Science and Technology CommitteeWritten evidence submitted by GlaxoSmithKline

Introduction

GSK is a global healthcare company that researches and develops a broad range of innovative products. We make medicines, vaccines and consumer healthcare products that are used by millions of people around the world, allowing them to do more, feel better and live longer.

Our focus on responsible, values-based business underpins everything we do including how we conduct and report our research. Business decisions are guided by our GSK values to: commit to transparency; show respect for people; demonstrate the highest integrity in our conduct; and be patient-focused. The activities described in this paper demonstrate our commitment to embed greater openness within the fundamental ways in which we work.

We are committed to being transparent with clinical trial data to help advance scientific understanding and inform medical judgment. Since being the first company to launch an internet-based clinical study register in 2004, we have expanded our approach and provided earlier access to greater information. This evidence submission describes recent commitments to publically disclose Clinical Study Reports (CSRs) and provide researchers with an opportunity to access anonymised patient level data to undertake further research. Our commitments acknowledge the contribution made by the individuals who participate in clinical research. All those involved in the conduct and publication of clinical research have a role to play in ensuring that the data they generate are made available to help bring patient benefit.

1. Do the European Commission’s proposed revisions to the Clinical Trials Directive address the main barriers to conducting clinical trials in the UK and EU?

1.1 The proposals in the Regulation are broadly welcomed and should reduce the time and number of approvals needed to set up clinical trials. New timelines for the submission and review of a single Clinical Trial Application (CTA) for multi-country trials could speed up the initiation of clinical trials, without compromising the safety of research participants. The new process and timelines should be supported, with no additional complexity added as the proposals progress through the legislative process.

1.2 GSK supports in principle the establishment of an EU database containing information on applications for and results of clinical trials. Further clarity is needed on the content of the EU Database and mechanisms to protect personal information and any commercially sensitive information.

1.3 UK-specific assessments, including NHS R&D approval, need to be delivered within the same timelines established in the Regulation. Barriers to conducting trials in Europe should be reduced by the Commission’s proposals. To protect the UK’s competitiveness and capture the benefit to patients of taking part in trials, additional UK approvals need to be made in parallel to the legislated requirements of the Regulation. The progress started by the Health Research Authority, MHRA and National Institute for Health Research in streamlining UK decisions needs to be maintained.

2. What is the role of the Health Research Authority (HRA) in relation to clinical trials and how effective has it been to date?

2.1 The role of the Health Research Authority should remain focused on removing complexity and delays in the UK approval process. We welcome the HRA’s commitment to begin testing plans in Spring 20131 to combine and replace aspects of the current reviews by NHS R&D and Research Ethics Committees (RECs) into a single assessment. The effectiveness of the HRA needs to be measured against its ability to deliver a simplified and streamlined process.

2.2 The HRA was established to correct past practice of layering new, well-intended checks and approvals onto the UK approval pathway.2 Any role for the HRA in monitoring compliance against transparency commitments (eg reviewing past publications) needs to avoid adding delays to UK research approvals. Sponsors and funders of research should review past compliance with disclosure commitments when assessing new research projects.

2.3 The positive start made by the HRA in addressing unnecessary complexity should be allowed to continue; a number of significant challenges remain. Efforts by the Department of Health, NIHR and the HRA to streamline research approvals are to be applauded. Approval timelines across NHS sites remain variable and many improvements remain planned or in pilot form, however early evidence shows a reduction in approval times.3 We want to work with investigators, NIHR and Trust R&D staff to improve the UK performance in embedding high quality commercially funded research as a core function of the NHS. To increase the number of UK patients in trials and the effectiveness of the HRA, a number of outstanding issues need to be addressed:

The efficient and reliable start up of trials, with patient recruitment completed to time and target.

The further streamlining of cost and contract negotiation with NHS Trusts.

The failure to deliver full electronic submissions for NHS RECs and the MHRA—a system that had been presented as being integral to creating a unified process—appears a backwards step.4 Further clarity is needed on how the HRA will work closely with MHRA and NIHR.

3. What evidence is there that pharmaceutical companies withhold clinical trial data and what impact does this have on public health?

3.1 Patient safety is always our priority. We evaluate the benefits and risks of our medicines at all stages of research and after a new product is approved for sale. Pharmaceutical companies are legally required to disclose results from clinical trials to the appropriate regulatory authorities. After approval, companies have a continuing obligation to provide regulators with updated safety information from clinical research and other sources.

3.2 GSK fully supports steps to drive greater transparency of clinical trial data and to help medical research by allowing scientists to study the detailed results of clinical trials and increase understanding of current and new medicines. Ultimately this should improve patient care. We recognise that there are concerns about the extent to which all clinical trials (both industry and academic trials) are published and whether published information accurately reflects the conduct of the study. This evidence submission focuses on our ongoing commitment to promote greater transparency.

Evidence of disclosure and compliance with policies

3.3 Our commitments reflect a desire to promote transparency, facilitate further research and ensure that the data provided by research participants are used to maximum effect in the creation of knowledge and understanding. Detail on our commitments is in our Public Policy on “Public Disclosure of Clinical Research”5 and information on recent initiatives under question 4. In summary our policies are:

Public trial registration: when studies are initiated, protocol summaries are posted on internet registers.6

Disclosure of results:

Result summaries are posted on public registers and studies submitted for publication in journals—irrespective of the outcome of the study.7

We will not wait until approval or termination of the medicine before posting results summaries or submitting manuscripts to journals.8 Publication of results takes place within timelines from the completion of studies.

Public disclosure of Clinical Study Reports (CSRs): In February 2013, we committed to post CSRs, with personal information removed, once the trial has been published and the medicines have been approved or terminated from development (see 4.2).9

Access to anonymised patient level data: we will shortly be launching a system to enable researchers to request access to underlying patient level data to conduct further research (see 4.3).10

3.4 We have embedded processes to monitor our performance against our own targets. In many cases these targets go beyond the industry minimum or practices in other sectors.11 Steps to disclose information and measure compliance have become an integral part of the trial process:

By the end of 2012, our public Clinical Study Register contained 5,000 results summaries and received an average of 11,000 visitors a month.

Since committing in 2009 to seek publication of all human research as manuscripts in the scientific literature we have submitted over 2,100 publications.12 In 2012 we raised internal visibility of these obligations, increased use of internal metrics and provided additional support in publication planning, development and reporting.

We are committed to getting information out to the scientific community in a timely fashion. For manuscripts submitted in 2009–12 we have seen a marked decrease in time from the end of the trial to the submission of a manuscript. Likely drivers for this include use of tracking systems and internal communication of metrics.

Impact on public health and further scientific research

3.5 When patients volunteer for clinical trials it is a legitimate expectation that the results will be used to help others. To accelerate the discovery of new medicines and vaccines, we make collaboration part of our business model. Our Open Innovation strategy is designed to promote change beyond GSK by sharing expertise, resources and intellectual property and know-how with external researchers and the scientific community. Providing access to information, sharing knowledge and reducing duplication is fundamental to the common goal of advancing science.

3.6 Our transparency efforts are not limited to clinical trials. From 2009, we have included all our observational studies and meta-analyses that evaluate our medicines on the GSK Clinical Study Register. In January 2009, in recognition that information from terminated research programmes can inform the scientific community and help reduce exposure of study participants to similar compounds in other clinical trials, we extended our disclosure commitment to all our studies of terminated compounds.

4. How could the occurrence and results of clinical trials be made more open to scrutiny? Who should be responsible?

4.1 Providing access to further detail on the methods and results of trials promotes trust, avoids unnecessarily enrolling patients in trials and enables others to conduct further research. This subsequent research may be in new areas or enable others to identify important findings of relevance to GSK medicines. We look to provide access to information in ways that protect individual privacy and promote the responsible use of data. Since being the first company to launch an internet-based clinical study register, we have looked to meet changing expectations by expanding our approach and providing earlier access to greater information. The sections below describe recent steps to enable greater scrutiny of clinical trial information by providing further information in addition to protocol and result summaries and journal publications.

Public access to Clinical Study Reports (CSRs)

4.2 In February 2013, GSK committed to post CSRs, with personal information removed, on our public register once the trial has been published and the medicines have been approved or terminated from development.13 CSRs are formal study reports that provide detail on the design, methods and results of trials and form the basis of submissions to regulatory authorities. To ensure patient confidentiality is maintained, the core CSR will be posted after removing patient information. While there are practical challenges, we also intend to publish CSRs for clinical outcomes trials for all approved medicines dating back to the formation of GSK. This will require retrieval and examination of each CSR to remove confidential patient information. Given the volume of studies, this work will be completed in a step-wise manner, with priority given to the most commonly prescribed medicines.

Access to anonymised patient level data

4.3 In October 2012, GSK announced that we would create a system to enable researchers to access anonymised patient level data from published trials of our approved or terminated medicines. Researchers will be able to request data from global patient studies conducted since 2007 and over the next two years we will include global patient studies going back to the formation of GSK. We will also include all patient studies we start in and after 2013.

4.4 This initiative will enable researchers to examine data more closely, to conduct further research to help optimise the use of medicines and ultimately improve patient care. Requests for access to data will be reviewed by an independent panel of experts. The panel will undertake a high-level review of proposals to help ensure that data is used in a scientific and responsible manner. To protect individual privacy, anonymised patient level data will be accessed in a secure IT environment. There will be controls in place to restrict the ability of researchers to download the anonymised data. Researchers will sign a data sharing agreement requiring them to publish their research and only use the data for the agreed purpose.

4.5 We recognise that our commitment is a first step. There may be other ways for further research to be conducted using these data and our approach may evolve as we gain experience. We hope this initiative and what we learn will catalyse the development of a broader system where access to anonymised patient level data from all clinical studies conducted by industry and academia are made available for further research.

European Medicine Agency (EMA)

4.6 We welcome the EMA’s efforts towards greater transparency. Their ongoing consultation explores how clinical trial information, including clinical study reports, can be “proactively published” once the decision making process on an EU marketing authorisation is complete.14 The CSRs provided to the EMA include patient level information in the appendices and main report. We encourage the EMA to identify an appropriate solution that protects patient confidentiality, ensures that the subsequent use of information is aligned with the original consent provided by patients and promotes the responsible use of data. We continue to provide input into the EMA consultation. One option may be for the EMA to progress in a step-wise manner, beginning with the publication of the core CSR (including aggregated information, but not the patient-level data in the report and appendices).

Who should be responsible?

4.7 Solutions need to be developed in collaboration with patients, regulators, journals and researchers from all sectors. We hope that our commitments will catalyse the development of further efforts across industry and academia. It is important that steps to greater transparency include all patient trials, including the many studies conducted in academia.

4.8 Information needs to be provided in an accessible and usable manner and we caution against the further proliferation of public registers, which duplicate information and impose variable requirements. Embedding cultural change across organisations and raising visibility of transparency obligations may also reap benefits. We seek to promote transparency when entering research collaborations, including, for example, adding a requirement to the standard NHS model Clinical Trial Agreement that (unless it is an exploratory trial) the Sponsor shall submit the trial for listing in a public registry within 21 days of initiation of patient enrolment.

5. Can lessons about transparency and disclosure of clinical data be learned from other countries?

5.1 The steps we have taken are global commitments that reflect the fact that clinical trials are conducted all over the world, with any one study often involving sites in multiple countries. Introducing country-specific requirements could delay the approval of research and will impact on only a small subset of global trials. We hope the experience gained through our own initiatives will be of value in developing global approaches that promote further research to learn more about how medicines work in different patient populations and to help optimise the use of medicines with the aim of improving patient care.

March 2013

1 http://www.hra.nhs.uk/hra-news-and-announcements/hra-given-go-ahead-for-feasibility-study-hra-assessment-for-approval-of-research-in-the-nhs/

2 The Academy of Medical Sciences (2011). “A new pathway for the regulation and governance of health research” http://www.acmedsci.ac.uk/download.php?file=/images/project/130734957423.pdf

3 Data presented at the NOCRI/ABPI/BIA R&D Conference in November 2012.

4 http://www.hra.nhs.uk/hra-news-and-announcements/future-of-iras/

5 http://www.gsk.com/content/dam/gsk/globals/documents/pdf/GSK-on-disclosure-of-clinical-trial-information.pdf

6 For example: http://www.clinicaltrials.gov/ and https://www.clinicaltrialsregister.eu/ and/or our own register http://www.gsk-clinicalstudyregister.com/

7 This commitment includes all our clinical trials (phase I-IV) as well as our observational studies and meta-analyses that evaluate our medicines. The GSK Clinical Study Register, created in 2004, includes studies since the formation of GSK in 2000 and some earlier studies where results inform medical judgement.

8 Our approach is to post result summaries on the GSK Clinical Study Register with 8–12 months of the completion of studies and to submit a manuscript to a peer reviewed journal within 18–24 months.

9 http://www.gsk.com/media/press-releases/2013/GSK-announces-support-forAll-Trials-campaign-for-clinical-data-transparency.html

10 http://www.gsk.com/media/press-releases/2012/GSK-announces-further-initiatives-to-tackle-global-health-challenges.html

11 For example, our commitment to seek publication of all our clinical research goes beyond the existing industry-wide (IFPMA) obligation to submit all Phase 3 results and others of significant medical importance for publication. Our commitment to post on our register phase I studies, observational studies and meta-analyses that evaluate our medicines goes beyond what is required by regulations in the US and EU.

12 This figure includes primary, secondary and discretionary publications.

13 http://www.gsk.com/media/press-releases/2013/GSK-announces-support-forAll-Trials-campaign-for-clinical-data-transparency.html

14 http://www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/general/general_content_000555.jsp&mid=WC0b01ac0580607bfa

Prepared 16th September 2013