Further Update

Hi AllTrials friends

Yesterday we sent our submission to the court in the judicial review brought against the HRA by Richmond Pharmacology.

We have spent the last few weeks ploughing through the hundreds of pages of documents. Richmond is currently asking the judge to rule that there is no overriding legal requirement to publicly register any trial. That’s not correct. Since 2011 all trials except for adult phase 1 have been publicly registered through the EU Clinical Trials Register. And by next year this legal requirement will extend to all clinical trials unless exempted according to some very tight criteria. Richmond is effectively asking the judge to set the clock back 10 years and wipe out the careful progress that has been made in relation to trials registration at national and EU level. We have set out in detail the legal frameworks related to this, and put forward legal arguments as to why HRA has a duty to monitor compliance with both legal requirements and sound practice for running a trial. However, Richmond has changed its case three times and may yet change it again.  

The hearing will be in open court in Manchester on Thursday 16^th July. We will be there. It would be lovely to see any of you who’d like to come along too; we could do with some help capturing what is discussed in Court. We are unlikely to know the result on the 16^th, we hope the Judge will make his decision by the end of July but it could be October.We and our barrister Jonathan Price and solicitor Robert Dougans knew that we faced a demanding timetable and it meant that two of us here at Sense About Science have been almost completely absorbed by reading and writing legal arguments (it’s why I don’t have a suntan, when most of London does!).

We have managed to keep the rest of the AllTrials campaign going only in the face of that because many of you have given us help and topped up our fundraising appeal. Thank you! In a couple of weeks I will be able to show you just how significant that is. We are about to break a story about a new group coming on board for all trials registered and all results reported, in a way that should change part of the international scene, for good. We are also reaching the critical mass to be able to launch a US campaign. I can see from the comments on the Just Giving site how determined you are that the challenge of the Richmond/HRA case is not going to stop this. And if you have been thinking about giving something, however small, could I urge you to do it now?  

Let us know if you can join us in court on 16^th.

Best wishes
Síle and James

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AllTrials vs Richmond Pharmacology

Dear AllTrials friend

We hoped to tell you more about the case Richmond Pharmacology is bringing against the HRA. That's not been straightforward. Richmond has now changed their argument three times and has altogether abandoned some arguments it relied upon earlier, so getting to grips with what is at stake has been difficult and time consuming for us and for our lawyers.

At the beginning of this week it looked as though Richmond had narrowed the case down to a technical argument about the wording of HRA’s guidelines which only applied for a period of 10 days earlier this year.

Just as the issues seemed to be narrowing, Richmond then asked the Court not to allow AllTrials to be heard. We had written to Richmond and the HRA outlining our planned argument to the court and inviting their response. HRA replied to us, Richmond did not. Instead they went straight to the Judge and asked him not to hear us.

And then yesterday we saw that Richmond has asked the Court at the very last minute to rule on something huge. They want the Court to declare that no trial sponsor or person running a trial has any legal requirement to publicly register any clinical trial unless the sponsor has given a legally binding commitment to do so, or an ethics committee has asked them to do so for every trial. So now the Court is being asked to rule not on the specifics of the case but on a much broader point.

Richmond has asked the Court for a hastily arranged hearing in Manchester on Monday where they will ask to seek that declaration as part of the case. This is after they have warned the court that AllTrials' references to international rules and protocols are irrelevant and will only add to their costs!

We need to be there on Monday to make it clear to the Court that it is being asked to rule on something that has real ramifications beyond this case. If Richmond win, this would go in the face of international laws, regulations, professional standards and the ethical rules of research. If such a declaration was made it would shatter the progress towards transparency made by AllTrials and the progress made internationally before AllTrials even started.

Today we are writing our submission to the Court to be allowed to speak on Monday. We’ll tell you more as soon as we know it. We have only been able to do this because hundreds of you have sent support, encouragement and donations. Thank you.

Best wishes
James

James Cockerill
Campaigns Manager

Sense About Science
Science and evidence in the hands of the public

Ben Goldacre writes in the BMJ - How medicine is broken, and how we can fix it

The chief medical officer’s review on statins and oseltamivir may look for answers in the wrong places

Last week there was extensive news coverage of a leaked letter written by the chief medical officer to the Academy of Medical Sciences. This letter focused especially on concerns around statins and oseltamivir (Tamiflu) and asked the academy for an “authoritative independent report looking at how society should judge the safety and efficacy of drugs.”1 The academy has since announced that it is convening a working group on the subject.

With any such report there are two major risks. The first is a focus on “trust” or even—as a worst case—false reassurance for well documented problems. We do not believe the academy will choose this path. But there is another, bigger risk: the academy may accept shortcomings in the evidence as somehow inevitable. Here there are good grounds for concern. The academy has already announced that its work “will explore how evidence that originates from different sources (e.g. randomised clinical trials and observational data) are used to make decisions about the safety and efficacy of drugs and medical interventions.”2

Focusing solely on existing trials and observational studies would represent a failure of vision and ambition in an era when medicine has both the need and the opportunity to innovate. Well documented problems exist in the funding and prioritisation of research, the conduct of trials, the withholding of results, the dissemination of evidence, and its implementation with patients. Here we briefly examine six domains where the academy could call for simple practical improvements that would address legitimate concerns.

Publication bias—We conduct trials to detect modest differences, and spend vast amounts of money specifically to exclude bias, yet we allow that bias to flood back in through selective publication.3 4 Eminent bodies writing reports will not fix this, but practical action will. We need new funding for simple systematic work to audit which trials are unreported, to highlight the best and worst performers, and to shine a light on withheld studies.5

Independent trials—A recent cohort study found that 97% of head to head trials sponsored by industry give results that favour the sponsor’s drug.6 Doctors and patients are right to want independent trials. On statins and oseltamivir, there are two clear opportunities, and here we declare our own conflicts. With colleagues, one of us (CH) first proposed a trial of oseltamivir in a pandemic in 2009; the other (BG) first proposed a trial of statins examining side effects over a year ago. In both cases we could have the answer by now.

Cost of trials—Replication will be possible only if the cost of conducting trials is radically reduced. Much of this cost is driven by disproportionate regulation around trials of routinely used treatments.7 The National Institute for Health and Care Excellence’s guidance on cholesterol argues for head to head trials in low risk populations; this would require over 100 000 participants, followed up for a decade. Such trials can practically be delivered only by reducing the expensive and disproportionate regulatory burden,7 embedding them in everyday clinical care and gathering follow-up data from existing electronic health records.8

Better evidence—Treatments are routinely approved after trials with only surrogate outcomes.9 Drugs are then extensively promoted, at the moment of approval, when evidence on real world outcomes is paradoxically at its weakest. We could encourage better evidence by, for example, compelling companies to follow-up all phase III trial participants until real world benefits emerge, considering routine randomisation for newly approved drugs when benefits are unclear, and bartering with either patent extension or choice of the start date for market exclusivity. These suggestions would come at minimal cost and deliver more comprehensive data on treatment effects.

Shared decision making—Concern over statins has recently been reawakened by the introduction of a financial incentive for general practitioners to prescribe the drugs to low risk patients. This is ill judged because patients’ informed choices vary widely.10 11 An incentive to prescribe a treatment that many adequately informed patients do not want undermines informed decision making and inflicts avoidable reputational harm on the profession. If instead we incentivise shared decision making then—for the same financial outlay—best practice will be recognised, rewarded, and laid down in the everyday templates of what doctors do.12

Declare conflicts of interest—Declaration of conflicts of interest is currently chaotic, inconsistent, and incomplete. We clearly need a central system of declarations, ideally maintained by the General Medical Council.13 Conflicts, however, become particularly salient when evidence is unclear: when decisions about which treatment works best are made on the basis of a speculative, superficially plausible narrative about a drug’s mechanism of action, or on the interpretation of weak, confounded, observational data when randomised trials are feasible. If we are able to generate better evidence and ensure that we see the complete evidence, then competing interests—although they must always be declared—will become less salient.

This is just a brief tour of six domains, and there is much more to be done. Most of our suggestions are rapidly deliverable. Some require modest funding; most do not. Some require legislative changes. But we should remember that evidence based medicine, in its true modern incarnation, has a relatively short history and that when randomised trials were first introduced they were often regarded as a transgressive, expensive, unnecessary, and unwelcome challenge to medical authority.14 The public is increasingly aware of the shortcomings we collectively tolerate in the evidence base for clinical practice. We now have the opportunity to use public frustration as fuel to update our implementation of evidence based medicine in the light of new technology and get our house in order. To restrict a review of these problems to the interpretation of inadequate existing data—as the academy apparently proposes—would be recklessly backward looking.

Notes
Cite this as: BMJ 2015;350:h3397

Footnotes
Competing interests: We have read and understood BMJ policy on declaration of interests and declare BG and CH are founders of the AllTrials campaign calling for all trials to report their results. BG receives funding from the Wellcome Trust and the Laura and John Arnold Foundation and income from speaking, writing, and broadcasting on problems in science and medicine. CH has received funding from a UK National Institute for Health Research grant (HTA—10/80/01 Update and amalgamation of two Cochrane reviews: neuraminidase inhibitors for preventing and treating influenza in healthy adults and children www.nets.nihr.ac.uk/projects/hta/108001). CH also receives occasional payments for running educational courses at the University of Oxford (see www.phc.ox.ac.uk/team/researchers/carl-heneghan for full details).

Provenance and peer review: Commissioned; not externally peer reviewed.

References
↵Wise J. England’s chief medical officer asks for review of drug evaluation in wake of statins controversy. BMJ2015;350:h3300.FREE Full Text
↵Academy of Medical Sciences. Academy launches new project on evaluating evidence. Press release, 16 Jun 2015. www.acmedsci.ac.uk/more/news/evaluating-evidence-launch/.
↵Schmucker C, Schell LK, Portalupi S, et al. Extent of non-publication in cohorts of studies approved by research ethics committees or included in trial registries. PLoS One2014;9:e114023.CrossRefMedline
↵Song F, Parekh S, Hooper L, et al. Dissemination and publication of research findings: an updated review of related biases. Health Technol Assess2010;14(8).iii, ix-xi,1-193.
↵Goldacre B. How to get all trials reported: audit, better data, and individual accountability. PLoS Med2015;12:e1001821.CrossRefMedline
↵Flacco ME, Manzoli L, Boccia S, et al. Head-to-head randomized trials are mostly industry sponsored and almost always favor the industry sponsor. J Clin Epidemiol2015;68:811-20.CrossRefMedline
↵Van Staa T-P, Dyson L, McCann G, et al. The opportunities and challenges of pragmatic point-of-care randomised trials using routinely collected electronic records: evaluations of two exemplar trials. Health Technol Assess2014;18:1-146.CrossRef
↵Van Staa T-P, Goldacre B, Gulliford M, et al. Pragmatic randomised trials using routine electronic health records: putting them to the test. BMJ2012;344:e55.FREE Full Text
↵Yudkin JS, Lipska KJ, Montori VM. The idolatry of the surrogate. BMJ2011;343:d7995.FREE Full Text
↵Fontana M, Asaria P, Moraldo M, et al. Patient-accessible tool for shared decision making in cardiovascular primary prevention: balancing longevity benefits against medication disutility. Circulation2014;129:2539-46.Abstract/FREE Full Text
↵Van Staa T-P, Smeeth L, Ng ES-W, Goldacre B, Gulliford M. The efficiency of cardiovascular risk assessment: do the right patients get statin treatment? Heart Br Card Soc2013;99:1597-602.Abstract/FREE Full Text
↵Goldacre B, Smeeth L. Mass treatment with statins. BMJ2014;349:g4745.FREE Full Text
↵McCartney M, Goldacre B, Chalmers I, et al. Why the GMC should set up a central registry of doctors’ competing interests. BMJ2014;348:g236.FREE Full Text
↵Blythe M, Cochrane A. One man’s medicine: an autobiography of Professor Archie Cochrane. BMJ Publishing, 1989.

Yes!

WHO calls for increased transparency in medical research

Note for the media
14 April 2015

14 APRIL | 2015 GENEVA - WHO today issued a public statement calling for the disclosure of results from clinical trials for medical products, whatever the result. The move aims to ensure that decisions related to the safety and efficacy of vaccines, drugs and medical devices for use by populations are supported by the best available evidence.

“Our intention is to promote the sharing of scientific knowledge in order to advance public health,” said Dr. Marie-Paule Kieny, WHO Assistant Director General for Health Systems and Innovation. “It underpins the principal goal of medical research: to serve the betterment of humanity.”

“Failure to publicly disclose trial results engenders misinformation, leading to skewed priorities for both R&D and public health interventions,” said Kieny. “It creates indirect costs for public and private entities, including patients themselves, who pay for suboptimal or harmful treatments.”

Unreported trials lead to misinformation

For example, in a study that analysed reporting from large clinical trials (more than 500 participants) registered on clinicaltrials.gov and completed by 2009, 23% had no results reported. These unreported trials included nearly 300 000 participants. Among clinical trials of vaccines against five diseases registered in a variety of databases between 2006-2012, only 29% had been published in a peer-reviewed journal by the WHO recommended deadline of 24 months following study completion.

“We need the collaboration of all these actors to enforce transparency in their jurisdictions in order to increase the benefits and decrease the risks for patients, clinical trial volunteers and the general public,” concluded Dr. Kieny.

International Clinical Trials Registry Platform furthers transparency

WHO’s call for disclosure includes older unreported clinical trials, the results of which may still have an important bearing on scientific research today. WHO also reaffirms the need for all clinical trials to be registered on a WHO primary clinical trial registry so that they can be accessible through the International Clinical Trials Registry platform. This will ensure transparency as to which clinical trials have occurred, and allow verification of compliance with public disclosure requirements.

The recent WHO move expands on a 2005 call for all clinical trials to be registered, and the subsequent establishment of the International Clinical Trials Registry Platform. This registry platform regularly imports trial records from Clinicaltrials.gov, ISRCTN, EU Clinical Trials Register, Australia New Zealand Clinical Trial Registry, Pan African Clinical Trial Registry and Clinical Trial Registries from China, India, Brazil, Republic of Korea, Cuba, Germany, Iran, Japan, Sri Lanka, The Netherlands and Thailand.

For more information please contact:

Tarik Jasarevic
Communications Officer
Mobile: +41 79 367 62 14
E-mail: jasarevict@who.int

Daniela Bagozzi
Senior Information Management Officer
Mobile: +41 79 603 72 81
E-mail: bagozzid@who.int

WHO Statement on Public Disclosure of Clinical Trial Results

• ICTRP: WHO Statement on Public Disclosure of Clinical Trial Results
  pdf, 278kb

Background

• Rationale for WHO's New Position Calling for Prompt Reporting and Public Disclosure of Interventional Clinical Trial Results
  PLoS Medicine
• WHO Policy on Open Access
• Public Health Research Data Forum

Following a ministerial summit on Health Research in 2004, a World Health Assembly Resolution passed in 2005 called for unambiguous identification of all interventional clinical trials. This led to the establishment of the WHO International Clinical Trials Registry Platform, which collates information on trials that have been notified in a network of clinical trial registries (who.int/ictrp/network). WHO’s existing position on registration is available at who.int/ictrp: “The registration of all interventional trials is a scientific, ethical and moral responsibility”. Deposition of information on trials in such registries, prior to their initiation, is a condition for publishing the results of trials in many leading medical journals. However, concerns have been raised that there may be selective publication of trials dependent on their results, with particular concern that trial results which may be viewed as “negative”, are less likely to be submitted, or accepted, for publication in the scientific literature or made public in other ways. Notification of trials to clinical trial registries has become more widespread, and it is possible to evaluate what proportions of recorded trials have not reported results at different times after the planned end dates of the trials. Multiple analyses have confirmed that a substantial number of clinical trials remain unreported several years after study completion, even in the case of large randomized clinical trials.

In the latest version of the Declaration of Helsinki it is stated that “Every research study involving human subjects must be registered in a publicly accessible database before recruitment of the first subject.” and that “Researchers have a duty to make publicly available the results of their research .... Negative and inconclusive as well as positive results must be published or otherwise made publicly available”. There is an ethical imperative to report the results of all clinical trials, including those of unreported trials conducted in the past. Furthermore poor allocation of resources for product development and financing of available interventions, and suboptimal regulatory and public health recommendations may occur where decisions are based on only a subset of all completed clinical trials.

Reiteration of WHO position on clinical trial registry sites

Before any clinical trial is initiated (at any Phase) its details are to be registered in a publicly available, free to access, searchable clinical trial registry complying with WHO’s international agreed standards. The clinical trial registry entry should be made before the first subject receives the first medical intervention in the trial.

Updating clinical trial registry entries

All clinical trial registry sites are to be updated as necessary to include final enrolment numbers achieved, and the date of actual study completion (defined as the last data collection timepoint for the last subject for the primary outcome measure). If clinical trials are terminated, their status is to be updated to note the termination, and to report the numbers enrolled up to the point of termination.

Reporting timeframes for clinical trials

Clinical trial results are to be reported according to the timeframes outlined below. Reporting is to occur in BOTH of the following two modalities.

1. The main findings of clinical trials are to be submitted for publication in a peer reviewed journal within 12 months of study completion and are to be published through an open access mechanism unless there is a specific reason why open access cannot be used, or otherwise made available publicly at most within 24 months of study completion.
2. In addition, the key outcomes are to be made publicly available within 12 months of study completion by posting to the results section of the primary clinical trial registry. Where a registry is used without a results database available, the results should be posted on a free-to-access, publicly available, searchable institutional website of the Regulatory Sponsor, Funder or Principal Investigator.

It is noted that several journals allow open access publication of clinical trial findings. Some journals have an explicit policy of supporting publication of negative trials. These 12 month and 24 month timeframes represent the longest possible acceptable timeframe for reporting and shorter timeframes are strongly encouraged. It should be possible in most instances for reporting to occur in shorter timeframes.

Reporting of past clinical trials results

Unreported clinical trials conducted in the past are to be disclosed in a publicly available, free to access, searchable clinical trial registry. In addition it is desirable that unreported clinical trials are published in a peer reviewed journal.

Inclusion of Trial ID in clinical trial publication

The Trial ID or registry identifier code/number is always to be included in all publications of clinical trials, and should be provided as part of the abstract to PubMed and other bibliographic search databases for easy linking of trial reports with clinical trial registry site records. Bibliographic search databases such as PubMed are encouraged to make Trial IDs easily available by inclusion in the abstract of each clinical trial record.

Note on Data Sharing Initiatives

The benefit of sharing research data and the facilitation of research through greater access to primary datasets is a principle which WHO sees as important. This statement is not directed towards sharing of primary data. However WHO is actively engaged with multiple initiatives related to data sharing, and supports sharing of health research datasets whenever appropriate. WHO will continue to engage with partners in support of an enabling environment to allow data sharing to maximise the value of health research data.

A day late - AbbVie drops legal action in EU drug secrecy case

LONDON, April 3 (Reuters) - AbbVie, one of the two U.S. companies trying to stop Europe's drugs regulator from releasing previously secret clinical trials data, said on Thursday it had withdrawn lawsuits against the watchdog.

The decision follows a move by the London-based European Medicines Agency (EMA) to accept a new set of redacted documents submitted by AbbVie, along with the company's rationale for removing certain commercially confidential information.

"A significant portion of data will be disclosed while protecting the information that is commercially sensitive," AbbVie said in a statement. "As a result, AbbVie has withdrawn its lawsuits."

The EMA said the "very limited redactions" would have no significant impact on the readability of the clinical study reports that were at the centre of the litigation.

The legal row between the EMA, AbbVie and a second drugmaker, InterMune, has thrown a spotlight on attempts by parts of the pharmaceutical industry keep its data secret, even as many doctors and campaigners demand greater transparency.

For AbbVie, the case was significant because the clinical trial data at stake related to its blockbuster rheumatoid arthritis treatment Humira, which is the world's top-selling prescription medicine.

Medical researchers and patient groups want access to detailed clinical trial data to improve third-party scrutiny of the drugs industry and to allow independent scientists to stress-test claims about drugs.

But many companies fear that complete disclosure of all information will damage their businesses and undermine the ability to defend patents.

The London-based watchdog has been on a collision course with much of the industry since pledging in 2010 to lift the lid on previously secret trial data submitted by companies as part of the application process for new medicines.

The scale of the data releases was to have been increased significantly this year under the EMA plans. But the process was stalled by the legal battle with AbbVie and InterMune.

The European consumer organisation BEUC, which was involved in the case as an official participant in favour of the EMA, said AbbVie's decision was a significant first step forward.

"It is our strong hope that InterMune, the other complainant, will follow suit," said Ilaria Passarani, head of BEUC's food and health department.

The EMA said the other court case brought by InterMune against the agency, challenging a decision to grant access to clinical-study reports, was ongoing.

AbbVie's decision to drop its lawsuits comes just one day after the European Parliament voted in favour of new legislation governing clinical trials that will force drug companies to be more transparent in releasing study results. (Reporting by Ben Hirschler and Kate Holton; Editing by Jane Merriman and Anthony Barker)

http://www.reuters.com/article/2014/04/03/europe-medicine-secrets-idUSL5N0MV54S20140403?rpc=401

Ben Goldacre writes in the BMJ

All trials should be registered, with their full methods and results reported, and routine audit on the extent of information withheld

The House of Commons Public Accounts Committee delivered a remarkable report on 3 January. Its initial remit was the United Kingdom’s £424m (€510m; $697m) stockpile of oseltamivir (Tamiflu), but the committee soon broadened out—with evident surprise—into the ongoing problem of clinical trial results being routinely and legally withheld from doctors, researchers, and patients.

This situation has persisted for too long. The first quantitative evidence on publication bias was published in 1986.1 Iain Chalmers described in 2006 how progress in the 1990s soon deteriorated into broken promises.2 Recent years have seen extensive denial. The Association of the British Pharmaceutical Industry (ABPI) has claimed that these problems are historic, and that results are now posted on clinicaltrials.gov. The recently defunct Ethical Standards in Health and Life Sciences Group,3 which most UK medical and academic professional bodies signed up to, falsely claimed that a “robust regulatory framework” ensures access to trial results.4 US legislation requiring all results to be posted on clinicaltrials.gov within 12 months of completion has been widely ignored,5 with no enforcement. There has also been covert activity from industry—a leaked memo on its “advocacy” strategy included “mobilising patient groups” to campaign against transparency.6

Despite this, we have achieved considerable progress. The AllTrials.net campaign, started 12 months ago, calls for all trials on all uses of all currently prescribed treatments to be registered, with their full methods and results reported.7 It now has the support of most medical and academic professional bodies as well as the National Institute for Health and Care Excellence (NICE), Medical Research Council, Wellcome, more than 130 patient groups, 60 000 members of the public, and many in industry including GlaxoSmithKline. The Health Research Authority has announced that registration will be a condition of ethics committee approval.8 The BMA has passed a motion stating that withholding trial results is research misconduct,9 and the General Medical Council is re-examining its guidance on the matter.

There have also been extensive new proposals for greater transparency from European Union legislators, the European Medicines Agency (EMA),10 and industry bodies.11 All, however, share the same loophole—they all propose improved access to information on trials conducted from 2014 onwards. This means that almost all trials relevant to current medical practice would be exempt (including, for example, those on oseltamivir).

We now have an unprecedented opportunity for change, with considerable support from medical and academic professional bodies, policy makers, patient groups, and—importantly—the public. It’s time to consider what practical improvements can be made.

Firstly, by whatever means necessary, the methods and results of all previous trials must be accessible to the medical and academic community, which produces the guidelines and systematic reviews that inform patient care. It is commonly assumed that it would be difficult to enforce demands for trial results from diffuse global organisations, but we have never tried simply asking in an organised fashion. For example, the EMA could ask all research organisations and companies with a marketing authorisation for full methods and results of all trials they have conducted, so that these can be posted online, on the first ever register of trials that aspires to be a complete record of all research. If this invitation is declined, we could be told.

Secondly, while the current state of secrecy continues, there is much to be done with the most basic research tool in medicine—audit. Industry is quibbling over the precise proportion of trials that go undisclosed. This should not be a matter of debate. We need a trials observatory, covering all trials on all currently used treatments, that matches registry entries and other sources of information on completed trials against sources of results, whether those are in academic papers, clinical study reports, regulatory documents, or online postings. From these data we could derive live dashboards on transparency to drive up best practice, identify the best and worst companies for missing results, the treatments where most information is missing, the best and worst investigators, and more.

This is actionable information. If routine audit shows a particular principal investigator is performing badly, with many unreported results, should ethics committees grant them access to more trial participants? Will patients participate in trials for companies that withhold results? If two treatments have equivalent benefits, but one comes from a company with a track record of transparency and the other from a company that actively undermines the transparency campaign, are those two treatments still equivalent, and which should a cautious clinician prescribe?

One aspect of the committee’s report was missed by popular commentators, but it exemplifies the peculiarity of the current situation. Professor Kent Woods, head of the Medicines and Healthcare Products Regulatory Agency (MHRA), told the committee that European regulators had everything on oseltamivir. Evidence from the Cochrane Collaboration seems to show that this is not true. Cochrane asked the EMA for all the documents it held on oseltamivir, under that agency’s contested new transparency policy, and the agency complied—on several trials it held incomplete information on the methods and results, and for many more trials, it held nothing.12 The Public Accounts Committee expressed concern, and Professor Woods may wish to clarify this matter. But it is odd that there is any uncertainty about what evidence exists, or what the MHRA, EMA, and NICE have seen, on currently prescribed treatments (www.bmj.com/tamiflu).

It is also remarkable that the medical community needs a committee of generalist politicians to reflect these problems back to us. We spend millions on individual trials to exclude bias and often to detect subtle differences between treatments, but we let those biases pour back in unnecessarily when we permit whole trials to be withheld. Future generations may look back at our present tolerance of withheld trial results in the same way that we look back on medieval blood letting.

Notes
Cite this as: BMJ 2014;448:g213

Footnotes
Competing interests: We have read and understood the BMJ Group policy on declaration of interests and declare the following interests: BG is involved in a project to audit missing trial results and receives income from speaking and writing for lay audiences on problems in medicine, including publication bias. CH has received grant funding from the National Institute for Health Research Health Technology Assessment Programme to review the evidence for oseltamivir (Tamiflu) and zanamivir (Relenza). BG and CH are cofounders of the AllTrials campaign.

Provenance and peer review: Commissioned; not externally peer reviewed.

References
↵Simes RJ. Publication bias: the case for an international registry of clinical trials. J Clin Oncol1986;4:1529-41.Abstract/FREE Full Text
↵Chalmers I. From optimism to disillusion about commitment to transparency in the medico-industrial complex. J R Soc Med2006;99:337-41. FREE Full Text
↵Arie S. How a marriage with big pharma ended in divorce. BMJ2013;347:f6062.FREE Full Text
↵Goldacre B, Carroll D, Hall E. Guidelines for collaboration with industry should be transparent. BMJ. 2013;347:f6100.FREE Full Text
↵Prayle AP, Hurley MN, Smyth AR. Compliance with mandatory reporting of clinical trial results on ClinicalTrials.gov: cross sectional study. BMJ. 2012;344:d7373.CrossRefMedline
↵Sample I. Big pharma mobilising patients in battle over drugs trials data. Guardian2013. www.theguardian.com/business/2013/jul/21/big-pharma-secret-drugs-trials.
↵AllTrials. What does all trials registered and reported mean? All Trials, 2013. www.alltrials.net/all-trials/.
↵Chalmers I. Health Research Authority’s great leap forward on UK trial registration. BMJ2013;347:f5776.FREE Full Text
↵BMA. Non-publication of trials results is research misconduct. http://ecancer.org/journal/news/4200-bma-----non-publication-of-trials-results-is-research-misconduct.php.
↵European Medicines Agency. Draft policy 70: Publication and access to clinical-trial data. 2013. www.ema.europa.eu/ema/doc_index.jsp?curl=pages/includes/document/document_detail.jsp?webContentId=WC500144730&murl=menus/document_library/document_library.jsp&mid=0b01ac058009a3dc.
↵European Federation of Pharmaceutical Industries and Associations/PhRMA. Principles for responsible clinical trial data sharing. 2013. www.phrma.org/sites/default/files/pdf/PhRMAPrinciplesForResponsibleClinicalTrialDataSharing.pdf.
↵House of Commons Committee of Public Accounts. Access to clinical trial information and the stockpiling of Tamiflu. 2014. www.publications.parliament.uk/pa/cm201314/cmselect/cmpubacc/295/295.pdf.

http://www.bmj.com/content/348/bmj.g213?ijkey=5aXoYcMGOETixKf&keytype=ref

Bergstroem's mobilising memo

Dear members and colleagues,

please find below a message from Richard Bergstroem , EFPIA DG with respect to the various elements of the Clinical Data sharing debate , the assignment of responsibilities (including work with US PhRMA colleagues) and next steps

A. Forthcoming industry commitment, incl advocacy:

The EFPIA Board has approved the draft position paper developed jointly by PhRMA and EFPIA. The final version is attached, and is now subject to confirmation by the PhRMA Board two weeks from now. PhRMA and EFPIA plan concomitant press releases in the week of July 22.

The advocacy plan, previously approved by the two Boards is underway, and follows four strands:

1. Mobilising patient groups to express concern about the risk to public health by non-scientific re-use of data.

2. Engaging with scientific associations to shape the industry commitment for data sharing, and to discuss concerns about re-use of data.

3. Work with other business sectors that are also concerned about release of trade secrets and commercially confidential data.

4. For the long-term, build a network of academics across Europe that has the capacity to counteract mis-use of data (that is deemed to be happen in any case).

 

There will be a series of meetings in Brussels, organised jointly by PhRMA and EFPIA, in the week of August 26 to advance these strands.

This work (commitment and advocacy) is coordinated by [Redacted], in close cooperation with PhRMA ([Redacted] and [Redacted]), with oversight by Richard Bergstroem and [Redacted], PhRMA.

B. EMA consultation on draft :

On June 24th , the EMA published its revised policy on the publication and access to clinical trial data for consultation. Comments are invited and should be provided to the EMA by 30 September 2013.

Whereas the press release was quite balanced, the detailed proposal raises concerns:

1. No process outlined to discuss CCI in CSRs prior to release.

2. Raw data: unenforceable controls to ensure robust and scientifically credible secondary analyses.

3. Requirement for anonymised raw data to be supplied at submission negates EMA’s responsibility for release of PP information.

4. Publication of CSRs from withdrawn or unsuccessful submissions could undermine future commercial viability of product.

5. Identification of study personnel.

The EMA document takes into consideration the outcome of the process run by the 5 CT advisory groups earlier in the year to which EFPIA contributed through the input prepared by the 5 Temporary Working groups (TWG) set up under the SRM PC auspices.

A detailed response will be prepared by a joint EFPIA-PhRMA team. The work will be led by [Redacted], Lilly, [Redacted]. From the EFPIA side the  EFPIA TWG chairs (Rules of engagement, Patient confidentiality, good analysis practice, CT data format, legal aspects) will be part of the drafting group:

[Names of four individuals within the drafting group redacted]

PhRMA will assign a small group of people from the bigger EMA data disclosure WG.

The drafting group will tentatively have a TC July 9.

The final draft will be shared for consultation with the broader membership later this month.

C: EFPIA-PhRMA intervention in the AbbVie case:

[Name], Pfizer, leads this work, in close cooperation with PhRMA and external legal counsel.

 

D: Clinical Trial Regulation:

Advocacy directed at Council (and EC and EP) will focus on:

- avoiding definitions of CCI in the CTR itself,

- seek to delete preamble text that CSRs do not "in general" include CCI (even if current text is acceptable as fall-back position).

 

The EFPIA PACT(Public Affairs on Clinical Trials) is responsible and will work closely with national associations and Brussels staff.

Regards,

[Redacted]

http://social.eyeforpharma.com/market-access/exclusive-guardian-memo-leak-richard-bergstrom