data is key or not, Peter Gotzsche through the European Ombudsman and Tom Jefferson and Peter Doshi through Tamiflu and RIAT seem to me to have done more in practical terms to move the issues forward than anyone else. It leaves me wondering why there is an endless call to celebrate Ben and not Peter or Tom.
Some of us have been working the GSK system and can see what the pitfalls are. Even if not redacted, this is a system that will make it close to impossible to analyse CSRs properly. But if it’s not proclaimed by AllTrials first it seems like such insights are unwelcome.
In several posts before the latest debacle I outlined how in my opinion there was a real chance that magnificent though he has been and clearly morally right, Peter Gotzsche’s efforts may do more harm than good. Even without taking GSK’s preposterous data access system into account, pushing for data adds to the undue premium being put on RCTs Twenty years ago the moral case for access was as strong and the risks consequent on failing were much less in that we were less hypnotized by RCTs than we are now.
Far from responding shrilly, Peter Gotzsche recognized the risk and we have been collaborating ever more closely since. The issues are so complex we might all be making mistakes – the only people unwilling to concede this seem to be AllTrials.
The push for data access remains morally compelling but there are other things that can be done that might be more effective.
As the BBC program a week ago on Thalidomide, and previous posts here, make clear, industry fear a boycott more than anything else. It is the only thing they have ever responded to.
At the moment the focus is on a bunch of bureaucrats in EMA, who aren’t there with a brief to protect us other than by regulating the wording of advertisements.
The focus should be on doctors who treat patients. We could refuse to use drugs where there is no access to the data. It shouldn’t even take courage to do this. In my opinion, this is the call that’s needed now rather than a call to support more of what AllTrials have been doing. But who will lead such a call?
Along with colleagues I put forward a softer version of a boycott – an AbbVie – which encouraged doctors and patients to use drugs but to report on the adverse events which would in fact make these chemicals better medicines. It would be difficult for government or anyone else to gainsay this win-win option in the way they might come out against the lose-lose of a boycott.
There is a conflict of interest here. RxISK.org has a stake in this idea. It was set up before AllTrials to move ideas like this forward. I suspect those of us working on RxISK in the evenings and at weekends have been putting far more hours into the effort than the AllTrials team have.
At the end of the day, I may well be wrong on this, but I personally think AllTrials have been naïve. I don’t think industry are concerned about patient confidentiality except in so far as they are concerned to avoid being sued for injuries in clinical trials.
Recent decades have seen industry put Litigation Support Defences in place. As outlined a decade ago in Let Them Eat Prozac, putting a premium on clinical trials has been a key element in their litigation support strategy. Seen from this vantage point AllTrials offers Pharma a lot – all without the effort of having to conspire or fund a conspiracy.
Playing straight into industry’s hands is a hazard for all of us. Good intentions aren’t enough to save us. I’d rest more comfortably if the key players in AllTrials had a track record in bringing adverse events to light or even a record of supporting those trying to do so – if they’d really antagonized industry good and proper. It’s not that partnership isn’t nice but perhaps after playing hard to get first. ”

Find all our posts about the AllTrials campaign, Clinical trials, Dr Ben GoldacreDr. David HealyGlaxoSmithKlinePeter Gøtzsche and Sir Iain Chalmers.

UK Medicines Regulator MHRA destroys Prozac Research and Clinical Trial Data after 15 Years on File

UK meds regulator destroys detailed information on the benefits and harms of drugs it has approved after it has held it for 15 years on file

image of the MHRA logo
The MHRA UK medicines regulator destroys detailed information on the benefits and harms of drugs it has approved after it has held it for 15 years on file.

BRITAIN’S medicines regulator has destroyed the original scientific data supporting the licensing of Prozac, the antidepressant drug that is provoking growing controversy over evidence that it is linked to suicide.

It means that scientists who have tried to re-examine the evidence justifying its release may now never be able to find out how good the science was. Patients making compensation claims will face the same problem.

The UK medicines regulator destroys detailed information on the benefits and harms of medicines it has approved after it has held it for 15 years. This means that for medicines which have been on the market for longer than 15 years, which is the majority of them, the Medicines and Healthcare Products Regulatory Agency (MHRA) no longer holds the data it based its licensing decision on.

This came to light after Professor Peter Gotzsche, co-founder of the Cochrane Collaboration, asked the European Medicines Agency for the data used to support the licensing of the antidepressant Prozac (fluoxetine). Gotzsche was referred to the MHRA as the UK is designated as the Reference Member State for Prozac meaning the MHRA is the nominated body within the EU that holds the information on the drug. Never the less, the MHRA had shredded clinical evidence about the benefits and harms of the product. It told Professor Gotzsche “Under MHRA record management policy, all application files and data for licences are held for 15 years. After this period, files are destroyed unless there is a legal, regulatory, or business need to keep them, or unless they are considered to be of lasting historic interest.”

The Sunday Times reported yesterday that “the MHRA said it had shredded the detailed information and held only some documents that summarised the findings. Eli Lilly, the manufacturer, retains the data and the MHRA said it can order it to be submitted.”

Professor Gotzsche wrote in a letter in the BMJ in June 2011 “As citizens in the EU, we should not accept this state of affairs. … The UK government should introduce legislation that will prevent the MHRA in future from destroying the evidence in its possession.”

Dr Ben Goldacre, co-founder of AllTrials said: “The MHRA needs to recognise that the world has changed, it is no longer acceptable for decisions about medicines to be based on secret meetings, about secret information that is then shredded. Doctors, researchers and patients need access to all the evidence, to make fully informed decisions about which treatment is best, and help spot problems with treatments as quickly as possible. Science progresses, and medicine improves, when we have many eyes on the data.”

Sources:
  • MHRA shreds clinical trial info after 15 years, AllTrials.net, News release, 24th March 2014
More information, letters, opinions and articles:
  • Drug regulator destroys Prozac research, TheSundayTimes, 23 March 2014
  • and take names… , 1boringoldman, 23 March 2014
  • MHRA destroys trial data after 15 years on file, PharmaTimes, 23 March 2014
  • Restoring invisible and abandoned trials: a call for people to publish the findings, BMJ 346:f2865, 13 June 2013
  • UK drug regulator destroys all evidence after 15 years, BMJ 343:d4203, 5 July 2011
  • Opening up data at the European Medicines Agency, BMJ rapid-response, 20 June 2011
  • Opening up data at the European Medicines Agency, BMJ 342:d2686, 10 May 2011
  • UK Drug Regulator Destroys All Trial Data After 15 Years, Medscape 746109, July 11, 2011

Deadly Medicines and Organized Crime: a Video Conference with Peter Gøtzsche

Prescription drugs are the third leading cause of death after heart disease and cancer

Tholduset, Helsingor, October 3, 2013

Conference with Peter Gøtzsche – Director of the Nordic Cochrane Center and Co-Founder of The Cochrane Collaboration – on the topic of his book Deadly Medicines and Organized Crime: How Big Pharma has Corrupted Healthcare.

More info and Videos
  • Video by Poet Dox, Published on 17 Oct 2013.
  • More videos via YouTube.