AllTrials

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AllTrials (sometimes called All Trials or AllTrials.net) is a project advocating that clinical research adopt the principles of open research. The project summarizes itself as "All trials registered, all results reported": that is, all clinical trials should be listed in a clinical trials registry, and their results should always be shared as open data.

Contents

At the center of the organisation is a petition signed by over 85,000 individuals and 599 organisations (as of August 2015):

Thousands of clinical trials have not reported their results; some have not even been registered.

Information on what was done and what was found in these trials could be lost forever to doctors and researchers, leading to bad treatment decisions, missed opportunities for good medicine, and trials being repeated.

All trials past and present should be registered, and the full methods and the results reported.

We call on governments, regulators and research bodies to implement measures to achieve this.

Ben Goldacre, author of Bad Science and Bad Pharma , is a founder of the campaign and its most public spokesperson. In 2016, he participated in the launch of the OpenTrials database. [1]

AllTrials is an international initiative of Bad Science, BMJ , Centre for Evidence-based Medicine, Cochrane Collaboration, James Lind Initiative, PLOS and Sense about Science and is being led in the US by Sense about Science USA, Dartmouth's Geisel School of Medicine and the Dartmouth Institute for Health Policy & Clinical Practice. [2]

Issues addressed

The project is a reaction to under-reporting of research. [3] [4] [5] [6]

A substantial proportion (estimates range from one-third to one-half) of medical research goes unpublished. [7] It has also been shown that negative findings are less likely to be published than positive ones, even in the absence of conflicts of interest.[ citation needed ]

Much medical research is done by the pharmaceutical industry, which have a conflict of interest reporting results which may hurt sales of their products. [8] There is a measurable funding bias in reporting; studies have shown that published drug studies funded by pharmaceutical companies are much more likely to support the use of the tested drug than studies with other funding. Industry-funded trials are also less likely to be published. [7] [9]

If the statistical methods used to analyse the trial are not chosen before the study it started, there is a danger that researchers will intentionally or unintentionally pick the method that gives the results they expect, or which gives the most significant results. This makes the analysis statistically invalid .

Not publishing trials which fail to find a clear effect exposes trial volunteers to pointless risk [10] and wastes research effort (as the same trial is repeated over and over). It also biases the medical literature, making it report effects where none exist (since, given enough trials, eventually one will find a difference by pure chance). [11]

Pre-trial registration makes non-publication and changes in analysis methods obvious to medical reviewers. It also enables authors of meta-studies to track down and analyse missing data. Finally, it lets doctors and patients know when a trial is looking for volunteers. [10]

There are other sources of bias, such as the conditions sometimes attached to funding by funding agencies with a financial interest in the trial's outcome. Medical researchers may be asked to agree to allow the funding agency to censor results. Some funding agencies may also refuse to give the medical researcher access to the raw data, giving them only the finished analysis, or even a draft paper, and asking them to put their name to it. This is not acceptable academic practice, and some academic journals require that authors sign a statement that they have not entered into such agreements. [8] [9]

Ben Goldacre, a physician and spokesperson for the campaign, would like to address the systematic flaws in clinical research which cause data to be lost after it is gathered. [12] [13] [14] [15] [16] [17] [18]

Coverage

The campaign has been widely covered, and supported, in the academic press. The British Medical Journal and PLOS are founding members. Nature [19] and The Lancet [20] both published supportive articles in January 2014.

There has also been mainstream media coverage. [21]

Controversy

There has been criticism from the Pharmaceutical Research and Manufacturers of America (PhRMA), with senior vice-president Matt Bennett saying that trial data disclosure measures which AllTrials has recommended to the European Medicines Agency "could risk patient privacy, lead to fewer clinical trials, and result in fewer new medicines to meet patient needs and improve health.". [22]

AllTrials have published a detailed statement [23] of exactly what they want to see published, which states "The AllTrials campaign is not calling for individual patient data to be made publicly available".

A 2012 editorial published by senior regulators from the European Medicines agency [24] largely agreed with AllTrials, saying "We consider it neither desirable nor realistic to maintain the status quo of limited availability of regulatory trials data". They were also of the opinion that adequate standards for protection of personal data could be written. However, they warned that third party reanalysis was neither a guarantee of quality nor of lack of conflict of interest, which, in the worst case, could lead to negative public health consequences.[ citation needed ]

They suggested that reanalyses should therefore be subject to the same regulations as sponsor analyses, such as registering analysis plans. They argued against completely unrestricted access to data, but in favor of broader access. [24] AllTrials is not calling for completely unrestricted access to raw data, [23] so the scope of disagreements is limited to what restrictions should be in place.

Supporters

The campaign is an initiative of Sense about Science, [25] Centre for Evidence Based Medicine, The Dartmouth Institute for Health Policy and Clinical Practice, [26] James Lind Alliance, Cochrane Collaboration, [27] [28] BMJ Group, PLOS, [29] and Bad Science. The petition statement of AllTrials has been signed by organizations including Wellcome Trust, [30] British Library, Medical Research Council (UK), British Heart Foundation, Institute for Quality and Efficiency in Health Care, National Institute for Health and Care Excellence, BioMed Central, [31] National Physicians Alliance, Royal Society of Medicine, Health Research Authority, American Medical Student Association, GlaxoSmithKline, [32] and others.

As of May 2017, The AllTrials petition has been signed by 90,282 people and 721 organisations. [33] In October 2016, AllTrials published a road map detailing steps that various types of organisations can take to get more trials registered and more results reported. [34]

85 investors with >€3.5 trillion (£2.45trn; $3.83trn) of investments have supported AllTrials (as of July 2015), with Peter van der Werf of RobecoSAM saying: "We deem this to be a financially material factor and encourage all companies to gain credibility regarding their approach to clinical trial transparency by signing up to the AllTrials principles.". [35] The Laura and John Arnold Foundation provided early and ongoing financial support. [36]

The original policy of the Coalition for Epidemic Preparedness Innovations required that funded parties pre-register any trials in a clinical trials registry, publish results within a year of study completion (except with compelling reason and permission of CEPI), publish results in open-access articles, and have mechanisms for securely sharing underlying data and results, including negative results, in a way that preserves trial volunteer privacy. In May 2018 the CEPI proposed changing the policy to remove these provisions. [37] The policy was changed by the CEPI in December 2018. [38] [39]

Opponents

The European Federation of Pharmaceutical Industries and Associations and Pharmaceutical Research and Manufacturers of America have expressed interest in lobbying against the campaign. [40] Campaign supporters criticized Hoffmann-La Roche's plans to be more open but not to the extent requested by AllTrials. [41] [42]

See also

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References

  1. ↑ "About". 1 December 2015.
  2. ↑ "All Trials Registered. All Results Reported". AllTrials. Retrieved 2015-11-17.
  3. ↑ Chalmers, I; Glasziou, P; Godlee, F (2013). "All trials must be registered and the results published" (PDF). BMJ. 346: f105. doi: 10.1136/bmj.f105 . PMID   23303893. S2CID   40236020.
  4. ↑ Bell, Alice (8 February 2013). "All Trials: working with the public to reform science". theguardian.com. Retrieved 26 October 2013.
  5. ↑ Glasziou, Paul (15 January 2013). "Register all trials, report all results – it's long overdue". The Conversation . Retrieved 26 October 2013.
  6. ↑ Cressey, Daniel (2013). "Secrets of trial data revealed". Nature. 502 (7470): 154–5. Bibcode:2013Natur.502..154C. doi: 10.1038/502154a . PMID   24108030.
  7. 1 2 Jones, C. W; Handler, L; Crowell, K. E; Keil, L. G; Weaver, M. A; Platts-Mills, T. F (2013). "Non-publication of large randomized clinical trials: Cross sectional analysis". BMJ. 347: f6104. doi:10.1136/bmj.f6104. PMC   3812466 . PMID   24169943.
  8. 1 2 Davidoff, F; Deangelis, C. D; Drazen, J. M; Nicholls, M. G; Hoey, J; Højgaard, L; Horton, R; Kotzin, S; Nylenna, M; Overbeke, A. J; Sox, H. C; Van Der Weyden, M. B; Wilkes, M. S (2001). "Sponsorship, Authorship, and Accountability". New England Journal of Medicine. 345 (11): 825–6, discussion 826–7. doi:10.1056/NEJMed010093. PMC   81460 . PMID   11556304.
  9. 1 2 Whoriskey, Peter (24 November 2012). "As drug industry's influence over research grows, so does the potential for bias" – via www.washingtonpost.com.
  10. 1 2 Dickersin, Kay; Rennie, D (2003). "Registering Clinical Trials". JAMA. 290 (4): 516–23. doi:10.1001/jama.290.4.516. PMID   12876095.
  11. ↑ Sterling, Theodore D (1959). "Publication Decisions and their Possible Effects on Inferences Drawn from Tests of Significance—or Vice Versa". Journal of the American Statistical Association. 54 (285): 30–4. doi:10.1080/01621459.1959.10501497. JSTOR   2282137.
  12. ↑ Fiore, Kristina (23 February 2013). "Is Evidence-Based Medicine Only an Illusion?". MedPage Today . Retrieved 26 October 2013.
  13. ↑ Buch, Prateek (10 January 2013). "Opinion: AllTrials.net – a crucial campaign on data transparency that will save lives". Liberal Democrat Voice . Retrieved 26 October 2013.
  14. ↑ Biome staff (20 May 2013). "Ben Goldacre on Clinical Trials". biomedcentral.com. Archived from the original on 2013-10-29. Retrieved 26 October 2013.
  15. ↑ Goldacre, Ben (1 February 2013). "Health Care's Trick Coin". The New York Times . New York. ISSN   0362-4331 . Retrieved 26 October 2013.
  16. ↑ Doyle, Kathryn (14 March 2013). "Surgery clinical trial results selectively reported". Chicago Tribune . Retrieved 26 October 2013.
  17. ↑ Olijnyk, Zena (22 Feb 2013). "Bad Pharma's bitter pill to swallow". m.bnn.ca. Business News Network . Retrieved 26 October 2013.
  18. ↑ Stugess, Kylie (27 February 2013). "Bad Pharma – Interview with Ben Goldacre". Skeptical Inquirer . Committee for Skeptical Inquiry . Retrieved 26 October 2013.
  19. ↑ "Data sharing will pay dividends". Nature. 505 (7482): 131. 2014. doi: 10.1038/505131a . PMID   24409508.
  20. ↑ Glasziou, Paul; Altman, Douglas G; Bossuyt, Patrick; Boutron, Isabelle; Clarke, Mike; Julious, Steven; Michie, Susan; Moher, David; Wager, Elizabeth (2014). "Reducing waste from incomplete or unusable reports of biomedical research". The Lancet. 383 (9913): 267–76. doi:10.1016/S0140-6736(13)62228-X. PMID   24411647. S2CID   28924552.
  21. ↑ The Editorial Board (4 July 2013). "Opinion - Full Disclosure Needed for Clinical Drug Data". The New York Times.
  22. ↑ Sample, Ian (21 July 2013). "Big pharma mobilising patients in battle over drugs trials data". the Guardian.
  23. 1 2 "All trials registered and results reported".
  24. 1 2 Eichler, Hans-Georg; Abadie, Eric; Breckenridge, Alasdair; Leufkens, Hubert; Rasi, Guido (2012). "Open Clinical Trial Data for All? A View from Regulators". PLOS Medicine. 9 (4): e1001202. doi:10.1371/journal.pmed.1001202. PMC   3323505 . PMID   22505851.
  25. ↑ Sense about Science (9 January 2013). "AllTrials campaign launch". senseaboutscience.org. Archived from the original on 2013-10-29. Retrieved 26 October 2013.
  26. ↑ "AllTrials campaign launched in US: Dartmouth's Geisel School of Medicine to lead the US campaign for all clinical trials to be registered and results reported". The Dartmouth Institute (Press release). 2013. Retrieved 26 October 2013.
  27. ↑ Cochrane Collaboration (2013). "Cochrane signs up to AllTrials initiative to campaign for registration and reporting of all clinical trials". cochrane.org. Retrieved 26 October 2013.
  28. ↑ Brown, Tracy (30 April 2013). "Editorial : It's time for AllTrials registered and reported". thecochranelibrary.com. Archived from the original on 29 October 2013. Retrieved 26 October 2013.
  29. ↑ Barbour, Virginia (18 January 2013). "Getting serious about registering and reporting trials". blogs.plos.org. Retrieved 26 October 2013.
  30. ↑ Wellcome Trust (16 September 2013). "House of Commons - Science and Technology Committee: Written evidence submitted by the Wellcome Trust". publications.parliament.uk. Retrieved 26 October 2013.
  31. ↑ BioMed Central (12 August 2013). "A Call to Action from AllTrials". blogs.biomedcentral.com. Archived from the original on 2013-10-29. Retrieved 26 October 2013.
  32. ↑ GlaxoSmithKline (5 February 2013). "GSK announces support for AllTrials campaign for clinical data transparency". gsk.com. Archived from the original on 2013-10-29. Retrieved 26 October 2013.
  33. ↑ "All Trials Registered. All Results Reported". AllTrials. Retrieved 2015-11-17.
  34. ↑ AllTrials campaign. 2017. Alltrials Roadmap http://www.alltrials.net/wp-content/uploads/2017/02/AllTrials-Roadmap.pdf
  35. ↑ Hawkes, Nigel (2015). "Investment managers back greater transparency of clinical trials". BMJ. 351: h4002. doi:10.1136/bmj.h4002. PMID   26207007. S2CID   38566459.
  36. ↑ Apple, Sam (January 22, 2017). "The Young Billionaire Behind the War on Bad Science". Wired.
  37. ↑ "MSF's response to CEPI's policy regarding equitable access". Médecins Sans Frontières Access Campaign.
  38. ↑ "Open letter to CEPI Board Members: Revise CEPI's access policy". Médecins Sans Frontières Access Campaign.
  39. ↑ Gerald Posner (2 March 2020). "Big Pharma May Pose an Obstacle to Vaccine Development". The New York Times . Retrieved 8 March 2020. Drug companies on CEPI's scientific advisory panel, including Johnson & Johnson, Pfizer, and Japan's Takeda, pushed back. CEPI mostly capitulated in a December 2018 two-page declaration in which it jettisoned specifics but gave lip service to its founding mission of "equitable access to these vaccines for affected populations during outbreaks."
  40. ↑ Sample, Ian (21 July 2013). "Big pharma mobilising patients in battle over drugs trials data". theguardian.com. Retrieved 26 October 2013.
  41. ↑ Hoffmann-La Roche (26 February 2013). "Roche launches new process for accessing clinical trial data". roche.com. Archived from the original on 2013-10-29. Retrieved 26 October 2013.
  42. ↑ Walsh, Fergus (26 February 2013). "Drug firm Roche pledges greater access to trials data". bbc.co.uk. Retrieved 26 October 2013.
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