UK Faculty of Public Health Response to the MHRA Public consultation (MLX 376): Proposal to introduce an early access to medicines scheme in the UK
About the UK Faculty of Public Health
The Faculty of Public Health (FPH) is the standard setting body for specialists in public health in the UK. FPH is the professional home for more than 3,000 professionals working in public health. Our members come from a range of professional backgrounds (including clinical, academic and policy) and are employed in a variety of settings, usually working at a strategic or specialist level.
FPH is a joint faculty of the three Royal Colleges of Public Health Physicians of the United Kingdom (London, Edinburgh and Glasgow). In addition, FPH advocates on key public health issues and provides practical information and guidance for public health professionals, aiming to advance the health of the population through three key areas of work: health promotion, health protection and healthcare improvement.
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?
No, such a scheme as described will not be of overall value to patients. The licensing of new medicines was put in place so as to offer an objective assessment of the relative risks and benefits of new medicines before they can come into general use. The current system has worked reasonably well to protect patients and there is no substantive research that allowing medicines into the market place earlier would have achieved major improvements in population health. The opposite is more likely to be true in that allowing pharmaceutical companies to use their medicines on a more limited amount of information will make it easier for them to exploit the positive messages without having to balance these with negative messages.
There is a history of pharmaceutical companies exploiting the current system so as to provide the information in a positive and sometimes unbalanced light. This has been widely commented on and covered in publications. It includes stopping trials early for perceived positive outcomes, which curtails the amount of information likely to be available to help decision making and also gives the research outcomes an undue positivity. Companies failing to publish the detailed outcomes of clinical trials or post licensing finding on side effects are other ways that information is manipulated.
Patients with serious illnesses looking for hope that a cure might happen will be vulnerable to these sorts of one-sided positive messages. There needs to be ongoing protection by the regulatory bodies continuing to need good quality and robust evidence when drugs are ready for marketing.
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)?
Patients with serious illnesses are more likely to be prepared to take risks with treatments that they perceive have the potential to improve their condition. However, even with life-threatening diseases, such as cancer, it is clear that some of the new medicines have serious side effects that have the potential to make the patient’s quality of life worse and could conceivably, if taken in a late stage of the disease, shorten rather than prolong the patient’s life. The Cancer Drugs Fund in England provides lessons in how relatively risky drugs will be used in situations where any benefits are likely to be highly marginal and in reality probably non-existent. Research evidence on many cancer drugs is not usually available for these late disease stages.
Similar comments apply to conditions that are chronic or seriously debilitating. The patient’s ability to benefit from a new medicine needs to be reasonably clearly demonstrated and assessed by a competent and experienced regulatory body as currently happens with the MHRA and the EMA.
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?
One or two medicines per annum seems to be a very small number for what is being proposed and the amount of work going in to considering the idea. It would be of concern if such a scheme were established then the pressure would be on to consider many more medicines at an early stage. The criteria to define a “significant advance in treatment in an area of unmet need” will need tight criteria and to be enforced rigorously. There is a sense of “chicken and egg” here.
If you define something as “unmet need” then there is clearly a need for an effective treatment but the working definition of “need” for an intervention is the ability to benefit from the intervention. If we need robust evidence to demonstrate that a medicine has more benefits than risks then how will we know this until a reasonable amount of good quality evidence is available? Experience of medicines that achieve a truly significant advance shows that they appear possibly once every ten to twenty years, e.g. statins and the 4S study, but not of the order of once or twice a year.
Question 4: Do you have views on the proposed stage of development of a medicine that this scheme will be available?
You have to ask why it takes a year for the regulatory process to deliver marketing authorisation. If the process is unduly bureaucratic then it should be speeded up, or, more likely, that it takes this length of time to discuss issues with the pharmaceutical company and to clarify exactly what the research evidence is saying. If it is the latter case where issues need to be clarified then why should we seek to undermine what is an established system that has proven itself of some worth. There are a number of cases over the years where the system has had to back track on marketing authorisations when the long term evidence has shown the risks to outweigh the benefits. It is difficult to recall examples where it has been the other way round.
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?
If it were to happen it should only take place after phase III trials for the sorts of reasons discussed previously.
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?
Clarity on the phrase, “clinicians other than healthcare professionals” means as clinicians are healthcare professionals would be welcomed.
As regards the information it should be detailed about the pros and cons of the research so far and not seek to hide behind commercial confidentiality.
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?
The information should be detailed about the pros and cons of the research so far and not seek to hide behind commercial confidentiality. It should discuss the degree of confidence behind the experimental findings so far.
Question 8: How much will the impact of monitoring and surveillance arrangements influence your company’s decision to use this scheme?
N/A as comment from NHS based organisation.
Question 9: Please estimate the cost per medicine of setting up a likely surveillance package and appropriate Risk Management Plan (RMP).
N/A as comment from NHS based organisation.
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 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).
N/A as comment from NHS based organisation.
Question 12: Are there other approaches that we could have included here? Please describe.
N/A as comment from NHS based organisation.
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.
This seems a reasonable assumption.
Question 14: Can you quantify likely costs of the limited NICE reviews described here?
N/A as comment from NHS based organisation.
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 reads as the more pragmatic.
Question 16: Can you provide details of any other approaches that could be considered?
In the context of the proposed scheme these seem a reasonable range of options.
Question 17: Do you have any comments on the assumptions made in these options?
The point made in the options that you need good information on clinical effectiveness before you can generate reasonable cost effectiveness is true and may limit this aspect of trying to achieve early access through this sort of scheme. An example is provided by the medicines considered under orphan drug regulations, which achieve market authorisation with a lower quality of evidence than more “everyday” medicines. For these sorts of medicines some of the cost effective estimates have had wide confidence intervals, such as from £500,000 per QALY to £1.5 million per QALY (Eculizumab for PNH).
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?
Something written in plain English that explains the pros and cons and particularly the unquantified risks of the new medicine. When NICE issues a TAG or an IPG on an intervention it is usually worded in relatively technical language. However, NICE usually also issues a plain English version that is much more straightforward and it is clearer even for professionals on exactly what the NICE guidance is saying. It will be important as proposed to comment on what is not yet known. The position of patient groups with an interest in lobbying on behalf of particular patients also needs to be considered as these organisations sometimes lobby for new treatments without discussing the risks and benefits
The liability of individual clinicians who prescribe any unlicensed medicines that have been taken forward through such a proposed early access scheme also needs to be considered.
Question 19: How could such information best be presented?
On official websites and through journals that allow a wider discussion and peer review of any proposals.
Question 20: Do you have any comments on the proposed charges under this scheme?
No.
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)?
The most likely constraint will probably be uncertain NHS uptake particularly as the NHS looks to make more funding judgments based on cost effectiveness and value for money. It is the nature of NHS commissioning to be conservative and not to take unspecified risks with public money or clinical risks on behalf of patients.
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 at: http://www.mhra.gov.uk/Howweregulate/Medicines/Licensingofmedicines/Regulatoryschemesthatsupportdrugdevelopmentlicensingandpatientaccesstoinnovativetherapies/index.htm
If so why?
Unsure as making funding judgments on new medicines is all about the quality of the research evidence in providing clarity on the clinical effectiveness, i.e. the balance of risks and benefits and on the cost effectiveness. It is not clear that the current schemes offer this to any better extent than the proposed early access scheme.
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?
I have no knowledge of this.
Question 24: Do you have any further comments to the content of the scheme that have not been addressed by your previous answers?
Only as an NHS commissioner I would have serious concerns about the practicalities and viability of the proposed scheme mostly as expressed in answer to question 1 and 2.
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.
N/A as comment from NHS based organisation.
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.