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Simon Estcourt assesses how the regulatory landscape for managed access programs is evolving, particularly in the UK.
By Simon Estcourt.
Around the world, many patients with serious illnesses are unable to access the medicines they need. They may have exhausted all available commercial therapies for their disease, they may not have access to a clinical trial, or they may live in a geography where a much needed drug will not be made available through commercial routes. For these patients, access to a medicine outside the clinical trial or commercial setting can represent a new, and in many cases, life-saving treatment option.
“Managed Access” is a term we use to encompass a variety of regulatory approaches used to provide access to medicines outside the clinical trial or commercial setting. These programmes are referred to by a number of names including compassionate use, expanded access, and named patient supply.
These programmes enable patients to gain access to medicines for a variety of reasons:
• The medicine is still in clinical development and has not yet been approved
• The medicine may never be approved, but still offer value for a very small population (for example, some orphan drugs for rare diseases)
• The medicine is approved in one country, but not another
Each European country has their own mechanisms that permit the supply of an unlicensed product to a specific healthcare professional for the treatment of an individual patient and the exact requirements vary from country to country. For example, some countries require some sort of approval to be obtained from their competent authority (e.g. France), whereas others require a retrospective notification (e.g., Ireland).
Demand for access to medicines in advance of licence is predicted to increase significantly over the next decade for a variety of reasons including:
• Patients are increasing empowered with respect to healthcare and have broad access to information on new medicines by patients via social media and global networking.
• A shift in the pharmaceutical industry shift towards more specialised products where the patient and clinical communities are small, and consequently well adapted to pre-approval programmes.
• The global shift from prescriber to payer as the critical success factor for industry.
• Demands on industry to demonstrate cost effectiveness for low volume high cost products at an early stage of development.
In response to growing patient demand, governments are re-assessing and restructuring their access programs. In 2009, the US FDA issued updated regulations regarding expanded access programs.
The new rules provided clarification of rules that had been in place for decades and added new types of access to ensure “broad and equitable access to investigational drugs for treatment.”
Recently, UK Prime Minister David Cameron made a commitment to launch a consultation on an “Early Access Scheme”. The effort is in response to demand for clarification and enhancement of what can be considered practically non-existent regulations.
From our perspective, qualifying entry into an Early Access Scheme should be based on a number of key criteria:
• New medicines that treat, diagnose or prevent life threatening, chronic or seriously debilitating conditions where there is demonstrated unmet need.
• Provisional data that indicates that the medicine offers a potential significant benefit and advantage over existing treatments, and that the risk profile of the medicine is positive.
• That any patient with demonstrated unmet need where their clinician believes that they would benefit from accessing an Early Access Scheme should have the ability to do so.
• The decision whether a patient can access an investigational should be based on expert clinical opinion.
The Medicines and Healthcare products Regulatory Agency (MHRA) already authorises widespread use of unlicensed medicines in the National Health Service (NHS) and an EU legislative framework also exists, although this is not widely used due to variances of Member State healthcare systems.
We suggest the MHRA extend the current arrangements to incorporate the following logical elements:
• The manufacturer makes the decision whether to apply for this type of access. Note that the Association of British Pharmaceutical Industry (ABPI) code of practice stipulates that manufacturers cannot promote medicines prior to licence and may therefore be reluctant to apply. Consideration should therefore be given to allow patient groups and clinicians to request the MHRA approaches manufactures.
• An MHRA working group is established to review criteria for entry based on two key tests of ‘significant unmet patient need’ and ‘indicative data showing significantly improved quality of life.’
• Agreement between the manufacturer and MHRA on data to be collected during the Scheme and patient safety monitoring systems.
• MHRA issues one year approval with the option for an extension if required.
The original discussions around the development of the Early Access Scheme between the MHRA and Ministerial Industry Strategy Group (MISG) of the Department of Health envisaged medicines entering the scheme if they were around a year from full licence and that only one or two would qualify every year. The net effect of limiting the Scheme to one or two medicines which, in common with industry trends, will increasingly treat smaller and smaller patient populations, means that the impact could be negligible unless more medicines qualify for inclusion and at an earlier stage in the lifecycle if the unmet need is significant.
Government policy putting the patient as consumer with an NHS responding to demand, combined with very few medicines entering the Early Access Scheme, could generate political problems for Ministers as patient groups seek improved and equality of access to innovation.
Similarly, the development data on the use of medicines in real life settings via a Scheme would also provide challenges for reimbursement appraisal bodies seeking to understand cost effectiveness and also clinical understanding of efficacy. A potential solution to the issue is for the Scheme to stipulate that real life data can only be available to reimbursement authorities on consent from the manufacturer. Such a move could also help support cultural change within the pharmaceutical industry for the benefit of patients.
Healthcare professionals (pharmacists, clinicians and commissioners) may also be reluctant to provide medicines due to professional liabilities if there was an adverse event related to the Scheme. However, professionals could easily be protected via greater emphasis on patient information and consent, an NHS protocol applicable to all Trusts setting out best practice for the dispensation of the Scheme in Trusts and improved liability insurance for professionals.
Managed Access programs can offer significant benefits to patients and their healthcare providers as they can deliver a new therapeutic option when all alternatives have been exhausted. As demand for access continues to grow, governments around the world will need to keep pace, enhancing their regulations to meet new realities. We look forward to reporting on the new Early Access Scheme under development in the UK.
 European Parliament and Council, Directive 2001/83/EC, Medicinal Products for Human Use, Nov 01
 HM Government, NHS Constitution, Jan 09
Simon Estcourt is Senior Vice President, Strategy and Corporate Development,atIdis (www.idispharma.com) He is a spokesperson and author on behalf of Idis and regularly speaks at International conferences on the subject of access to medicines. Prior to joining Idis, Simon was Sales Director at Servier and Global Business Development Director at Quintiles.