The MHRA is undertaking a public consultation on proposals to introduce a scheme in the UK that will provide access to certain new medicines before they are formally licensed. The detail of the scheme, the types of medicines that may be made available and the stage in their development at which we expect that companies will apply are set out in this document.
Application to Northern Ireland, Scotland and Wales:
Responsibility for human medicines legislation is not a devolved matter, but the provision of health services in Scotland, Wales and Northern Ireland is, and it will be for the relevant authorities in these countries to decide on whether to participate in this scheme.
Introduction:
1. The proposed Early Access Scheme was developed following a scientific meeting in September 2007 commissioned as part of a series of events established by the Ministerial Industry Strategy Group (MISG) to consider emerging regulatory issues that may need new approaches. MISG is a committee of pharmaceutical industry CEOs and relevant Government Ministers that considers issues of joint interest in the UK. The focus of the discussion was to consider whether a scheme to deliver early access to medicines might be developed for the UK. The report from the meeting is archived on the MHRA’s website.
The scientific meeting established that stakeholders (patients, healthcare professionals, academics, regulators and industry) considered that early access to new medicines could be of benefit to patients under certain circumstances, and identified the particular issues that would need to be addressed if such a scheme were to be developed.
2. A working group comprising MHRA personnel, representatives from the National Institute for Health and Clinical Excellence (NICE), the NHS, pharmaceutical industry and the Department of Health, including the National Clinical Director for Cancer, developed a framework for an Early Access scheme in the UK.
3. The Working Group was concerned to ensure that this Scheme should be seen in the overall context of other initiatives and schemes (in place or under discussion) at that time which aimed to improve access to new medicines. In particular, these include the various ways in which unlicensed medicines can currently be made available in the UK – although at present these tend to be locally based and ad-hoc in nature.
4. Further development of the Early Access Scheme was postponed last year because of other initiatives ongoing in the NHS, including the development of the Cancer Drugs Fund.
5. In December 2011 the Government published a Strategy for Life Sciences1 with the overall aim of making the UK an attractive place for investment by the life sciences industry. The Strategy commits the MHRA to consult on the Early Access Scheme developed in 2009/10.
The Early Access Scheme in the context of the Life Sciences Strategy:
6. The Strategy for Life Sciences focuses on creating a more progressive regulatory environment that supports and promotes innovation with a view to providing faster access to new medicines for patients. It includes a section that sets out a number of actions with the overall aim of stimulating innovation and growth from start-ups and Small and Medium Sized Enterprises (SMEs) through to large global enterprises. By ensuring that regulation keeps pace with innovation, the Strategy aims to position the UK to realise emerging opportunities in advanced manufacturing and the changing drug development model.
7. The Strategy also comes at a time when there is a growing debate about the changing nature of drug development and the growth of innovations that better tailor medicines to the needs of individual patients. Questions are being asked about whether the current regulatory framework is appropriate, whether it can support the changes needed to reflect scientific advances or whether a more fundamental rethink is required. In particular there are proposals under discussion that fall under the general heading of “Adaptive Licensing”.
8. There are several potential interpretations of this term and it is not currently clear to what extent any of these could operate within the current regulatory framework or whether they will require legislative change. The Scheme developed by the MHRA in 2009/10 on which we are now consulting is not a version of “adaptive licensing” and should be seen as a separate initiative brought forward to respond to a specific Life Sciences Strategy commitment as follows:
“Early in 2012 the MHRA will bring forward for consultation proposals for a new ‘Early Access Scheme’ to increase the speed and efficiency of routes to market approval for innovative breakthrough therapies.”
9. The Strategy sets out the guiding principles for the Scheme as:
“Eligible products will be determined by a scientific opinion that the likely clinical benefits outweigh the risks identified to date where there is high unmet need; NHS funding for product must be cost effective; the UK economy should benefit from the scheme.”
10. The Life Sciences Strategy includes a number of other commitments that MHRA are also taking forward. One, which is now completed, states:
MHRA will take proactive steps to highlight to SMEs the existing regulatory tools to support patient access to innovative breakthrough products, and will report to Andrew Lansley and David Willetts by March 2012 on the range of activities undertaken.
11. Whilst not central to whether and how the Early Access Scheme should be introduced, we are using this consultation to also seek views on the barriers that deter companies from using these existing regulatory tools and to comment on the extent to which the Early Access Scheme represents a real and attractive alternative.
12. Another Life Sciences Strategy commitment that MHRA is taking forward states that:
A group of experts drawn from government, regulators, the NHS, industry, and the academic and third sector communities will meet quarterly to discuss healthcare regulation issues, including the development of new initiatives and innovation.
13. The MHRA is setting up the group that will take forward this commitment and they will have a role in reviewing the outcome of this consultation, as well as considering the issues arising from the broader debate on models of “adaptive licensing” and the continued relevance of the current regulatory framework in the light of technological and other scientific advances. A key point to note is that as the UK operates within a framework of European medicines regulation, any proposal for change to the way medicines are developed or licensed would need EU-wide agreement from all 27 Member States, the European Medicines Agency (EMA), the European Commission and amendment to EU legislation. This is likely to be a lengthy process. Conversely, the proposed UK Early Access Scheme would operate within the current legislative framework and could be in place before the end of 2012.
Comments on Medicines and Healthcare Products Regulatory Agency
MLX 376: Consultation on a Proposal to Introduce an Early Access to Medicines Scheme in the UK
The Royal College of Physicians of Edinburgh is pleased to respond to the MHRA on consultation MLX 376: Proposal to Introduce an Early Access to Medicines Scheme in the UK. Our comments are as follows:
Question 1: Do you consider that a scheme that makes available in the UK certain new medicines before they are granted a marketing authorisation (licence) will be of value to patients?
Yes, in certain very limited instances.
Question 2: Do you have views about the scope of the proposed scheme (for example the type of illnesses and conditions that will be included)?
The scheme would be best suited to drugs for the treatment of illnesses which generally reduce the quality of life over an extended period, or which may be life-threatening in the short term, and particularly when alternative treatments are unavailable or of limited efficacy. The drug should have strong evidence of efficacy, and be deemed acceptably safe at the time it is being considered (ie a positive benefit/risk ratio at the time of consideration for early access).
Question 3: Do you consider that our assessment of the likely number of medicines per annum to which the scheme will apply is accurate? If not, why not? What do you consider might be a more accurate assessment of the number of medicines to which the scheme might apply?
We agree that very few (eg only one or 2) such drugs are likely to be eligible each year. Even that might be an overestimate.
Question 4: Do you have views on the proposed stage of development of a medicine that this scheme will be available?
The gap between phase three trials and licensing seems to be the most appropriate. By that time, a reasonable amount of safety and efficacy data will have been supplemented by data on how to use the drug in special risk groups (eg the elderly and those with liver or renal dysfunction, or on concomitant medication). We would not favour review based on Phase II data alone as safety data would be limited at this stage and it would probably impact on recruitment into Phase III trials.
Question 5: What do you think should happen to patients receiving treatment with a medicine under this scheme if the medicine subsequently fails to be granted a marketing authorisation?
Patients already receiving the drug should be allowed to continue if, in the opinion of the prescriber, it is benefiting the individual, and is also acceptably safe. This could perhaps be achieved using the existing legislation around the supply of unlicensed relevant medicinal products for individual patients (“specials”). Alternatively, patients would be transferred to an alternative treatment, as when a MA is withdrawn, but this would create a difficult situation that would pose major communication and perception problems for the MHRA.
Question 6: What information would patients, clinicians other than healthcare professionals want MHRA to publish on the website when a medicine is given an opinion under this scheme?
Patients should be given access to data on efficacy, based on the pivotal studies, presented in appropriate language, and also information on safety, including confirmed or likely drug interactions. Contraindications and precautions should also be presented in appropriate (non-technical) language.
Healthcare professionals should have access to all the data normally present in a “Summary of Product Characteristics” (SPC).
Question 7: What information about the medicine would be useful for MHRA to publish on the website for use by clinicians, other healthcare professionals and those making decisions about funding?
Since these drugs will incur an “opportunity cost” it would be essential that those making decisions about funding will have access to sufficient data on clinical effectiveness and cost-effectiveness.
Question 8: How much will the impact of monitoring and surveillance arrangements influence your company’s decision to use this scheme?
Question aimed at manufacturer. No informed view.
Question 9: Please estimate the cost per medicine of setting up a likely surveillance package and appropriate Risk Management Plan (RMP).
Question aimed at manufacturer. No informed view.
Question 10: We assume that as most of these medicines will go on to be licensed the need to develop a surveillance package and RMP will not be a critical factor in a decision to use this scheme. Is this correct? If not please explain why not.
Question aimed at manufacturer. No informed view.
Question 11: Please provide an assessment of which of the 5 options (a-e) you consider would be best able to meet the requirement that NHS funding must be cost effective, most likely to most likely to ensure equity of access for patients and most acceptable to stakeholders (especially industry, patients, the NHS, NICE).
We would support option A. The involvement of NICE is very important in ensuring a robust and trusted assessment of cost effectiveness.
Question 12: Are there other approaches that we could have included here? Please describe.
We think this adequately covers the possible options.
Question 13: Please comment on the assumption that whilst the options that include an element of NICE review will incur costs, these will simply advance those costs as the information required will also be required for a later full NICE review.
The costs are incurred earlier but, although the cost of the subsequent review would be less, there would inevitably be some duplication of effort and therefore overall cost would increase.
Question 14: Can you quantify likely costs of the limited NICE reviews described here?
Somewhat less than the present review process. We are not able to put a monetary value on this.
Question 15: Which of the options described is most likely to meet the requirement that this scheme must deliver economic benefit for the UK?
Option b. This option would encourage collection of comprehensive efficacy and safety data to inform assessment of cost-effectiveness. Only if the drug is clinically and cost-effective would it be likely to deliver long-term economic benefit to the UK (eg by saving resources in hospitalisation etc).
Question 16: Can you provide details of any other approaches that could be considered?
No.
Question 17: Do you have any comments on the assumptions made in these options?
We doubt that Option c would increase investment in UK biotechnology companies.
Question 18: What information (in addition to the scientific opinion - see question 6) would patients and clinicians find helpful in deciding about treatment with these medicines?
Information on alternative treatment options (if any) and their benefits in the condition being treated.
Question 19: How could such information best be presented?
There would need to be clear explanation of what an unlicensed drug is, and why the drug in question is being accorded early access, when most drugs will not have been accorded this status.
Question 20: Do you have any comments on the proposed charges under this scheme?
Should the charge for the second year be the same as the first, as the costs are likely to be less than for the first review?
Question 21: What do you think will be the most likely constraints in uptake of this scheme (eg bureaucracy, uncertain NHS uptake, cost of the medicines)?
Uncertain uptake may be an issue, particularly if the NICE guidance in these circumstances does not have the same status as conventional NICE single technology appraisal (STA) advice.
Question 22: Is this scheme likely to be more or less attractive than other schemes that currently offer early access to medicines (these are set out in the accompanying Impact Assessment and in the list recently published by the MHRA) Potentially more attractive.
If so why?
The accompanying bureaucracy could be kept to a minimum, and thus be less burdensome than the other options available in the UK or EU.
Question 23: We understand that schemes in the US that offer early access to medicines are used more extensively than those available in the EU. Is this correct and if so why?
No informed view.
Question 24: Do you have any further comments to the content of the scheme that have not been addressed by your previous answers?
No.
Question 25: Can you identify any costs to your business that might arise as a result of these proposals, particularly administrative and policy or compliance burdens? We would particularly like to hear from you if you can identify an impact upon small businesses.
Question aimed at manufacturer. No informed view,
Question 26: We believe that no small pharmaceutical companies will be attracted to participate in the Early Access Scheme because, as a minimum, these companies would have to have financed Phase II clinical trials, and this suggests that their annual turnover would be higher than the £6.5 million threshold below which companies are classified as “small”. Please comment on our assumption here.
This assumption appears plausible.