Science and Technology CommitteeWritten evidence submitted by Christopher Lawrence Roy-Toole

About the Respondent

I am a Barrister with an interest in NHS information governance and the regulation of clinical research. I have a visiting scholarship to the Sheffield Law School, now nearing its end, and which has been used to examine the regulatory landscape for medical devices. I have also been involved with the research ethics committee system since 2007. Until I became fed up with the workings of the National Research Ethics Service, and took a leave of absence in January 2013 to regain my composure, I was a volunteer member of the NNT1 Research Ethics Committee in Newcastle upon Tyne [“NNT1 REC”]. It is one of the research ethics committees overseen by the National Research Ethics Service. NNT1 REC handles a wide range of research applications, including those to commence clinical trials of investigational medicinal products at Phases II to IV.

The Select Committee wishes to receive evidence on the functioning of the new Health Research Authority in relation to clinical trials. I can give evidence about that based upon what I have seen as a REC member.

Here are some relevant facts:

In January 2009, I argued that the research ethics committees in the United Kingdom were unfit for purpose and should be replaced with an independent regulatory authority for bio-medical research.

In December 2009, I submitted proposals to the European Commission as part of its public consultation on the functioning of the Clinical Trials Directive. In this, I contended that the roles of the ethics committee and the national competent authority should be merged to create a composite single regulator for clinical drug trial research. This new regulator for clinical drug trials would be better able to disseminate regulatory information to where it was needed and could be “tuned” to apply targeted enforcement action to where it was most required.

I sent a copy of these proposals to the UK Department of Health in January 2010. I did not get a response.

In July 2010, by a happy coincidence, the Secretary of State for Health announced that there would be a review of arms’ length bodies in the health sector with a view to establishing a “single research regulator” for UK bio-medical research.

A collaborator and I then devised further guidance and submitted those proposals to the Academy of Medical Sciences which was, by that time, inviting submissions as to what a single research regulator should look like.

I sent a copy of those proposals to the Department of Health in October 2010. I did not get a response.

So I am unsure about the collective mental process that prompted the Department to announce a “single research regulator”, to set it up as it has been set up, and to style it as the Health Research Authority. But I do know that it does not look anything like the model that I put forward.

Apart from these, I have no competing interests to declare.

Preamble

I shall restrict my responses to only two of the questions posed by the Select Committee:

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

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

Because of the restriction imposed on the length of written submissions, I must adopt an abbreviated approach. The Clerk to the Committee has allowed me a modest extension in length.

This memorandum is therefore intended to direct the Select Committee to relevant matters for further investigation, rather than to provide a comprehensive statement of all matters of fact or law.

If further clarification is required on any matter of law, fact or procedure, then the Select Committee should not hesitate to contact me for further information.

I am willing to give oral evidence to the Select Committee if I am required to do so.

Executive Summary

The “Bonfire of the Quangos” is a grossly wasted opportunity for reform of NHS research regulation and governance. The HRA reflects this fact.

The HRA does not unify the regulatory landscape for research. It fragments it. The UK now has the same problem in NHS clinical research that the Francis Report identified in NHS hospital care: overlapping regulators and a lack of demarcation in function. Patients in research could be put at risk by the continued separation between the MHRA and the REC system.

The HRA has not yet delivered tangible benefits for clinical trials in the UK. Nor will it if the health research Quangos retain their current form.

The solution is to align the MHRA and the REC system closer together so that it can act as one, as if it were a real single regulator. REC members will have to be organised differently and work differently. New opportunities can be grasped if MHRA and REC work together. The cost effectiveness of drug research could be decided at an earlier stage if there were to be real joined-up regulation with NICE.

There are no statutory powers for any UK Quango to compel publication of results from clinical trials or other research. A possible solution is to follow the lead of the Americans and enact legislation to compel publication of clinical trial results. This requires the political will to punish defaulters and the resources to police them. The MHRA is probably the “best of the bunch” to carry out this function.

Regulators and public bodies hold information that is useful to researchers who could use it to examine the safety of existing medicines. There is a case for a new “European Freedom of Information Regulation” to harmonise the rules for access to information held by the EMA and national competent authorities. The way to deal with confidential information is to provide a judicial decision in a speedy and accessible way. There should be a fast-track system established at the Office of the Information Commissioner to enable researchers to apply for information access. The Information Commissioner, not the HRA, should be at the centre of this. Skilled specialist staff and more resources are needed for that.

Evidence

Name of the Beast

Question 1: The role of the HRA in clinical trials

1. The Government hailed the Health Research Authority [“HRA”] as “the single regulator” for health research. But the best way to sum up the HRA is to remember what Voltaire said about the Holy Roman Empire [“HRE”].

2. The HRA was established under statutory instrument and is subject to Directions from the Secretary of State. If the statutory aims of the HRA appear too general, vague, or even conflicting, it is because the Department of Health is still working out what to do with it.

3. It is hard to point to any part of the current functions of the HRA and describe them as “regulatory”. To be a regulator one must have powers of investigation, inspection and prosecution under legal powers. But most of what the HRA is expected to do is of an advisory nature. If the HRA encounters sub-standard research, it is expected to notify other agencies that do have the power to take enforcement action. Outside the REC system, the HRA has no investigative or enforcement powers at all. So one has to ask: what is the HRA there for then and do we really need it?

4. The HRA is not “single” because remains it separate in function and organisation to the Medicines and Healthcare products Regulatory Agency [“MHRA”] and so does the REC. The twin roles of national competent authority and ethics committee were not merged as logic would demand from a “single regulator” for clinical drug trials under the EU Clinical Trials Directive. Compare the working of the Dutch METC and the Hungarian ETT TUKEB.

5. The HRA will also remain separate from the Human Fertilisation and Embryology Authority [“HFEA”] and the Human Tissue Authority [“HTAuth”]. Or at least for now. It very much depends. This is because the Department is still “blowing in the wind” as to what is to be done with these two Quangos. The Department will hold another review of regulation in their sector even though a consultation on their merger has recently been concluded.

Failing to Consult

6. The Government latched onto the idea of a single regulator to add weight to its claim that something would be done to meet the demands of Industry and Academics to cut “red tape”. But the Government failed to consult widely on what needed to be done. It relied too much on the Academy of Medical Sciences to produce the miracle solution. The Academy failed to deliver it. So the Department sidelined the Academy in this. And rightly so. But the Department also shied clear of more radical and “disruptive” proposals that might threaten civil service posts. The Department showed no clear strategy. So it simply put a new label on what it had already. The Department liked NRES because NRES unswervingly did what it was told to do. So NRES became the “HRA core”. Now the HRA is responsible for appointing and overseeing research ethics committees, a job that others used to do, but not much else.

7. To speak bluntly of the HRA: “the Department has put lipstick on a pig”.

Repeating “Mid Staffs”?

8. The danger now is that the HRA will feel impelled to devise new functions for itself, not because they are needed, but because its existence must be justified. Thus, on 19 September 2011, I witnessed the HRA Chief Executive state that NRES must “bid” for new functions or others would bid against them.

9. Consider the wisdom of having multiple and overlapping regulators in the NHS research sector in the light of the Francis Report’s conclusions on “NHS Mid Staffs”.

10. The functional separation between competent authority and ethics committee creates a danger for patients involved in clinical drug trials. It prevents easy collaboration between a research ethic committee and the MHRA for information sharing or joint decision making. The REC needs access to the scientific expertise that the MHRA can provide. This is because experts acknowledge that scientific review cannot be separated from ethical review. The risks, burdens and benefits of research can only be assessed with access to topical advice on the safety profile of the drugs under test.

Holes in the Safety Net

11. The Department of Health obfuscated the issue in its guidance to the REC. The REC has a maximum of 60 days to arrive at a decision and this longstop was set at the insistence of Industry lobbyists. In reality, a REC cannot be expected to make a detailed scientific review in the 10 days or so that they are given to read the papers. So the Departmental guidance does not require them to do so. But it is unreasonable to expect the REC to decline to review the science and to rely solely on “credible assurances” that someone else has examined the science for them. Yet the guidance encourages them to do just that. What is a “credible assurance” and is it more “credible” if it is made by a researcher who comes often before the same committee? So ethics committees very often require their own assessment of the science, despite the state of the guidance. But there is a risk of fish slipping through a ragged net.

12. Patients can be killed just as easily by increased dosages of licensed drugs in Phase II and Phase III of clinical trials as they can by novel molecular entities in Phase I. Yet anecdotal evidence suggests that the research ethics committees that are provided with the scientific opinion of the MHRA at the time of their ethical review can presently be numbered in low single figure percentages. So why are steps not being taken to promote easy access by the REC to MHRA scientific advice in all types of clinical drug trials by changing the way that these bodies are organised or else by merging them ?

13. NRES, MHRA, and the Human Tissue Authority made commitments on paper to share information between each other. Research ethics committees can also have access to specialist scientific advice in high-risk studies as a result of reforms introduced after the so-called “Northwick Park Disaster”. But I do not know of any study that shows how well all this works. And some say that Phase I trials are still the one area of research in which research ethics committees have the least rules to work by. So, despite these changes, where is the evidence that the REC is better equipped now than it was in 2006 when the Brent Medical Ethics Committee approved the TGN1412 protocol?

“Northwick Park” and the Cloud of Unknowing

14. The Department of Health and NRES never published a full report of the facts of “Northwick Park” dealing with the decision of the Brent MEC or the quality of the rules that the Brent MEC was required to follow, especially in the matter of insurance. The Duff Report called for something like that to be made available as a matter of urgency. I did the same in a Departmental journal in 2009. Professor Adam Hedgecoe made his own commentary on “Northwick Park”. He cited institutional habituation and a lack of timely access to independent scientific opinion as causal factors in the sequence of events that lead to the study being approved by the ethics committee. Where is that report?

15. An end must be put to the questionable practice of allowing applicants to cherry-pick a “REC-u-Like”. Some applicants avoid a “hard” REC.

No Benefit Yet

16. The HRA has not yet delivered any additional and conclusive benefits to the regulatory process for clinical drug trials. The HRA claimed that it would deliver a “one-stop” platform for researchers making applications for research approval to both the MHRA and the ethics committee. This was to be done through the optimisation of its existing IRAS online portal. IRAS cannot deliver this joined-up working in its present state and the project has been put on hold. So what will replace IRAS, if anything, and will it also have the ability to deliver joined up working between MHRA and HRA?

“Two Legs Bad, Eight Legs Good”

17. The decision to keep the HTAuth and HFEA separate from the HRA also compounds an existing problem about how to deliver joined-up regulation and oversight for clinical trials involving Advanced Therapy Medicinal Products. How will the HRA now deliver a “one-stop” submissions platform for Advanced Therapy trials that require approval from HFEA or HTAuth?

18. The need for joined-up working between MHRA and ethic committee will become more acute after the introduction of the European Clinical Trials Regulation. This is because there will be a central portal for clinical trial authorisations at European level and national competent authorities and national ethics committees will be expected to make their own arrangements in order to work with it. The most efficient “national team” will win business from the rest. At present, the United Kingdom is not “match fit”.

Misadventures in NHS R&D

19. So why is the HRA currently fixating on ways to ease the burden on the NHS R&D Departments that oversee the governance of research on individual NHS sites? The Select Committee might like to ask what the NIHR HRA Feasibility Study and Pilot hopes to accomplish and whether the money should be better spent on improving common working at the “sharp end” of regulation, in the approvals system between the REC and the MHRA.

20. NHS R&D Departments need more radical solutions than a pilot study to save them from inefficient working. Moving research functions out of NHS Trusts and into state sponsored corporate enterprises with single-point management responsibility might be one way forward. But that idea is outside the scope of the current Inquiry.

Converge or be Damned

21. The REC is made up of volunteers. This puts the entire edifice of HRA/NRES on an increasingly shaky foundation. Committee meetings have risen from one per month to three. There are frequent begging emails asking for volunteers to make up the numbers. Perversely, the volunteer must now expend added effort to fast-track the “small stuff” in research that cannot be classified as a clinical drug trial. NRES calls it called “Proportionate Review”. But it is unpopular with volunteers because it places a disproportionate burden on them. It would have been more sensible to fast-track the “Big Stuff” instead. The workload should be spread across smaller ethics review teams. Lay volunteers should be spared the mounds of scientific paperwork that they cannot decipher unaided and be allowed to focus on the patient’s standpoint in research.

22. The solution now is to collapse the research ethics committees into regional centres to pool manpower resources. In these regional centres, the HRA and MHRA must work together in a synchronised manner to handle clinical trials of drugs and devices. But they must also share their information for a range of regulatory purposes, of which some are necessary now and others in the near future. Consider the cost savings that might result if MHRA and ethics committee could in future work together with NICE to deliver a “hybrid assessment” from the outset. This means that clinical drugs trials would be assessed not just for safety and efficacy, as they are now, but also for cost-saving effectiveness and the impact on patients’ quality of life.

23. This requires RECs to be overhauled by: (1) making the transition to full time operation using a skilled cadre of independent-minded ethical reviewers under proper contracts for services and; (2) providing support functions that really matter to protect the patient, not the civil servants, or for that matter, the vested interest groups in research.

Publication or Penalties

Question 2: How to make clinical trials more transparent and who must do it?

“A statutory duty to publish results”

24. The Select Committee should consider the case for new law comparable to the US Food and Drugs Administration Amendments Act 2007 to mandate the publication of results by all researchers in UK clinical trials. It must enable substantial financial penalties to be levied on defaulters and perhaps other economic penalties besides.

25. Would an EU-wide Regulation for research publication be the best answer to allow for a solution across the entire Northern Hemisphere?

26. Evidence from the United States shows that statutory rules for the publication of clinical trial results are not enough. Voluntary codes of publication linked to “soft” penalties such as funding restriction or editorial bars are too much in their infancy to form a view about their effectiveness. Using penal sanctions to encourage publication and punish non-compliance might work better.

27. What is the experience in the United States in the interplay between US FDAAA 2007 and the US Freedom of Information Act? Where are the “pinch points” for them and for us? UK FOIA allows information to be withheld before publication. The Scots FOI law has a specific research exemption. So would a statutory duty to publish conflict with relevant exemptions under FOI laws? How to resolve it?

‘Toothless Publication Tigers’

28. The REC cannot monitor publication of results from clinical trials because the publication duty usually arises after the research has been completed. The role of the REC ends with the conclusion of the research study. Therefore it is not an effective tool to police publication of research. The HRA Chief Executive was wrong to suggest otherwise in a recent letter to the BMJ.

29. The HRA may soon instruct the REC to take a bad publication history into account in deciding whether to give a favourable opinion to a new research application submitted by the same sponsor. The REC has no legal powers to compel publication of results. So this might expose the REC to complaints that it had acted ultra vires and so to judicial review.

30. The HRA wants to set up a system to monitor whether researchers who apply through IRAS are living up to any commitment to publish results. It has not said how. The MHRA controls the portal to the Clinical Practice Research Datalink. The NIHR controls its own database of portfolio studies. The HRA only controls a database with summaries of research projects that began with approval from a UK REC. The HRA has no special legal power to access other people’s databases. There is no joined-up governance of NHS research databases to show who is publishing what in UK research.

New Job for the MHRA

31. So no Quango in the United Kingdom is best placed to monitor compliance with a legal duty to publish research. Without comprehensive monitoring of compliance under a real single regulator with powers of information access, enforcement in the UK will remain patchy at best.

32. Because the MHRA has inspection and enforcement capabilities, there is no option but to entrust it with the task of investigating and punishing breach of any special laws that require publication of research data from clinical trials of drugs and devices. The FDA now does it in the USA. But it comes down to resources.

Public Versus Private Interests

Public Access and the Public Interest

33. This is the problem in access to research data: there is a tension between the public right to access information that is held by the State and the right to expect that legitimate private interests will be protected whenever the State acts in a regulatory capacity. The tension can only be resolved by deciding what is justified in the public interest. This can only be decided by someone with judicial powers.

34. If decisions about the release of confidential information could be speeded up, then clinical trials might become more transparent.

35. Protecting commercial interests and regulatory activities are the main grounds on which a regulator must treat information as confidential. But an EU Regulation and the UK Freedom of Information Act 2000 both allow confidentiality to be overridden if the public interest justifies disclosure of information about marketed drugs and clinical drug trials. The proposed Clinical Trials Regulation does not alter this. Contrast the position for medical devices, where outdated EU laws prevent disclosure.

Data Access under the Regulation

36. The proposed European Clinical Trials Regulation will establish a central database of information received through an EU portal for applications for clinical trials authorisation and for the submission of safety data about tested drugs. The public will have access to this central database unless confidentiality claims can be “justified”. It is likely that the European Medicines Agency will manage the database.

37. But how will the proposed Clinical Trial Regulation affect:

The citizen who seeks information that is held by the EMA but which is not otherwise featured on the database?

The citizen who reads information from the central database that leads him to request other information that is held only by the national competent authority in his own member state?

The citizen of one member state who requires access to information held by a different competent authority in another member state?

Multiple applicants from multiple countries who want access to the same data originating from the same clinical trial or the same marketed drug and all at the same time?

Who decides whether the citizen can have access to data: the EMA or national competent authority?

Who must the citizen appeal to when access is denied: the Ombudsman or the national tribunal that adjudicates on access to public information?

European Freedom of Information

38. At present, a citizen must complain to the European Ombudsman to compel the European Medicines Agency to give access to its information. The Ombudsman’s powers appear to be persuasive and advisory. The citizen would be better off if he had access to a regulatory body that could compel access to data held by the EMA and the national competent authorities. There would be certainty. The European citizen would benefit even more if he could appeal to a regulatory body in his own country that could grant access to information held on the EU database or by a competent authority in another member state. It would be faster and cheaper.

39. Look at what the European Union is now doing to overhaul national laws on the processing and free movement of Personal Data in the European Union. We can extract from that to develop a better approach to public access to information about medicinal drugs. So:

(a)We need a “European Freedom of Information Regulation” to harmonise national laws providing for public access to government information.

(b)Every member state must have a supervisory body for Freedom of Information just as they must for Data Protection. These must have the power to compel disclosure, as the UK Information Commissioner does.

(c)Each national supervisory board must be sufficiently similar to allow for joint operations and joined-up thinking.

(d)There must be a “consistency mechanism” to enable decisions on data access to be taken by one supervisory board and applied across borders of member states. In that way, clinical data could be accessed no matter where it is deposited across the EU regulatory apparatus. Fragmentation of the clinical data landscape is a major problem and this could help fix it.

(e)Consistent rule making can be assisted by the formation of a European Freedom of Information Advisory Board, similar to that proposed for Data Protection.

40. The national competent authority should decide whether to allow access to information held within the EU database, not the EMA. To avoid “black holes” in data access, the competent authority should be deemed to have total access to all data held by EMA on or off the database.

41. The national competent authority should be answerable to a Freedom of Information supervisory authority in every member state. This would allow the citizen to seek access to data through his own national institutions.

42. There would be no need for a European super-regulator and the Ombudsman might be permitted a lesser role in handling the disputed disclosure of clinical data from research.

Fast Track Information Access for Research

43. In the United Kingdom, the Office of the Information Commissioner should be given funding for a specialist department acting under new enabling powers. Its purpose would be to make enforceable decisions on the disclosure of confidential information held by regulators and other public authorities, including Universities, concerning clinical trials and marketed drugs. The powers would engage in those cases where information access is required for the purposes of secondary research. The new powers would focus on commercially sensitive information and regulatory information.

44. The Information Commissioner’s special department would need the resources to assess the scientific merit of the application for data release. We must not encourage a “free for all” amongst those academics who only wish to make a name for themselves by nit-picking over someone else’s data.

45. It would be a fast-track decision process to handle information access requests in those cases where fast-tracking is thought necessary. Fast-tracking should be reserved for those cases in which the requested data is to be used for secondary research. This can be justified on two grounds: (1) secondary research analysis of existing clinical data can yield public benefits and (2) researchers could be made to operate under special terms of professional confidentiality that could not be placed on a member of the public.

46. The Information Commissioner is the correct candidate for these new powers, not the HRA. The HRA has no powers to order information release under FOI laws.

47. Section 251 National Health Service Act 2006 provides a template for the sort of powers that the Information Commissioner’s team would need. Section 251 allows the release of identifiable and confidential patient information without consent. Data security measures can be required as a condition of access.

48. One must therefore question the wisdom of transferring the section 251 advisory group out of the National Information Governance Board and into the HRA. It should have been aligned with the Information Commissioner to give independent and specialist assessment of information handling in the NHS.

49. The MHRA and the other regulatory agencies will have to engage in joined-up working with the Information Commissioner under new powers if they are serious about giving effect to data transparency in clinical research. They must also share information to allow agreed standards to be drawn up. But some of the Information Commissioner’s staff will need to be re-educated as to what is expected of them. One policy worker indicated to me that ICO would not submit evidence to this Inquiry because it was all to do with drug companies and so had nothing to do with them. Worrying, is it not?

February 2013

Prepared 16th September 2013