Clinical Trials - Science and Technology Committee Contents

4  Clinical trial transparency

The need for trial transparency

52. Clinical trials generate large amounts of information, much of which is used by regulators when evaluating a drug for licensing. The term clinical trial transparency generally refers to the extent to which this data is made more widely available, to other scientists, clinicians and members of the public.[178] Witnesses to our inquiry broadly supported the notion of greater trial transparency and pointed out that this would be likely to bring about a number of benefits, including:

  • Improved patient outcomes: several witnesses drew a connection between greater transparency and improved clinical decision-making—the AllTrials campaign[179] claimed that failures to register and publish trials led directly to "bad treatment decisions" and "missed opportunities for good medicine".[180] Dr Ben Goldacre, co-founder of the AllTrials campaign and a practising clinician and author, explained that "healthcare professionals and patients need the results of clinical trials to make informed choices about which treatment is best" and added that it was "not satisfactory to say that the results of trials should be reported only to regulators".[181] The Academy of Medical Sciences (AMS) agreed that if only a subset of clinical trials "with extreme, or favourable, results" reached the public domain, "a biased conclusion" could be drawn about a treatment's effectiveness, potentially leading to the wrong medical decisions being made.[182]
  • Enhanced scientific knowledge: according to the AMS, "greater access to appropriately controlled data for valid scientific inquiry offers significant scientific benefits and helps ensure scientific validity" by opening research up to greater scrutiny.[183] Tracey Brown, Managing Director of Sense about Science, agreed that this ability to "self-correct" is essential to science, explaining that:

    We do not have the modern scientific approach that we have today because everybody has secretly gone off and done things in the cupboard; we have it because people have tested each other's ideas, pulled them apart and asked if something could have been done better. That is a very important part of scientific medical advance.[184]

Sense about Science also stated that greater transparency could provide "a richer research base for both industry and academia" by increasing the visibility of research and thereby expanding the potential for collaboration and could also prevent the same trial from being unknowingly conducted more than once.[185]

  • Increased public trust in research: it was a common view that greater transparency of trial data would engender greater public trust in medical research. Dr Margaret McCartney, a General Practitioner and medical writer, told us that lack of transparency in the past meant that she could currently "have no faith that patients taking part in clinical trials are not doing themselves harm".[186] INVOLVE, the national advisory group for public involvement in research, agreed that there needed to be "far greater openness and transparency in the publishing and accessibility of research findings" if the public were to "trust and have confidence" in clinical trials.[187]
  • Fulfilment of basic ethical standards: several witnesses felt that it was unethical not to make the results of clinical trials public. A group from the Cochrane Collaboration, an independent research organisation, stated that for "experiments conducted on human beings" the full reporting of results "should be a right, not a gift".[188] Dr Goldacre agreed, telling us that by failing to make trial data transparent researchers were "breaching the ethical pacts" forged with patients when they agreed to take part in a clinical trial.[189] A letter from 53 trial participants to the European Medicines Agency (EMA), provided to us by Sense about Science, stated that failure to publish the results of clinical trials was "a betrayal of our trust in clinical trial regulation, and the trust of the families of those patients who volunteer for trials having had a terminal diagnosis".[190]

53. While support for the notion of greater trial transparency was strong, witnesses acknowledged that there were challenges, including the need to:

  • protect the privacy of patients participating in clinical trials and ensure that data disclosure did not go beyond the confines of patient consent;
  • protect any intellectual property contained within clinical trial data and respect commercial sensitivities, and
  • mitigate the risk that clinical trial data would be re-analysed in an inexpert or irresponsible way, potentially leading to regulatory decisions being undermined and misleading conclusions reaching the public domain.

54. The most significant of these concerns related to patient privacy. Clinical trials can use and generate a large quantity of personal data, many of which could serve in combination to identify the patient even if their name were removed (for example, the patient's age, weight, occupation, the condition that is being treated and the location of their local hospital). While the disclosure policies currently applied by most pharmaceutical companies may limit trial transparency, according to the Association of the British Pharmaceutical Industry (ABPI) they also "protect patients' personal data" as "consent is not given for [patients'] data to be utilised by other third parties".[191] Roche also noted that "many of the trials of today's medicines were conducted many years ago when the imperative for transparency of patient-level data was somewhat less" and, as a result, "they were not always conducted in a way which supported easy disclosure of patient-level data".[192] In particular, according to Roche, in many cases "the wording of the patient consent forms" from past trials makes data-sharing "very difficult to achieve".[193] The ABPI, BioIndustry Association (BIA) and others also emphasised the need to protect commercial interests.[194] The BIA argued that regard must be given to the "considerable investment in intellectual effort, inventive skill, time and money" represented by a clinical trial, which could be put at risk if "trade secrets" were revealed through a requirement for increased data disclosure.[195] The concern that making trial data more widely available would make it vulnerable to inappropriate re-analysis was also widespread.[196] Sir John Bell, Regius Professor of Medicine at the University of Oxford and a non-executive Director of several life science companies, described the threat as follows:

    Large trial analysis can be done using multiple tools and, by parsing the data in a variety of ways, many different conclusions can be drawn. The public and the press are ill-equipped to deal with such assertions and it can take many years before the effects of such analyses are corrected.[197]

Dr Keith Bragman, President of the Faculty of Pharmaceutical Medicine (FPM), agreed, arguing that "simply to open up these data resources to anybody, and for them to do anything that they wish and perhaps come up with claims that cannot be substantiated, could create a chaotic situation".[198]

55. Others, however, disputed the significance of each of these challenges. Dr Goldacre, for example, while acknowledging that there were "challenges in ensuring confidentiality for individual patients", felt that these challenges could "be overcome", and Sense about Science pointed out that many forms of trial data did not include individual patient-level information and suggested that, where they did, such data could be redacted.[199] There was also disagreement about the extent to which trial data should be treated as commercially confidential, with the BMJ asserting that many data did not include commercially sensitive information and arguing that, even where it did, "citizens' right to know should override commercial confidentiality".[200] Sir John's argument that the public was "ill-equipped" to deal with the conclusions drawn from secondary analysis was disputed by Dr Helen Jamison of the Science Media Centre, who argued that the mainstream media was now more able to deal responsibly with medical "scare stories" than it was in the past, making it less likely that misleading and potentially harmful analyses would reach the public domain.[201] These arguments are considered further later in the Report.[202]

56. In bringing about greater transparency, several witnesses also emphasised the need to extend policies to trials that had occurred in the past, as well as those that will occur in the future.[203] In Dr Goldacre's words, since most of the drugs currently in use came onto the market as a result of trials conducted several years ago, efforts focused only on future trials will "do nothing to improve medicine until most of us are dead".[204] While acknowledging these calls for retrospective action, the AMS nevertheless considered that "the focus should be on developing mechanisms to ensure rapid prospective posting and publication of current and future trials as this can be practically addressed more swiftly".[205] It cautioned that resources, in particular, "could be a key constraint" when considering retrospective disclosure.[206]

57. It is not enough simply to release data; Professor Peter Johnson, Chief Clinician at Cancer Research UK, explained that greater transparency would be of limited value if it resulted in scientists and the public being "simply swamped in largely meaningless" information.[207] According to the Royal Society, in order to avoid this scenario and realise the benefits of open scientific data, data must be:

  • accessible and readily located;
  • intelligible to those who wish to scrutinise them;
  • assessable so that judgments can be made about their reliability and the competence of those who created them; and
  • usable by others.[208]

The AMS agreed that information from clinical trials should be shared in a way that was "intelligible, assessable, reliable and usable" and Ms Brown also considered that an "intelligent approach" to data sharing was needed, adding that "we do not want a situation where [...] people put things into the public domain in binary code [for example], or where there is data dumping".[209]

58. Clinical trial transparency is important and greater transparency would be likely to provide a number of benefits, particularly if applied retrospectively. However, there are obstacles to achieving this and the drive for greater transparency must be balanced against other concerns, particularly the need to protect patient privacy. Greater disclosure does not necessarily equate to greater transparency if the information shared cannot easily be understood and we therefore recommend that efforts to increase the availability of clinical trial data focus on providing information that is accessible, assessable, intelligible and usable.

The four levels of clinical trial transparency

59. The costs and benefits of making clinical trials more transparent are closely linked to the types of information being discussed, which can range from high-level facts about the aims and planned methods of a trial, to the thousands of lines of raw data generated over its course. The AMS explained that "clarity about which aspect of transparency" was being discussed was important, "as each presents different issues" which could significantly affect the arguments for and against making a particular level of trial data more transparent.[210] We agree and have therefore differentiated between four levels of trial transparency in drawing our conclusions. These are:

  • trial registration (level 1): a record that the trial has been conducted, from a clinical trial register detailing basic trial information;
  • summary-level trial results (level 2): a brief summary of the trial's results, together with key conclusions, most commonly in an academic journal or trial register;
  • clinical study report (level 3): a detailed report, usually prepared for regulatory purposes, of the method, conduct and outcome of a trial, often running to several hundred pages in length; and
  • individual patient-level data (level 4): the raw patient data generated over the course of a trial, from which aggregate results and other conclusions are drawn.


60. A registered trial is one whose details have been entered onto a publicly-accessible database in advance of its commencement. There are many trial registries currently in existence but, as of mid-2013, only 15 were recognised as "primary registries" by the World Health Organisation (WHO).[211] To be listed as a primary registry, registers must include details of:

  • the trial sponsor and source of funding;
  • countries of recruitment;
  • a description of the intervention being tested;
  • key inclusion and exclusion criteria for trial participants;
  • target sample size (the number of participants the trial intends to enrol), and
  • the outcomes that the trial is intended to test.[212]

Current WHO primary registries include several national trial registries, the EU Clinical Trials Register[213] and, a global database that accepts registration of any study designed to assess the efficacy of a health intervention in a human population.[214]

61. Witnesses were unanimous in their support of trial registration. The Wellcome Trust stated that registration was "the most important" way in which clinical trials could be made more open to scrutiny, while Dr Fiona Godlee, editor-in-chief of the British Medical Journal (BMJ), claimed to "only see benefits", explaining that "if prospective trial registration were working [...], it would ensure that we would have a full record of all the ongoing trials and, therefore, the potential to chase up and obtain the full results of those trials".[215] Tracey Brown, Sense about Science, agreed that, at present:

    We do not even have the contents list, if you like, of what has been done, never mind being able to track down some of the results. That is something that reviewers who are looking across a whole range of studies really struggle with; they spend a lot of time just trying to find out what has actually been done but been left in a cupboard somewhere. Registration is about knowing what the trial is for and registering the protocols.[216]

Dr Elizabeth Wager, a freelance writer and publications consultant, noted the particular importance of registering design details before a study began, in order to "help to reduce, or at least identify, the selective reporting of outcomes, or changes in study design occurring between initiation and publication".[217]

62. Although several attempts have been made to increase the level of trial registration,[218] evidence suggests that many trials remain unregistered. According to Dr Goldacre, a 2009 study found that "half of all trials published in major medical journals [...] had not been properly registered, and a quarter had not been registered at all".[219] In the UK, a 2013 sample audit conducted by the Medical Research Council (MRC) also found that a significant proportion of MRC-funded trials—14%—had not been registered, even though this was a condition of the grant.[220] The Minister, however, while agreeing that all trials should be registered "whatever their nature", appeared to believe that there was currently "no problem" with this aspect of transparency since a number of publicly-accessible registers were already in existence.[221]

63. We consider universal trial registration to be a crucial step in increasing clinical trial transparency and believe that all future trials should be included in a publicly-accessible register. This is clearly not the case at present, even for trials conducted in the UK. We recommend that the Government take steps to ensure that, in future, all clinical trials conducted in the UK, and all trials related to treatments used by the NHS, are registered in a WHO-listed primary registry.

64. Since the trials of treatments currently in use often occurred many years ago, retrospective disclosure is important if the benefits of clinical trial transparency are to be realised in the short to medium-term. Although retrospective trial registration will incur some cost, we consider that this will be outweighed by the public health benefit of having a complete picture of the trials conducted on treatments currently available to patients. The Government should support the retrospective registration of all trials conducted on treatments currently available through the NHS and should actively pursue policies to bring this about.


65. The term "summary-level trial results" refers to the relatively basic information needed to understand the outcome and potential implications of a clinical trial. Such information is most often found in a scientific journal but can also be included in a variety of other media, such as trial registers, sponsor websites, regulatory documents and conference posters and presentations. Although summary-level results can come in many forms, there are some common standards, and such summaries usually include an exposition of the aims, methods, results and statistical findings of a trial.[222]

66. Most of those who submitted evidence to our inquiry agreed that summary-level results should be published for all trials, and the Government also stated that it was "fully supportive of transparency in the publication of clinical trial results".[223] However, there was some debate over the most appropriate mode of publication for this type of data. The AMS recommended the use of "peer-reviewed media such as scientific journals", as did the Cochrane Collaboration's meta-analysis methods group, which stated that formal publishing would be "preferable" to alternative models "because of the more permanent nature of journals and [the] advantage of peer review".[224] Dr Wager agreed that publication in the peer-reviewed literature had many benefits, including "permanence, the possibility for corrections or retractions, some measure of quality control via peer review, [and] the opportunity for post-publication commentary and discussion".[225] In 2011, we reached a similar conclusion in our Report on Peer review in scientific publications- which stated that "peer review in scholarly publishing, in one form or another, is crucial to the reputation and reliability of scientific research".[226]

67. However, there are several limitations to academic journals as a source of summary-level trial results, the most significant of which, according to the advocacy groups Healthy Skepticism UK (HS-UK) and Health Action International (HAI), is the potential for journal articles to "not only misrepresent the actual results or conclusions of that study but also skew the larger body of evidence".[227] HS-UK and HAI stated that misrepresentation could come in the form of several types of reporting bias, which affect how, when and where a trial is published, based on the nature and direction of its results.[228] The most frequently highlighted bias was publication bias, whereby "positive" results—those which suggest that a treatment is effective—are placed in the public domain more frequently than "negative" results. Dr Wager, an ex-employee of the pharmaceutical industry, agreed that "under-reporting" was a problem, particularly for negative results, and put this down to a number of causes including:

  • clinical investigators being uninterested in unexciting or unfavourable results;
  • journal space constraints and the rejection of papers detailing "negative" results;
  • deliberate omission of unfavourable or inexplicable outcomes; and
  • resources being transferred away from drugs that were no longer being developed, making publication of the results of related trials a low priority.[229]

The Global Alliance of Publication Professionals (GAPP) agreed with Dr Wager that "publications do not write themselves" and suggested that many studies remained unpublished simply because researchers "lack the resources to write up their results".[230] Dr Godlee, BMJ, however, criticised researchers who kept trial results "in their bottom drawer" if they did not "come up with the results that they wish[ed] for".[231] Dr Godlee agreed that in the past journals had also been at fault in failing to publish "negative" results, but claimed that the introduction of "open access journals and online journals that have lots of space to publish negative and neutral results" meant that this was no longer the case.[232] BioMed Central, an academic publisher, concurred, suggesting that rejection by journals was no longer a valid reason for non-publication since "many peer-reviewed journals [...] strongly encourage publication of negative results" and "at least one journal makes publication of negative results its mission": the Journal of Negative Results in Biomedicine.[233]

68. We consider that summary-level results should be made publicly available for all clinical trials and we welcome the many new media through which it is now possible to share this information. Nevertheless, peer review is vital to the reputation and reliability of scientific research and we deem it appropriate that journal articles remain the primary instrument for the publication of summary-level trial results.

69. Many historic trials remain unpublished, which is far from ideal. However, retrospective publication of all trials of all treatments currently in use, while desirable, would almost certainly be unachievable given the likely time and resources that this would require. We therefore emphasise again the importance of retrospective trial registration as a means of providing a vital "index" against which individual cases of non-publication can be identified and, where of particular importance, pursued on an ad hoc basis.

70. Given recent changes to academic publication models, we do not recognise as legitimate the argument that it is not possible to publish "negative" results in a peer-reviewed journal and we consider failure to publish on a timely basis to be poor scientific practice. However, we are sympathetic to the pressure that scientists are often working under and therefore we urge the Government and other trial funders to ensure that researchers are provided with the time and resources needed to meet their publication obligations.

71. In 1981, Franz Ingelfinger, editor of the New England Journal of Medicine (NEJM) stated that, in future, the NEJM would only accept papers on the understanding that "neither the substance of the article nor any of its pictures or tables have been published or will be submitted for publication elsewhere".[234] Many other medical journals followed suit, applying the "Ingelfinger Rule" to their own publications, with the result, according to Dr Wager, that "if a company wishes to publish an article in a medical journal it will be deterred from posting a study report or extended summary on a website".[235] CR-UK demonstrated the ongoing impact of the Ingelfinger rule, stating that in some cases, if trial results were due to be published in an academic journal, it could not add results to its own CancerHelp UK database until the publication date had passed.[236]

72. We encourage academic publishers to remove "Ingelfinger" restrictions on the pre-publication of summary-level results through media such as trial registries, in order to facilitate greater openness and faster access to important scientific data.


73. A clinical study report (CSR) is a standardised account of the plan, conduct and outcome of a clinical trial. A CSR includes significantly more detail than summary-level trial results and contains in its appendices large amounts of information not usually found elsewhere, such as patient data listings, names and CVs of the investigators involved in a trial, documentation of statistical methods and case report forms.[237] The standard CSR format was designed by an international collaboration in 1995,[238] in the hope that "the compilation of a single core clinical study report acceptable to all regulatory authorities" would ease the burden on sponsors hoping to gain approval for a new product in multiple jurisdictions.[239] Today, CSRs—often running to several hundred pages in length—are primarily used as regulatory documents and are not generally prepared for non-commercial trials.[240]

74. We heard mixed evidence about the importance of CSRs and whether or not they should be placed in the public domain. According to GAPP, "making [CSRs] available would do considerably more for transparency than any attempt to increase rates of publication in peer-reviewed journals" because the level of detail included in a CSR "far exceeds" that of an academic paper.[241] The Cochrane Collaboration agreed that, while CSRs were "massively complex documents, containing hundreds or thousands of pages of information with minute details about trials, their planning and execution", they were nevertheless an important source of additional data because they allowed for scrutiny of what had been published about a trial in the academic literature.[242] Dr Goldacre drew on the example of Roche's drug Tamiflu to highlight this point:

    By comparing clinical study reports on Tamiflu against brief published reports, Cochrane has already found discrepancies. For example, things that were described as placebos in the academic journal article turned out to be, first, a different colour from the active treatment, and, secondly, not to be inert placebos at all; in fact they had active ingredients. [...] It is to resolve discrepancies like that that we need better access to clinical study reports.[243]

In light of their potential value, Oxford University's Centre for Evidence-based Medicine proposed that legislation be introduced "to make clinical study reports, of all completed trials, available within one year of trial completion".[244] Sense about Science's AllTrials campaign made a similar call for "the publication of the results (that is, full clinical study reports) from all clinical trials—past, present and future—on all treatments currently being used".[245]

75. In contrast, many other witnesses stressed the relative unimportance of CSRs when compared with other forms of disclosure, such as trial registration and the publication of summary-level results. When asked whether he would be in favour of publishing CSRs for all trials, Professor Sir Michael Rawlins, AMS, told us that he was "ambivalent" about whether it was worth publishing them, explaining that were "voluminous", sometimes running "to thousands of pages" and did not "add very much".[246] Professor Johnson, CR-UK, agreed that it was "important to dispel any misconception" about how useful a CSR was "in its unedited and unanalysed form", and warned us of the "opportunity cost" that would be associated with preparing them for non-commercial trials, telling us that "doing more trials and doing them faster" represented better use of limited resources.[247] Other non-commercial trial sponsors agreed that a "huge additional financial and time burden" would be introduced if they were to start producing CSRs, as was being discussed at EU-level as part of the revision of the Clinical Trials Directive in early 2013.[248] The MRC stated that mandatory CSR production for non-commercial trials would introduce "a significant burden on academic funders" with each CSR taking "about three months' additional work to produce".[249]

76. Even for commercial trials, for which CSRs are already produced as standard, there are potential problems associated with greater transparency. There were mixed views on whether or not CSRs contained commercially sensitive information, the disclosure of which could potentially harm industry. According to the ABPI:

    As clinical study reports, until now, have been written for a regulatory audience and assuming confidentiality, they may describe commercial plans of the company. For instance, the development strategy for future studies on new indications may be described to put the particular study in context. [...] Furthermore, study reports often include appendices with detailed information on analytical methods (chemical and physical) and on the manufacturing of the clinical trials material.[250]

Disputing this, however, Dr Goldacre pointed out that the European Medicines Agency (EMA) had already shared some of the CSRs that it held, suggesting that this information was not commercially sensitive.[251] According to the BMJ, the European ombudsman had also declared that there was "no commercially confidential information" in a CSR.[252]

77. There was greater consensus over the legitimacy of the issue of patient confidentiality, although there remained disagreement over how easy this might be to resolve. Sir Kent Woods, then Chief Executive of the MHRA and Chair of the EMA's Management Board, told us that "to ensure that one is not releasing personal, identifiable data", CSRs "need to be quite carefully scrutinised before release and may need to be redacted in places; and that is a very labour-intensive process".[253] He explained that the EMA had released 1.6 million pages of clinical trial data over two years, and that this had cost it "somewhere between €2 million and €3 million".[254] Dr Goldacre disputed this point, claiming that it was "easy to redact" patient confidential information from CSRs and that the European Ombudsman had agreed that "the administrative burden" of preparing CSRs for publication was "not significant".[255] Dr James Shannon, GSK's Chief Medical Officer, also believed that it could be "very difficult" to redact patient data included in historical CSRs because this information is "on paper" rather than in electronic databases.[256] Nevertheless, in February 2013, GSK committed to posting CSRs on its own dedicated clinical trials register for all approved medicines dating back to the company's formation in 2000, suggesting that while potentially difficult, comprehensive publication of redacted CSRs was not impossible.[257] (This and other industry-led initiatives to increase trial transparency are discussed later in the Report).

78. The Minister commended GSK for its "good work" in this area, although he stated that the Government considered "publication of summaries" rather than CSRs to represent "the right level" of trial transparency.[258] The Minister added that he considered it "unduly burdensome" to require publication of "a fully fledged CSR" for all trials, and told us that the Government had been "concerned" about EU discussions earlier in the year which had suggested that CSR preparation might become mandatory for all trials as part of the revised Clinical Trials Regulation.[259] Following further discussion, however, the current draft Regulation does not include this requirement.[260]

79. It would be unduly burdensome to mandate that clinical study reports (CSRs) be produced for non-commercial trials. We also consider that issues concerning the reliability of the information contained in academic journal articles should be dealt with at source, for example by strengthening the peer review process as recommended in our 2011 Report, rather than by effectively bypassing academic publication through greater reliance on CSRs. We therefore do not support any move to make it mandatory for non-commercial trials to produce a CSR, or any other document of an equivalent level of detail. However, we recognise that CSRs can provide a useful contribution to the scientific literature and, once a regulatory decision has been reached, we see no compelling reason why CSRs should not be placed in the public domain, with identifiable patient data redacted.


80. Individual patient-level data (IPD) are the underlying data collected from patients participating in a clinical trial. For example, IPD from a trial of a new diabetes drug might include details of a participant's changing blood sugar levels over time, together with their age, gender, height, weight, dates and locations of hospital visits, and various other pieces of personal, clinical and administrative information.

81. At present, public disclosure of IDP is not mandatory for any type of trial, and the European Medicines Agency (EMA) does not regularly request access to IPD for the trials that it evaluates, unlike the US Food and Drug Administration (FDA).[261] However, several witnesses emphasised the potential scientific value of this data and advocated greater access to it. For example, the data-sharing company PatientsLikeMe considered that "society would benefit significantly" from the transition of trial results from "inaccessible records" to "an open repository of machine-readable data" and several witnesses pointed out the potential for such data to be reanalysed and combined to produce much more reliable and statistically significant results.[262] As a result, Michael Power, a clinical researcher, recommended that the Government commit to making all trial data, suitably anonymised, "publicly and freely available on the internet without unreasonable delay".[263] In an effort to increase the transparency of IPD, in January 2013 the BMJ announced that it would "no longer publish any trials of drugs or devices where the authors do not commit to making the relevant anonymised patient-level data available upon reasonable request".[264] In contrast, Professor Sir John Bell believed that "the extreme position of making all patient line data available to all comers" had not been "properly thought through", adding that, "if applied forcefully for early stage trials", such as position would "essentially eliminate the biotechnology sector in the UK".[265] He, and several other witnesses, cited three issues in particular in opening IPD up to wider scrutiny: the potential detrimental effect on industry, the risk of inappropriate reanalysis and reinterpretation of data, and the need to protect patient confidentiality.

82. In considering the costs and benefits of sharing IPD, the ABPI stressed the need to protect the "legitimate interests of companies".[266] Dr James Shannon, Chief Medical Officer of GSK, also acknowledged that "if companies make [individual patient-level] data available, other companies will access it", describing how, during four hours in which GSK's new IPD-sharing system prematurely went live by accident, "three other companies accessed the data, plus Johns Hopkins hospital in the United States", despite there being no announcement of the system's activation or guidance in accessing it.[267] However, Dr Shannon considered that "the more eyes that are put on data the better, and that is why GSK has taken the lead to commit both to patient level data transparency as well as clinical study reports".[268]

83. On the topic of inappropriate reanalysis and reinterpretation of IPD, the co-convenors of the Cochrane Collaboration IPD meta-analysis methods group told us that:

    Our experience of obtaining IPD directly from those responsible for trials has highlighted the difficulty of understanding datasets at face value. A detailed dialogue with the trial investigators is often required to reach a full understanding of the trial and its data. This understanding is necessary to avoid inappropriate or naive analyses.[269]

The Ethical Medicines Industry Group, a trade body representing small and medium-sized biopharmaceutical companies, warned that "sub-optimal analyses" could "only inevitably lead to sub-optimal conclusions and sometimes these will be dangerous to public health", and Dr Jamison, SMC, agreed that there was "a risk that, if there is more information out there, there is an opportunity for groups and individuals to either misuse that information or for groups who have an agenda to seize on it". [270] Roche cited "the scares around MMR vaccines" as an example that highlighted "the importance of handling data in a responsible way".[271] However, Dr Jamison questioned whether this was a valid comparison, stating that she did not think that we were "in the situation that we were in when we had the MMR scandal in the 1990s", and pointing out that "if you do not put that data out there, it may equally lead to scare stories, mistrust and confusion".[272]

84. The most substantial barrier to the sharing of IPD is the risk that it would violate patient privacy. IPD contains large amounts of personal information, and although anonymisation can reduce the risk of trial participants being identified from their data, several witnesses pointed out that this risk could not be entirely eliminated.[273] William Burns, a Roche Board Member, told us that patient confidentiality was a particular issue for trials of rare ("orphan") diseases, and other trials involving small numbers of participants, since this made it "more difficult" to effectively anonymise patients.[274] For example:

    If you had cystic fibrosis but you give a postcode, there may be only one child in that postcode that has the disease. As you get down to the more orphan diseases, it needs a little more thoughtfulness about how to protect the interests of the patient.[275]

The Cochrane IPD meta-analysis methods group agreed that relying on anonymisation of IPD "would retain some risk of disclosure" and told us that this would also "render the data less useful for research purposes" because of the information necessarily removed in the process of anonymisation (for example, the conversion of dates of birth into age brackets, or the removal of information such as a participant's occupation).[276]

85. In March 2013, the Department of Health published a review looking at the balance between sharing personal information and protecting individuals' confidentiality. The Information Governance Review, led by Dame Fiona Caldicott—known as the Caldicott 2 Review—concluded that:

    while from a legal perspective, patient data exists in one of two forms—with patients either identified or anonymous, in reality, the situation is more complex. In particular, there is a 'grey area' of data that on its own does not identify individuals, but could potentially do so if it were to be linked to other information".[277]

Peter Knight, Deputy Director, Head of Research Information and Intelligence at the Department of Health, told us that the IPD generated from a clinical trial was likely to fall into this "grey area", for which anonymisation was "a starting point" but where there remained a risk that participants could be re-identified by "meshing [...] together" other datasets in the public domain.[278] The Caldicott 2 Review recommended that for such data there should always be "safeguards for limited access" comprised of two components, "a contractual agreement and a set of data stewardship functions", recommending that such data could be managed through secure environments known as safe havens.[279]

86. Dr Godlee considered that an alternative solution would be to simply obtain a patient's consent to share their data at the outset.[280] Mr Denegri, NIHR and INVOLVE, agreed that patient consent could provide part of the solution, explaining that:

    There will always be some people who are concerned about [making their data available], and some quite rightly because they have a stigmatised disease and have a life experience that is extremely arduous. But, generally speaking, if you enter into a dialogue with a group of patients, they readily get the idea about data and why data need to be shared, or why it is beneficial to do so, and they will readily buy into that, as long as the rules are clear, the risks are clear and they know where they can get further information.[281]

CR-UK pointed out, however, that when it comes to retrospective disclosure of IPD, lack of patient consent may be a more difficult problem to overcome, since "patients may have only provided consent for their data to be used in a certain way", which prevents it from being shared with other researchers, for example.[282] A possible solution to this problem would be to contact patients again retrospectively to request consent. However, Professor Karol Sikora, Medical Director of Cancer Partners UK and Dean of the University of Buckingham Medical School, told us that this would be a difficult exercise and one that might "rekindle unpleasant memories" for patients and their families, particularly if the trial had not been a success.[283]

87. Serious reservations were expressed about increasing the transparency of IPD. For example, Sir Michael Rawlins, AMS, questioned how useful this type of data would be to "anybody who was not an expert statistician" and even the Cochrane Collaboration's IPD meta-analysis methods group—a group dedicated to providing guidance to those wishing to use IPD—stated that it would "not support open public access to clinical trial IPD".[284] David Willetts, Minister for Universities and Science, also expressed doubts, telling us that allowing for greater transparency of IPD while protecting patient privacy was "not at all straightforward".[285] Dr Janet Wisely, Chief Executive of the HRA, stressed the importance of restricting access, explaining that a recent survey indicated that while the public was "very comfortable" with researchers having access to anonymised data, there was "caution" about allowing wider access, for example, by researchers working outside the NHS.[286] Nevertheless, according to Lord Howe, Parliamentary Under-Secretary of State for Quality, Department of Health, there are "ways in which we and the pharmaceutical industry see a way through this"; namely, through the use of accredited safe havens—secure environments within which datasets can be combined and analysed in a way that protects patient privacy.[287]

88. We are not in favour of placing anonymised individual patient-level data (IPD) in the public domain in an unrestricted manner, as we consider that the risk to patient confidentiality is too great and, for many past and current trials, this level of disclosure would go beyond the confines of previously obtained patient consent. Nevertheless, we recognise the scientific value of IPD and consider these data to be currently underutilised. We agree with the Caldicott 2 Review that providing specific individuals with controlled access to personal confidential data such as IPD through carefully managed and secure "safe havens", together with contractual agreements about how that data can be used, is the best way forward. We also consider that access should be facilitated by an independent "gatekeeper", responsible for evaluating research proposals and ensuring that data is handled responsibly and in a way that makes a useful contribution to scientific knowledge.

89. The UK could take the lead in shaping how a global system for sharing IPD for non-commercial trials might operate and a national system covering all non-commercial UK trials would be capable of delivering potentially significant benefits. We consider that the Health Research Authority (HRA) could act as developer, administrator and gatekeeper for a central repository of IPD for non-commercial UK trials. In order to achieve this, template consent forms provided by the HRA should allow for and emphasise to trial participants the benefits of data sharing. Research Ethics Committees should also take into account any transparency restrictions imposed by patient consent forms when evaluating research proposals for clinical trials.

Past initiatives to increase clinical trial transparency

90. Over the last decade, several initiatives have attempted to bring about a greater level of transparency for trials conducted in the UK, Europe and the rest of the world. A brief overview of these initiatives is provided below and is summarised in Figure 2.Figure 2: Past and current initiatives to increase trial transparency[288]


91. In May 2004, the European Medicines Agency (EMA) established the EudraCT clinical trials database, a restricted-access record of all clinical trials of investigational medicinal products (CTIMPs) conducted in the EU.[289] Since March 2011, basic details of the trials contained within EudraCT (excluding phase I trials) have been made publicly available through the EU Clinical Trials Register (EU CTR), and from late 2013 it is planned that the EU CTR will also provide public access to summary-level trial results (although a previous pledge to include results on the register by 2012 was not met).[290] Since 2000, the registry has fulfilled a similar role for US-based trials and is the currently the largest trials register globally.[291] Although largely US-focused, also contains some UK-based trials and, since 2007, has included summary-level results.[292]

92. The EU CTR was described by the academic publisher BioMed Central as a "step towards increased transparency" and many other witnesses also referred positively to the register in their evidence.[293] However, Dr Goldacre described the register as a "failed initiative" which was "incomplete by design" because it contained only "a small subset of all the trials that have been conducted" on a particular medicine.[294] Dr Goldacre explained that:

    The European Clinical Trials Register is a list of trials conducted within Europe over the past few years. It is not a list of all the trials that have been conducted on all the medicines currently available in Europe. It should be, or it should at least strive to be., similarly, is mostly trials conducted in the US, mostly from the past ten years, and with compulsory registration only since 2007.[295]

The Minister stated that the Government had "supported the work of the EMA" in developing EudraCT and described the EU CTR as "a public registry of all trials of medicines in the EU".[296]

93. We received mixed evidence regarding the level of compliance with regulatory registers, including both the EU CTR and its US equivalent, According to Dr Goldacre, a recent US law requiring trial results to be included on "is widely cited as evidence that the problem of missing trials has been fixed. However there was no routine public audit of implementation, and when one was finally conducted [by Prayle et al in 2012] [...] it found that this law has been ignored by four trials out of five".[297] According to the ABPI, a representative of the US Food and Drug Administration has since "challenged the results of the above mentioned study, finding several flaws in the analysis":

    The US FDA's preliminary review of Prayle's results found that instead of 77.9% of trial summary results being overdue, 34.6% trial results were overdue by January 2011. Updating this analysis to May 31 2012, 21.1% of trial results were overdue, a compliance rate of 78.9%.[298]

The ABPI has since conducted its own research which suggested that for US trials of products approved by the European Medicines Agency between 2009 and 2011, 76% had published summary results within 12 months and 89% had published summary results as of January 2013—a far remove from the 22% compliance rate found by Prayle et al.[299] (We note that the ABPI's figures have not been subject to peer review and are based on a smaller and more recent sample of data than the Prayle et al study.)

94. We support the development of the EU Clinical Trials Register (EU CTR) and hope it will also include summary-level results, as promised, by the end of 2013. However, we do not consider the register to represent a complete solution to the problem of non-registration of clinical trials, as it does not include all the trials that have been conducted on all medicines currently available in Europe. The Government should encourage the EMA to further increase the scope of the EU CTR, for example by including phase I trials and trials conducted outside of the EU. We also recommend that the Government monitor the EMA's fulfilment of its pledge to include trial results on the register and obtain an explanation if the EMA fails to do so by the end of 2013.


95. The UK Clinical Research Collaboration estimated that of approximately £8 billion spent each year in the UK on health-related research and development, £3.5 billion is spent by the public and not-for-profit sectors.[300] Two large public funders of UK trials are the MRC, which funds first-in-man and early phase studies[301] and the National Institute for Health Research (NIHR), which, since its formation in 2006, has had responsibility for funding later phase clinical trials.[302] The Government also provides indirect support to many trials funded by the charitable sector through its Charity Research Support Fund (CRSF).[303]

96. During our inquiry we discovered that, while the transparency requirements of the MRC and the NIHR were broadly similar, they varied in their detail. For example, while both required that the trials that they funded were registered and published, only the MRC set out a timescale for publication and only the NIHR stipulated that this must be in a "suitable peer-reviewed journal".[304] Compliance with these requirements, however, is mixed and is substantially below 100%. A 2013 audit of a sample of MRC-funded trials found that 11% had not yet been published and at least 14% had not been registered.[305] We were told that the rate of publication from NIHR-funded research was also variable, although the NIHR's Health Technology Assessment programme, which requires trial registration prior to monies being paid and which publishes research in its own dedicated journal, was unique in achieving "near total and complete publication for its research findings" (estimated to be around 98%).[306]

97. Sharmila Nebhrajani, Chief Executive of the Association of Medical Research Charities (AMRC), told us that 80% of AMRC member charities set out transparency requirements in the terms and conditions of their research grants.[307] Compliance, however, is mixed and not consistently monitored. Nicola Perrin, Head of Policy at the Wellcome Trust, stated that the organisation required all of its trials "to be registered and we expect publication as well", but admitted that "it is not an area that we have actively policed until now" and was unable to provide a current figure for compliance.[308] In contrast, Professor Peter Johnson, Chief Clinician at CR-UK, was confident that his charity achieved a high level of compliance, explaining that:

    It is a condition of funding by Cancer Research UK that any trial is registered. The way we police that is to check at the first annual renewal of the grant that the trial is indeed registered, so we think we have 100% take-up rate for registration and very high rates of publication.[309]

98. When questioned, David Willetts, the Minister for Universities and Science, told us that the Government "would usually expect that publicly-funded research should be made publicly available" and Lord Howe referred to the fact that the NIHR and MRC already required all clinical trials to be published, adding that the Government "would expect compliance [with this requirement] to be 100%".[310] Acknowledging that this was not currently the case, the Government told us that "applicant-declared intentions to register and publish trial results" would be more closely monitored in the future through a software programme called Researchfish.[311] When asked whether current registration and publication policies should also be imposed retrospectively, the Minister pointed out that the Government was encouraging industry to publish the results of past trials, but made no comment on the retrospective disclosure of publicly-funded research.[312]

99. As a major direct and indirect funder of clinical trials, the Government can influence behaviour across both the public and charitable sectors. This influence has not been wielded effectively to increase transparency, meaning that many publicly-funded trials remain unregistered and unpublished. We recommend that registration in a WHO-listed registry and publication of summary-level results in a peer-reviewed journal be made contractual requirements for all publicly-funded trials, including research supported by the Charity Research Support Fund. The wording of these requirements should be standardised across all contracts to ensure consistency. We also recommend that public funders of research rapidly put in place mechanisms to monitor compliance with transparency policies and ask the Government to detail in its response to this Report how and when this will be done.

100. Since the Government has encouraged industry to disclose retrospectively the results of past trials, we think that it should be prepared to do the same for the major trials that it has funded. We therefore recommend a retrospective audit of all public phase III trial grants awarded since 2000, followed by action to ensure that any failures to register or publish the summary-level results of these trials are rectified within 12 months. Any failures to correct these mistakes should be taken into account when considering future grant applications from principal investigators of previously unregistered or unpublished trials. In future, for grants awarded to fund phase III clinical trials we suggest that the MRC and the NIHR allocate a small proportion of funding to cover the time and resource requirements of preparing a manuscript for publication, and withhold this funding until the results of the trial are ready to be published.


101. In 2004, the International Committee of Medical Journal Editors (ICMJE) issued a statement pledging that, in future, "ICMJE member journals will require, as a condition of consideration for publication in their journals, registration in a public trials registry" before recruitment of the first patient.[313] As a result, several leading medical journals, including the BMJ, The Lancet and the New England Journal of Medicine, agreed to require registration as a pre-requisite of publication for all trials initiated after July 2005, and according to PLOS, a not-for-profit academic publisher, since then "many [...] journals, including all the PLOS journals, have adopted this policy".[314] Dr Elizabeth Wager, a freelance writer, editor and publications consultant, claimed that this had brought about "a sharp increase" in trial registration.[315] However, according to Dr Goldacre, research conducted in 2009 showed that "half of all trials published in major medical journals [...] had not been properly registered, and a quarter had not been registered at all", despite the ICJME pledge.[316] PLOS agreed that trial registration was far from universal, stating that it too continued to receive "submissions of unregistered trials" for publication in its journals, which it rejected as a result.[317] We suggest that the academic publishing industry put in place robust measures to ensure that unregistered trials are not just rejected, but that the trial sponsor(s) and funder(s) are notified that the trial has not been properly registered.

Current initiatives to increase clinical trial transparency

102. Since we began taking evidence in early 2013, several developments have occurred at the European and national level which aim to increase the transparency of trials conducted across Europe and the UK.


103. The new EU Clinical Trials Regulation contains several clauses related to trial transparency. According to the current draft, adopted by the European Parliament's Environment, Public Health and Food Safety (ENVI) Committee in May 2013, all trials within the Regulation's scope will need to be registered on a publicly accessible European database prior to initiation and sponsors will also be required to submit to this database summary results "together with a layperson's summary, and, where applicable, the clinical study report" within a year of the trial's completion or termination.[318] The most recent amendments to the draft Regulation were adopted towards the end of our inquiry and so we have limited evidence on their reception by stakeholders. However, when giving evidence a few days after the ENVI Committee's vote, the Minister stated that the Government was "supportive" of these amendments and felt that the ENVI Committee had reached "a sensible and proportionate decision".[319] When asked whether he would have liked to have seen any other changes made to the proposed Regulation, the Minister answered "no".[320] This legislation is scheduled to be debated by the European Parliament in plenary in March 2014 and, if passed, will likely come into effect in 2016.

104. In mandating trial registration, publication of summary-level results and publication of CSRs for commercial trials, we consider that the European Parliament's ENVI Committee appears to have reached a reasonable decision regarding the transparency requirements of the proposed EU Clinical Trials Regulation.


105. In June 2013, the EMA issued for consultation a proposed new policy on access to clinical trial data, in advance of a target implementation date of January 2014.[321] This proposed policy would split the trial data that it receives, including clinical study reports (CSRs) and individual patient-level data (IPD), into three distinct categories:

  • Category one: trial data containing information deemed commercially confidential;
  • Category two: trial data or documents where the protection of personal data is not a concern, either because the document does not contain personal data, or because personal data have been adequately de-identified, and
  • Category three: individual patient-level data for which the protection of patient confidentiality is a concern.[322]

Under the terms of the EMA's revised policy, category one data would remain largely confidential, category two data would be downloadable from the EMA's website and category three data would be made available on request under a controlled-access model. According to the proposed mechanism for category three data, patient privacy would be protected through de-identification and a legally binding data-sharing agreement which would prohibit those accessing the data from using it for unauthorised purposes or sharing it with unauthorised persons, amongst other things.[323]

106. The EMA's draft policy was issued after we had concluded taking evidence. However, we did get a sense from the Minister of the extent to which the Government had been involved in its development. The Government told us that, while Sir Kent Woods, MHRA Chief Executive, had attended the EMA workshop preceding the consultation in his capacity as Chair of its Management Board, "officials from the Department and the MHRA were not present" at subsequent discussions.[324] Government authorities and regulators of several other countries, including the US Food and Drug Administration, the Danish Health and Medicines Authority, the Norwegian Medicines Agency and the German Federal Institute for Drugs and Medical Devices, were represented during these discussions.[325] The Government should clarify why Department of Health or MHRA officials were not present at recent discussions relating to the EMA's revised transparency policy. We hope that the Government will be more fully engaged in the next stages of the development of this policy.


107. Under both the EU Clinical Trials Directive and UK governance arrangements, in order to obtain clinical trial authorisation, all UK trials must first be evaluated and approved by an accredited Research Ethics Committee (REC), currently operated by the National Research Ethics Service, part of the Health Research Authority (HRA). According to the HRA, as part of the research application process "researchers are asked to provide information about the registration of their study [...] and their plans for dissemination of results" and "these aspects are reviewed by RECs".[326] However, in a 2013 HRA survey less than 50% of RECs confirmed that they actively reviewed the intentions of researchers to register and publish their results when assessing a research proposal and a 2013 audit revealed that of a sample of 115 studies, only "33 had done what they said they would do, in publishing, and two phase 1 studies had done likewise, in not publishing".[327]

108. In May 2013, the Health Research Authority (HRA) issued a paper setting out new plans for promoting clinical trial transparency. This included proposals to:

  • make trial registration within an agreed timeframe a condition of Research Ethics Committee (REC) approval from September 2013;
  • develop mechanisms to review actively plans for publication and include them specifically within the condition of the REC approval, and
  • develop simple mechanisms to monitor compliance with REC-approved publication plans.[328]

Dr Wisely, Chief Executive of the HRA, explained that the HRA already had "simple mechanisms to check at the end of the study whether people have registered and published as they should", but admitted that "a better framework" was needed.[329] Nevertheless, under its new policy Dr Wisely stated that for some research the HRA would continue to "rely on the sponsor" to ensure compliance.[330] For instance:

    when the NIHR funds research [...] it ensures that studies are registered and published, so we don't need to double-check. The MRC has got very good rates for publication registering, so it may be that for some we do a random audit within an overall assurance at a sponsor level and for others we do the audit on an application level.[331]

In July 2013, the HRA confirmed its plan of action for improving transparency in health research, but details of this plan do not appear to have been made publicly available.[332]

109. In March 2013, the Joint Committee responsible for scrutinising the Draft Care and Support Bill, through which the HRA will likely be established in legislation as a non-departmental public body in 2013/14, published its report.[333] The Committee recommended that the draft Bill be amended "so that promoting transparency in research and ensuring full publication of the results of research, consistently with preservation of patient confidentiality, becomes a statutory objective of the HRA".[334] The Committee also recommended that the HRA place on RECs "an obligation to include provisions on the publication of research when granting approval for the conduct of research, and an obligation to ensure that such provisions are complied with".[335] In its May 2013 response to the Joint Committee's report, the Government reiterated that it fully supported the principle of transparency in research and would want to take account of the findings of our Report on clinical trials before "determining the HRA's future role in relation to transparency of research".[336] We agree with the Joint Committee that the Care and Support Bill should make the promotion of research transparency a statutory objective of the HRA and we recommend that the Government includes the necessary provision.

110. Research Ethics Committees should have a role in considering and monitoring compliance with transparency policies. As such, we welcome the HRA's new transparency policy and support, in principle, the proposals made in its May 2013 paper. We recommend that the HRA initially retains full responsibility for policing its own policies and ensures that all trials have been registered and published according to an agreed timeline, rather than performing checks on a sample basis. In addition, there must be penalties for non-compliance. We recommend that the HRA provides us with a progress update on implementation of its new transparency policy by the end of 2013.


111. In recent years, select members of the pharmaceutical industry, led by GSK, have taken steps to increase the transparency of the clinical trials that they sponsor.[337] In 2004, GSK became the first company to launch its own dedicated trials register and was quickly followed by other companies including Roche, AstraZeneca and Novartis.[338] In February 2013, GSK stated that it would supplement this register by posting clinical study reports (CSRs) for all future trials and for past trials of approved medicines, and in May 2013 it became the first major pharmaceutical company to put in place a dedicated system aimed at providing researchers with access to the anonymised individual patient-level data (IPD) generated by its trials.[339] According to GSK, requests for access to this data are considered by "an independent panel of experts" conducting "a high-level review of proposals to help ensure that data is used in a scientific and responsible manner".[340] Once a request has been approved, access is provided via a "secure IT environment" akin to the type of safe haven recommended by the Caldicott 2 Review, although this prevents researchers from combining GSK's data with data from other sources, thereby effectively preventing the data from being used for the purpose of meta-analysis.[341] In February 2012, Roche announced that it would implement a similar system to complement its existing clinical trials registry and results database, although it has not announced any plans to provide systematic access to CSRs.[342]

112. In July 2013, the trade bodies the European Federation of Pharmaceutical Industries and Associations (EFPIA) and the Pharmaceutical Research and Manufacturers of America (PhRMA) published their joint Principles for responsible clinical trial data sharing.[343] According to these principles, pharmaceutical companies will make the synopsis section[344] of clinical study reports of many trials publicly available, and will "commit to sharing upon request from qualified scientific and medical researchers" individual patient-level data (IPD), provided that such requests are approved through a "scientific review board" established by the company.[345] Companies will not be required to provide access to IPD if there is "a reasonable likelihood that individual patients could be re-identified", or where this goes beyond the limits of signed patient consent forms.[346] Dr Goldacre described these commitments as "weak and filled with loopholes", but Trish Groves, Deputy Editor of the BMJ, considered that these principles demonstrated that transparency campaigners had "won a battle, if not the war" over greater trial transparency.[347] Implementation of these commitments by EFPIA/PhRMA members will begin on 1 January 2014.

113. We recognise the efforts of some members of the pharmaceutical industry, particularly GSK, to increase clinical trial transparency and hope that other companies will act in the same spirit in implementing industry-wide principles for responsible clinical trial data sharing. We suggest that all companies endorsing such principles agree and report on a common set of clinical trial transparency metrics each year in their annual reports.


114. The AllTrials campaign is an initiative co-founded by Sense about Science, Dr Ben Goldacre, the BMJ, the James Lind Initiative and Oxford University's Centre for Evidence-based Medicine.[348] It was launched in January 2013 and called for "all clinical trials to be registered and results to be reported, from both industry and academia".[349] According to Dr Goldacre, the campaign has "now got the support of 50,000 individuals, more than 100 patient groups and most of the medical and academic professional bodies in the UK".[350]

115. The campaign's website states that AllTrials is calling for the publication of results—"that is, full clinical study reports"from all clinical trials of treatments currently in use.[351] Similarly, Sense about Science recommended to us in its written evidence that "for all trials (phase 2 and above) conducted since 1990 [...] full clinical study reports, or equivalent, should be made publicly available".[352] Applying the terminology used in this Report,[353] Sense about Science and the AllTrials campaign therefore appeared to be calling for the first three levels of trial transparency: trial registration (level 1), publication of summary-level results (level 2) and publication of clinical study reports (CSRs), or their equivalent (level 3). In oral evidence, Tracey Brown, Managing Director of Sense about Science, stated that "the aim of the AllTrials campaign is to ensure that levels 1 and 2 are published" but admitted that the requirements for level 3 still needed to be "ironed out and worked on".[354] Ms Brown later confirmed in supplementary evidence that the AllTrials campaign was only specifically "calling for levels 1 and 2".[355] In August 2013, however, AllTrials published "a detailed plan" of the campaign's objectives in which it stated that the campaign was concerned with the "first three" levels of trial transparency.[356] This document called for all those producing a CSR (or equivalent) for regulatory reasons or "any other purpose" to make the report publicly available.[357] The plan did not set out what information the campaign expected to be included in a non-commercial full trial report or in what circumstances such a report might be prepared.

116. We are supportive of the broad aims of the AllTrials campaign and agree that all clinical trials should be registered and their results reported. We suggest that the AllTrials campaign clearly set out what it considers a full trial report to contain, particularly when prepared for non-commercial purposes, so that its supporters can work together to achieve a specific set of common goals.

Value-based pricing and the renegotiation of the PPRS

117. For most branded medicines, the price that the NHS pays is agreed through a voluntary agreement with the pharmaceutical industry known as the pharmaceutical price regulation scheme (PPRS).[358] The current PPRS, agreed in January 2009, is due to expire at the end of 2013 and negotiations for the 2014 successor scheme are currently underway.[359] Alongside the PPRS, from January 2014 the Government will operate a parallel scheme for establishing the price of newly-licensed branded medicines. Value-based pricing (VBP), according to the Government, will "ensure [that] NHS funds are used to gain the greatest possible value for patients" by more closely aligning the price paid for a drug with the value that it delivers to the NHS and to society.[360] According to the Government, VBP will help to "recognise and reward innovation" and will give industry "clear signals about priority areas, so that research efforts are directed to maximum effect".[361] In light of this argument, we wanted to understand how the Government might be able to use its influence as a customer to encourage other forms of good behaviour, such as increased transparency. When we questioned the Minister about the Government's ability to influence industry, he acknowledged that the NHS was "an important customer for drug companies", and added that "if you speak to the pharmaceutical companies, you may hear them say that the pricing arrangements do have an influence on their decision-making".[362]

118. Value-based pricing (VBP) is predicated on the idea that the Government is able to influence industry's behaviour through its spending power. We therefore consider VBP—and to a lesser extent the PPRS—to be tools that could also be used to encourage and reward industry for making its clinical trial data more transparent. The Government should consider ways in which clinical trial transparency could be incentivised in the future through VBP and the current renegotiation of the Pharmaceutical Price Regulation Scheme (PPRS).

Incorporating emerging evidence into clinical practice

119. Throughout this inquiry, we heard that a key motivation for making clinical trial data more transparent was to improve the evidence-base for treatments currently used by the NHS.[363] If this is to happen, the emerging evidence generated by increased transparency must be taken into consideration in clinical decision-making. We have considered one mechanism for achieving this—the National Institute for Health and Care Excellence (NICE).

120. NICE is an "independent organisation responsible for providing national guidance on promoting good health and preventing and treating ill health".[364] It produces several forms of advice designed to help health professionals make decisions that support "effective, good value healthcare" on the basis of the best available evidence.[365] While it is not currently mandatory for health professionals to follow all types of NICE guidance,[366] Bill Davidson, Acting Deputy Director and Head of Research Standards and Support at the Department of Health, told us that NICE guidance was a "key mechanism" through which emerging evidence reached the "front line".[367] Professor Sikora, Cancer Partners UK and the University of Buckingham Medical School, agreed that doctors "could not deviate" from NICE guidance "because the pharmacy will reject if you prescribe a drug" not recommended by NICE.[368]

121. Fortunately, given its apparent influence, Professor Sikora considered NICE's advice to be high quality and "very well thought out", although he considered guidance to be "too slow" in some cases.[369] The time taken to develop NICE's advice is varied, typically ranging from 9-24 months and "to keep pace with the changes" in medical knowledge NICE stated that its guidance was "regularly reviewed [...] to take into account any new evidence that may influence our recommendations".[370] When asked whether he was satisfied with the timeline for development of NICE guidance, the Minister replied that "if it were the case that it took two years for NICE to do everything, I would not be satisfied".[371] However, he added, "I do not believe that is so", and "over the last few years NICE has significantly accelerated the rate at which it is able to produce results".[372] The Minister told us that "NICE routinely reviews clinical guidelines every three or four years to consider whether they should be updated and can take into account any new evidence" and assured us that "it also has processes in place to bring forward updates if significant new evidence emerges before the scheduled review point".[373]

122. Increased transparency is unlikely to lead to improved medical outcomes unless mechanisms are in place to ensure that emerging evidence is quickly and effectively incorporated into clinical practice. Given the high degree of reliance placed on NICE's guidance by health professionals, we consider it essential that this advice remains fully up to date and that processes are in place to ensure that emerging evidence is rapidly incorporated. The Government should ensure that, as improved transparency leads to ever greater volumes of trial data becoming available, NICE continues to receive the resources it needs to assimilate emerging evidence into its guidance in a timely manner.

178   This inquiry has not focused on the level or type of data used by regulators such as the European Medicines Agency (EMA) or the UK Medicines and Healthcare products Regulatory Agency (MHRA) in making decisions about marketing authorisation. Rather, we have focused on the extent to which information relating to and generated by clinical trials is made available to the scientific community and the public. Back

179   The AllTrials campaign is discussed further in paras 114-116 Back

180   "Home", AllTrials,, accessed September 2013 Back

181   Ev 110, para 3, Q75 Back

182   Ev 79, summary; see also Ev 110; Q87 [Dr Goldacre] Back

183   Ev 81, para 22 Back

184   Ev 67, para 2.2; Q 116 Back

185   Ev 67, para 2 Back

186   Ev w13, para 3, see also Ev 81, para 22; Ev w110, para 23; Ev124, para 4.1; Ev 59, para 2.1; Ev 56, para 30 Back

187   Ev 105 Back

188   Ev w11, para 19 Back

189   Q 88 Back

190   Ev 62, appendix 2 Back

191   Ev 68, appendix 1 Back

192   Ev 88, para 5.3 Back

193   Ibid. Back

194   Ev 98, para A.4; Ev w65, paras 38-39; Ev 109, para 18; Ev w92-93, paras 4.7-4.9 Back

195   Ev w65, paras 36-37 Back

196   Ev w44, para 4.4; Ev 91, para 3.9.1; Ev 88, para 5.1; Q 76 [Mr Burns]  Back

197   Ev w44, para 4.4 Back

198   Q 24 Back

199   Ev 117, appendix para 57; Ev 60, para 3.6; Ev67, para 4 Back

200   Ev 75, para 1.iii Back

201   Q 140 Back

202   See paras 76-77 and 81-84 Back

203   Ev 97, para 22; Ev w120, para 6; Ev w9, para 4; Ev 60, para 3.1-3.2 Back

204   Q 86 Back

205   Ev 84, para 42 Back

206   Ibid. Back

207   Q 57 Back

208   Royal Society, Science as an open enterprise, June 2012, p 7 Back

209   Ev 79, summary; Q 117 Back

210   Ev 82, para 28 Back

211   "About registries: primary registries in the WHO registry network", World Health Organisation International Clinical Trials Registry Platform,, accessed September 2013 Back

212   "About registries: WHO Registry Criteria (Version 2.1, April 2009)", World Health Organisation International Clinical Trials Registry Platform,, accessed September 2013 Back

213   See paras 91-94 Back

214   "About registries: primary registries in the WHO registry network", World Health Organisation International Clinical Trials Registry Platform,, accessed September 2013; Ev 107, para 5  Back

215   Ev 120, para 22; Qq 14-15 [Dr Godlee] Back

216   Q 119 [Ms Brown] Back

217   Ev w29, para 4.1 Back

218   See paras 90-101 Back

219   Ev 114, appendix para 14 Back

220   Q 48 [Dr Elliott] Back

221   Q 224; Q 198  Back

222   See for example "The CONSORT Statement", CONSORT,, accessed September 2013 Back

223   Ev 56, para 30 Back

224   Ev 82, para 30; Ev w41, para 10.1 Back

225   Ev w30, para 4.4 Back

226   Science and Technology Committee, Eighth Report of Session 2010-12, Peer review in scientific publications, HC 856, para 277 Back

227   Ev w80, para 3.1.2 Back

228   Ev w80, para 3.1.1; See also Ev w52, para 12 Back

229   Ev w29, para 3.4 Back

230   Ev w7, para 19 Back

231   Q 30 Back

232   Q 30 Back

233   Ev w77, para 7 Back

234   "The Ingelfinger Rule", New England Journal of Medicine, October 1 1981, vol 305, pp 824-826 Back

235   Ev w30, para 4.7 Back

236   Ev 94 Back

237   A case report form is the document on which much of the information relevant to an individual's participation in a trial is recorded. It may include information such as the patient's age, sex and ethnicity, medical history, results of physical examinations and blood tests and hospital visit dates. Back

238   The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Back

239   "ICH harmonised tripartite guideline: structure and content of clinical study reports (E3)", ICH, November 1995, p 1 Back

240   Ev 108, para 13 Back

241   Ev w8, para 27 Back

242   Ev w9, paras 3.4, 4.2-4.3 Back

243   Q 80 Back

244   Ev w47, para 31 Back

245   "The AllTrials campaign", AllTrials,, accessed September 2013 Back

246   Q 24 Back

247   Q 57 Back

248   Q 59 [Ms Perrin]; European Parliament, Committee on the Environment, Public Health and Food Safety, Draft report on the proposal for a regulation of the European Parliament and of the Council on clinical trials on medicinal products for human use and repealing Directive 2001/20/EC, 31 January 2013, p 51 Back

249   Ev 108, para 13; Q 57 [Dr Elliott] Back

250   Ev 68, appendix 1 Back

251   Ev 112, para 33; P. C. Gøtzsche, "Opening up data at the European Medicines Agency", BMJ, 10 May 2011  Back

252   Ev 75, para 1(iii) Back

253   Q 159 Back

254   Q 159 Back

255   Q 86; Ev 112, para 33 Back

256   Q 75 Back

257   Ev 124, para 4.2 Back

258   Q 215; Q 218 Back

259   Q 218; European Parliament, Committee on the Environment, Public Health and Food Safety, Draft report on the proposal for a regulation of the European Parliament and of the Council on clinical trials on medicinal products for human use and repealing Directive 2001/20/EC, 31 January 2013, p 51 Back

260   European Parliament, Committee on the Environment, Public Health and Food Safety, Report on the proposal for a regulation of the European Parliament and of the Council on clinical trials on medicinal products for human use and repealing Directive 2001/20/EC, 7 June 2013 Back

261   National Audit Office, Session 2013-14, "Access to clinical trial information and the stockpiling of Tamiflu", HC 125, para 7 Back

262   Ev w101, para 25; Ev w44, para 4.6; Ev w81, para3.2.5; Q 24 [Professor Rawlins] Back

263   Ev w1, para 2a Back

264   Ev 77, para 4.6 Back

265   Ev 43, para 4.1.1 Back

266   Ev 98, para A3 Back

267   Q 89 Back

268   Q 76 Back

269   Ev w42, para 17 Back

270   Ev w91, para 3.9.1; Q 139 Back

271   Ev 88, para 5.1 Back

272   Q 140 Back

273   Ev w39, summary; Ev 102, para 4.2a; Q 24 [Professor Rawlins] Back

274   Q 77 Back

275   Q 77 Back

276   Ev w39; Ev41 summary, paras 15.0-15.1 Back

277   Department of Health, The information governance review, March 2013, p 63 Back

278   Department of Health, The information governance review, March 2013, p 63; Q 166 Back

279   Department of Health, The information governance review, March 2013, p 64  Back

280   Q 24 Back

281   Q 104 Back

282   Ev 92, para 25 Back

283   Q 106 Back

284   Q 34; Ev w42, para 18 Back

285   Q 204 Back

286   Q 171 Back

287   Q 198 Back

288   Initiatives: EU Clinical Trials Register (paras 91-94); grant T&Cs = Public and charitable grant requirements (paras 95-100); ICMJE statement =International Committee of Medical Journal Editors (para 101); EU Clinical Trials Regulation (paras 103-104); EMA policy (paras 105-106); HRA policy (paras 107-110); industry initiatives (paras 111-113); AllTrials campaign (paras 114-116) Back

289   Ev 57, para 32-33 Back

290   Ev 57, para 32-33; Ev 115, appendix para 22; Ev112, para 31 Back

291   Ev 95, para 19; Ev 80, para 6 Back

292   Under US legislation, results must be published on ClinicalTrials.Gov for: all trials that have at least one site in the United States; are of a drug, device, or biological agent; and are initiated or ongoing as of September 2007, excluding phase I studies and early feasibility trials of devices. Back

293   For example, Ev w78, para 13; Ev 97, para 26-27; Ev 102, para 5.1  Back

294   Ev 111, para 19; Ev 114-15 ,appendix para 10, paras 18-24  Back

295   Ev 111, para 19 Back

296   Q 215 Back

297   Ev 110, para 6 Back

298   Ev 100, para 3.4 Back

299   Ev 103 Back

300   UK Clinical Research Collaboration, UK health research analysis 2009/10, 2012, p 10 Back

301   First-in-man studies are studies in which a health intervention is tested in a human for the first time. Early phase studies are generally considered to comprise phase I and II trials (see para 9). Back

302   Ev 107, para 3 Back

303   The CRSF came into existence in 2006-07 following changes to the dual-support system for research funding. It was designed to ensure that charities would not have to cover the indirect costs of the research that they funded. For further information see "AMRC guidance on the Charity Research Support Fund", AMRC,, accessed September 2013 Back

304   Ev 107, para 8; Q 49 [Dr Elliott]; Ev w61, para 4.5 Back

305   Q 48 [Dr Elliott]; Q 52 [Dr Elliott] Back

306   Ev w61, paras 4.4-4.7 Back

307   Q 49 (Includes only those members that fund clinical research) Back

308   Q 51  Back

309   Q 49 Back

310   Q 219 [Mr Willetts]; Q 198 [Lord Howe]; Q 225 [Lord Howe] Back

311   Ev 55, para 16; Q 198 [Lord Howe] Back

312   Q 199; Q 225 Back

313   "Uniform Requirements for Manuscripts Submitted to Biomedical Journals", ICJME,, accessed September 2013; "Frequently Asked Questions: Questions about Clinical Trials Registration", ICJME,, accessed September 2013 Back

314   Ev w52, para 13 Back

315   Ev w29, para 4.1 Back

316   Ev 114, appendix, para 14 Back

317   Ev w52, para 13 Back

318   European Parliament, Committee on the Environment, Public Health and Food Safety, Report on the proposal for a regulation of the European Parliament and of the Council on clinical trials on medicinal products for human use, 7 June 2013, p 26 Back

319   Q 200; Q 217 Back

320   Q 218 Back

321   European Medicines Agency, Draft policy 70: publication and access to clinical trial data, EMA/240810/2013, June 2013  Back

322   European Medicines Agency, Draft policy 70: publication and access to clinical trial data, EMA/240810/2013, June 2013, pp 4-5 Back

323   This is a partial list of requirements. For full details see European Medicines Agency, Draft policy 70: publication and access to clinical trial data, EMA/240810/2013, June 2013, pp 5-6 Back

324   Ev 58 Back

325   European Medicines Agency, Clinical trials advisory groups: membership overview, EMA/33488/2013, 20 February 2013 Back

326   Ev 104, para 12 Back

327   Health Research Authority, Transparent Research, May 2013, p 16; Q 151 [Dr Wisely] Back

328   Health Research Authority, Transparent Research, May 2013, pp 4-5 Back

329   Q 153  Back

330   Q 153  Back

331   Q 153 Back

332   "HRA confirms its action plan on transparent research", Health Research Authority press release, 16 July 2013  Back

333   Joint Committee on the Draft Care and Support Bill, Session 2012-13, Draft Care and Support Bill, HC 822 Back

334   Joint Committee on the Draft Care and Support Bill, Session 2012-13, Draft Care and Support Bill, HC 822, para 335 Back

335   Joint Committee on the Draft Care and Support Bill, Session 2012-13, Draft Care and Support Bill, HC 822, para 336 Back

336   Department of Health, The Care Bill explained: including a response to consultation and pre-legislative scrutiny on the Draft Care and Support Bill, Cm 8627, May 2013, para 201 Back

337   See paras 77 and 82 Back

338   Ev 122, introduction, para 3; See also, for example, the trials registers available at, and Back

339   Ev 124, paras 4.2-4.4; Nisen, P. and Rockhold, F., "Access to Patient-Level Data from GlaxoSmithKline Clinical Trials", New England Journal of Medicine, vol 369, 1 August 2013, pp 475-478 Back

340   Ev 124, para 4.4 Back

341   Meta-analysis is a statistical technique in which the results of several independent studies are combined. Back

342   "Roche launches new process for accessing clinical trial data", Roche press release, 26 February 2013 Back

343   "EFPIA and PhRMA Release Joint Principles for Responsible Clinical Trial Data Sharing to Benefit Patients", EFPIA press release, 24 July 2013 Back

344   The synopsis section of a clinical study report (CSR), usually limited to no more than three pages of text, summarises the objectives, methodology, results and conclusions of a trial. Back

345   EFPIA/PhRMA, Principles for responsible clinical trial data sharing, July 2013, p 1 Back

346   EFPIA/PhRMA, Principles for responsible clinical trial data sharing, July 2013, p 4 Back

347   "EFPIA and PhRMA publish principles on clinical trial data sharing", AllTrials,, accessed September 2013 Back

348   Ev 59, para 1.1 Back

349   "AllTrials campaign launch", Sense about Science press release, 9th January 2013; Ev 59, para 1.1 Back

350   Uncorrected transcript of oral evidence taken before the Public Accounts Committee on 17 June 2013, HC 295-i, Q 6 Back

351   "The AllTrials campaign", AllTrials,, accessed September 2013 Back

352   Ev 60, para 3.3 Back

353   Level 1 = trial registration, level 2 = publication of summary-level results, level 3 = publication of clinical study reports and level 4 = sharing of individual patient-level data Back

354   Q 120 Back

355   Ev 74 Back

356   "All trials registered and results reported", AllTrials,, accessed September 2013 Back

357   "All trials registered and results reported", AllTrials,, accessed September 2013 Back

358   The 10% of branded drugs not covered by the PPRS fall within the scope of the statutory pharmaceutical pricing scheme, which was also open for consultation when this Report was published; See "ABPI response to Department of Health's consultation on medicines pricing", ABPI press release, 26 June 2013 Back

359   "Understanding the pharmaceutical price regulation scheme", ABPI,, accessed September 2013 Back

360   Department of Health, A new value-based approach to the pricing of branded medicines: a consultation, December 2010, p 5; p 12 Back

361   Department of Health, A new value-based approach to the pricing of branded medicines: a consultation, December 2010, para 2.16 Back

362   Q 211 Back

363   See for example Ev 116, appendix, paras 47-51; Ev67, para 1 Back

364   Ev w98, para 2 Back

365   "What we do", NICE,, accessed September 2013 Back

366   See "What we do", NICE, for further information on the various types of NICE guidance. Back

367   Qq 172-173; We were not able to identify any data indicating overall take-up of NICE guidance, although information at the level of individual items of guidance is available online at "Search the uptake database", NICE,, accessed September 2013 Back

368   Q 107 Back

369   Q 107 Back

370   "How we work", NICE,, accessed September 2013 Back

371   Q 191 Back

372   Q 191 Back

373   Q 193 Back

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Prepared 17 September 2013