Angell on Big Pharma

Some more truth about the pharmaceutical companies

Do pharmaceutical companies corrupt academic research and the clinical trial process ? You bet.

Dr Marcia Angell of Harvard Medical School and the author of The Truth About the Drug Companies talks with EconTalk host Russ Roberts about the impact of pharmaceutical companies on academic research, clinical trials and the political process. Angell argues that the large pharmaceutical companies produce little or no innovation and use their political power to exploit consumers and taxpayers. Reference.

Medical research publications : how to modify (abstracts) perception of negative (or non-significant) results into positive ones

Evaluation of Spin in the Abstracts of Emergency Medicine Randomized Controlled Trials

Spin is common (>40%) in emergency medicine randomized controlled trials…

May 2019 Study objective

We aim to investigate spin in emergency medicine abstracts, using a sample of randomized controlled trials from high-impact-factor journals with statistically nonsignificant primary endpoints.

Methods

This study investigated spin in abstracts of emergency medicine randomized controlled trials from emergency medicine literature, with studies from 2013 to 2017 from the top 5 emergency medicine journals and general medical journals. Investigators screened records for inclusion and extracted data for spin. We considered evidence of spin if trial authors focused on statistically significant results, interpreted statistically nonsignificant results as equivalent or noninferior, used favorable rhetoric in the interpretation of nonsignificant results, or claimed benefit of an intervention despite statistically nonsignificant results.

Results

Of 772 abstracts screened, 114 randomized controlled trials reported statistically nonsignificant primary endpoints. Spin was found in 50 of 114 abstracts (44.3%). Industry-funded trials were more likely to have evidence of spin in the abstract (unadjusted odds ratio 3.4; 95% confidence interval 1.1 to 11.9). In the abstracts’ results, evidence of spin was most often due to authors’ emphasizing a statistically significant subgroup analysis (n=9). In the abstracts’ conclusions, spin was most often due to authors’ claiming they accomplished an objective that was not a prespecified endpoint (n=14).

Conclusion

Spin was prevalent in the selected randomized controlled trial, emergency medicine abstracts. Authors most commonly incorporated spin into their reports by focusing on statistically significant results for secondary outcomes or subgroup analyses when the primary outcome was statistically nonsignificant. Spin was more common in studies that had some component of industry funding.

EU requirements to provide results for authorised clinical trials – EC, EMA, MHA

Call for all sponsors to publish clinical trial results in EU database (joint letter by the European Commission, EMA and HMA)

 

The European Commission (EC), the European Medicines Agency (EMA) and the Heads of Medicines Agencies (HMA) have co-signed a letter reminding all sponsors of clinical trials conducted in the European Union of their obligation to make summaries of results of concluded trials publicly available in the EU Clinical Trials Database (EudraCT).

Transparency and public access to clinical trial results, whether positive or negative, are fundamental for the protection and promotion of public health. It assures trial subjects that their voluntary participation in clinical trials is useful and that the results have been collated and reported for the benefit of all. In addition, for those medicines which are placed on the market or used in further clinical trials, it allows patients and healthcare professionals, or any other citizen, to find out more information about medicines they might be taking or prescribing. Transparency also enhances scientific knowledge and helps to advance clinical research and support more efficient medicine development programmes.

It is the responsibility of sponsors to ensure that the protocol information and results of all clinical trials is submitted in EudraCT; this information is publicly available through the EU Clinical Trials Register (EU CTR). Since July 2014, sponsors are required to post results within one year after the end of a clinical trial (or six months for a paediatric trial). This information is also shared with the World Health Organization’s (WHO) International Clinical Trials Registry Platform (ICTRP) of which EU CTR is a primary registry.

As of April 2019, the EudraCT database included 57,687 clinical trials in total, out of which 27,093 were completed. Out of these completed trials, 18,432 should have had results posted; sponsors were in compliance with the publication requirements for 68.2% (12,577) of the trials, however results were still lacking for 31.8% of them (5,855).

The reporting compliance of non-commercial sponsors (e.g. academia) was much lower than for commercial sponsors (i.e. companies), with 23.6% of results posted for non-commercial sponsors vs 77.2% for commercial sponsors. Academic sponsors or smaller companies often lack awareness or incentives to post clinical results, therefore EU authorities are taking various steps to ensure sponsors are aware of their obligations and can act on them.

One of these initiatives is the “letter to stakeholders regarding the requirements to provide results for authorised clinical trials in EudraCT”, co-signed by Anne Bucher, Director General of the EC’s DG Health and Food Safety, Guido Rasi, Executive Director of EMA, and Thomas Senderovitz, Chair of the HMA Management Group. It will be disseminated to various stakeholder groups, with a goal in particular to reach academic sponsors. This should help to spread the word about the importance of making clinical trial results publicly available.

Amongst other initiatives conducted at EU level, EMA has since September 2018 been identifying trials with missing results on a monthly basis and sending reminders to the sponsors of those trials to ensure compliance with the transparency rules and their follow up on their results reporting obligations.

Reference.

Clinical Trials on Vaccines : the Revelations of a Doctor

Meehan MD on the poor science of the recent Danish MMR Autism Study

Published on 6 March 2019, by Jim Meehan, MD

 

The James Lind Library’s Introduction to Fair Tests of Treatments

JLL Book of Essays, About Fair Tests, May 2019

Introduction

At various times in our lives and to varying levels of intensity, we all use, provide or pay for health and social care. As we decide what to do, take, offer or buy, we need evidence that is reliable, robust and trustworthy about different options. Even before James Lind’s experiment comparing possible treatments for scurvy on HMS Salisbury people had recognised that getting this evidence requires strenuous efforts to reduce bias –but that achieving this is often not straightforward. This book of essays from the James Lind Library is our attempt to illustrate some of the challenges encountered and how to overcome them.

We will take you on a journey through the sometimes stormy waters of why treatments need to be tested, rather than being based on assumptions that “it must work” before the treatment has even been tried, or based on impressions after it has been used a few times, through to the need for fair tests comparing alternative treatment options. We will show why genuine uncertainties must be identified and addressed, and how research to find the most effective and appropriate treatments need to build on research to identify the most effective and appropriate methods for doing that research. We will navigate through the reasons why comparisons need to be fair at the outset, and then kept fair as the treatments being tested are given;outcomes are measured;and results are analysed, reported, and combined in systematic reviews of all the relevant, trustworthy evidence.

We have not cluttered the chapters with references to all the source material on which we have drawn. For that level of detail, please follow the links to the fuller essays on the James Lind Library website. Instead, where we know of reviews of methodology research which are relevant to a topic, we have listed these at the end of each chapter.

By the end of the book, we hope that you will recognise how, to bring benefits of research to patients and the public, systematic reviews of fair tests are needed to provide key elements of the knowledge needed to inform decisions about health and social care, while taking into account other important factors, such as values, preferences, needs, resources and priorities. We also hope that, as you finish the book, you will share the sense of enlightenment, education and enjoyment that we have gained from preparing it.

Finally, we dedicate this book to England’s National Institute for Health Research. Without the Institute’s 16-year-long support for the James Lind Initiative, the home of the James Lind Library during that time, neither the Library nor these essays would have been possible. And we also wish to acknowledge the role the Institute plays in recognising the vital contribution of research to the delivery of health and social care that is effective and efficient, and the Institute’s leadership in ensuring that the research itself is effective, efficient and reliable, with minimal waste.

Abstract

1.3 Why treatment comparisons must be fair

Untrustworthy treatment comparisons are those in which biases, or the play of chance, or both result in misleading estimates of the effects of treatments. Fair treatment comparisons avoid biases and reduce the effects of the play of chance.

It is not only failure to test theories about treatments in practice that has caused preventable tragedies. They have also occurred because the tests used to assess the effects of treatments have been unreliable and misleading. In the 1950s, theory and poorly controlled tests yielded unreliable evidence suggesting that diethylstilboestrol (DES) helped pregnant women who had previously had miscarriages and stillbirths. Although fair tests suggested that DES was useless, theory and unreliable evidence, together with aggressive marketing, led to DES being prescribed to millions of pregnant women over the next few decades. The consequences were disastrous for the women and their children, who experienced infertility and cancers as a result. The lesson is that a treatment that has not been reliably shown to be useful should not be promoted.

Problems resulting from inadequate tests of treatments continue to occur. Again, because of unreliable evidence and aggressive marketing, millions of women were persuaded to use hormone replacement therapy (HRT). It was claimed that, not only could it reduce unpleasant menopausal symptoms, but also the chances of having heart attacks and strokes. When these claims were assessed in fair tests, the results showed that in women over 60, far from reducing the risks of heart attacks and strokes, HRT increases the risks of these life-threatening conditions, as well as having other undesirable effects.These examples of the need for fair tests of treatments are a few of many that illustrate how treatments can do more harm than good. Improved general knowledge about fair tests of treatments is needed so that –laced with a healthy dose of scepticism –we can all assess claims about the effects of treatments more critically. That way, we will all become more able to judge which treatments are likely to do more good than harm.

DES DiEthylStilbestrol Resources

Meet the people who lived with defective devices

Implant Files, video published by ICIJ, 25 November 2018

ICIJ listened to hundreds of stories from patients with poorly-functioning medical devices. Here are just five of their testimonies.

Read more about ICIJ implant files investigation.

ICIJfights corruption with the world’s best cross-border watchdog journalism by over 160 investigative reporters in 60+ countries. The home of Offshore Leaks.”

Why join the Implant Files investigation ?

Implant Files, video published by ICIJ, 25 November 2018

Journalists explain why they decided to investigate medical device harm with ICIJ reporters.

Read more about ICIJ implant files investigation.

ICIJfights corruption with the world’s best cross-border watchdog journalism by over 160 investigative reporters in 60+ countries. The home of Offshore Leaks.”

A global investigation into medical device harm

Implant Files, video published by ICIJ, 24 November 2018

Patients around the world have become unwitting test subjects for new medical technology. Often following the trusted advice of their doctors, they have been injured, maimed and killed by poorly-tested implants.

Read more about the their implant files investigation.

ICIJfights corruption with the world’s best cross-border watchdog journalism by over 160 investigative reporters in 60+ countries. The home of Offshore Leaks”.

Major US funders ($$ billions) are pushing for greater clinical trials transparency

Noncommercial US Funders’ Policies on Trial Registration, Access to Summary Results, and Individual Patient Data Availability

2019 Study Key Points

  • Question
    What are the current policies for clinical trial registration, summary results sharing, and individual patient data sharing among the top 10 noncommercial US health research funders?
  • Findings
    In this review study, 6 of 9 (67%) of the top US funders have a publicly available written policy addressing all 3 major trial transparency domains. However, fewer US funders require specific transparency actions in these domains (11%-56%) or monitor compliance with their policies (56%-67%).
  • Meaning
    More work remains to be done to ensure timely implementation and enforcement of clinical trial transparency initiatives to reduce waste and realize public value from clinical research investments.

Abstract

Importance
Incomplete information about existing research is an underlying cause of research waste. National and international initiatives and requirements have been launched to address this issue.

Objectives
To characterize current clinical trial transparency policies among the largest noncommercial US funders and examine whether the policies are concordant with international funders.

Design, Setting, and Participants
This retrospective review of public information used methods developed for documenting funder policies internationally; 2 researchers searched each funder’s website and Google between May and November 2018 to locate trial transparency policies for 10 top US funders. Key informants at each funding organization were contacted by email and given 3 or more weeks to review and confirm or correct the findings. Nonresponders were contacted 2 or more additional times. Descriptive statistics were calculated to summarize the findings. The study was conducted using publicly available policy information with findings confirmed by funder representatives where possible. Participants included top 10 noncommercial US health research funders with the highest reported investment in health research (2013 dollars) who fund clinical trials. Data analysis was conducted from November 6, 2018, to November 23, 2018.

Exposures
Availability of policies addressing each of the 3 key trial transparency domains as specified by the World Health Organization in 2017.

Main Outcomes and Measures
Independent assessment by 2 investigators of availability (yes or no) of a policy addressing registration for trials, sharing of summary results, and individual participant data sharing activities; requirements (yes, no, or supportive statement) of these policies in terms of completeness, timeliness, public access, and provision of additional technical or financial support to meet data sharing requirements; description (yes or no) of internal monitoring for policy adherence.

Results
All 10 funders acknowledged the outreach. One funder who indicated that less than 1% of their research funding goes to clinical trials was removed. Six (67%) of the remaining 9 top US funders have a publicly available written policy for all 3 major trial transparency domains. The most comprehensive trial transparency practice among US funders addresses summary results sharing as follows: 8 of 9 US funders (89%) have a policy, 5 of 9 US funders (56%) require reporting of summary results within 1 year, and 6 of 9 US funders (67%) monitor compliance with their summary results sharing policy. For clinical trial registration, 7 of 9 US funders (78%) have a policy and 5 of 9 US funders (56%) require registration and monitor trial registration to measure adherence to the policy.

Conclusions and Relevance
In this study, overall the proportion of US funders with policies and practices to support trial transparency in this sample was similar or compared favorably with the larger international sample of noncommercial funders recently reported.

 

Unbiased information on medicines : Why is it needed?

Pharmaceutical promotion practices HAI webinar, Oct 2018

Dr Barbara Mintzes (University of Sydney) joins Health Action International for an expert webinar on pharmaceutical promotion practices.