New Medicines Reviews 2013

THE ROLE AND REMIT OF NHS BOARD AREA DRUG AND THERAPEUTIC COMMITTEES AND INDIVIDUAL PATIENT TREATMENT REQUEST ARRANGEMENTS

APRIL 2013

REMIT OF REVIEW OF ADTCs and IPTRs

In November 2012, I agreed to chair a short life working group to refresh the role and remit of the Area Drug and Therapeutic Committees (ADTC); in November 2012 the Cabinet Secretary for Health and Wellbeing announced a more comprehensive New Medicines Review. I agreed to extend my examination of the function and role of ADTC and to examine the extant Individual Patient Treatment Requests (IPTR) arrangements and report to the Chief Pharmaceutical Officer. The published remit is attached at Appendix 1.

In December 2012, the Health and Sports Committee of the Scottish Parliament considered petitions submitted on behalf of patients with very rare diseases who were unable to access medicines in Scotland. These very rare conditions are termed "ultra-orphan^[1]" conditions and are widely accepted as those occurring in less than 1000 people in the UK (equating to less than 100 people in Scotland). Scottish Medicines Consortium (SMC) "not recommended" advice for these conditions may be made either on the basis of a "non-submission" or because the clinical and cost-effectiveness has not been demonstrated. In January 2013, I provided interim advice to the Cabinet Secretary for Health and Wellbeing to consider the availability of a new Orphan Drugs Fund. The Cabinet Secretary announced that this fund would be available from March 2013, and I have considered proposals for how this would operate alongside the existing arrangements.

CONTEXT

The introduction of new medicines to NHS Scotland is important for patients, the NHS and society. In October 2012, Medicines and Healthcare Regulatory Agency (MHRA) confirmed there were over 12,000 market authorisations for all forms and strengths of Prescription Only Medicines (POM) containing 1500 different active substances available in the UK for regular use and the SMC consider about 60-80 of these each year. The Charles River Associates report^[1] demonstrated that Scotland is not significantly different from other EU countries with regard to access to novel^[2] medicines. The proportion of positive recommendations was higher than Canada, the rest of the UK or Sweden. This report found that the SMC demonstrated an increased speed in appraisal for novel medicines when compared to other submissions and was the only country included in the study where this was the case.

The arrangements for the introduction of new medicines into NHS Scotland were detailed in CEL 17 (2010) and expanded further in SGHD/CMO (2012) 1. The SMC makes decisions on which licensed medicines are 'accepted for use', and which are not, in NHS Scotland. SMC decisions are advisory but NHS Boards are expected to take full account of SMC advice and ADTCs are expected to make local decisions about SMC "accepted" medicines quickly.

However, only about one third of SMC advice is related to novel medicines. The majority are new formulations of existing medicines or new chemical entities within a class of existing medicines and may offer no or limited evidence of increased clinical benefit to patients, and often at increased costs. SMC may accept these for use in Scotland because the submitted evidence shows clinical and cost effectiveness and acceptable short term safety. SMC does examine comparative clinical effectiveness and cost-effectiveness with medicines in use already as part of their judgement, and comparative data may be submitted; however it is the task of local ADTC to make the final judgement to introduce SMC "accepted" medicines based on local consideration of clinical benefits within the local context and the preferences of local prescribers. Access should not be judged solely on the number or value of all new medicines made available but on access to effective medicines and treatment, which will include novel medicines and many that are in use already.

One of the important roles of the ADTC (who are all represented at the SMC) is to create local formularies from all available prescription only drugs; these local decisions are agreed by hospital consultants and GPs. A formulary represents a choice of medicines, often with a preferred first choice, followed by a number of additional choices to cover the needs and clinical circumstances, of all local patients including where patients may be intolerant of a particular medicine. Formularies have general sections for use by all prescribers for commonly used medicines, and specialist sections for use by only approved specialists in that field. The formulary represents a balance of new medicines where there are improvements in effectiveness, the effectiveness of existing medicines, convenience for patients, local knowledge and familiarity with actions and side effects, and costs. Familiarity with expected and unexpected effects of medicines is critical to patient safety; the well-publicised withdrawal of a COX inhibitor anti-inflammatory medicine because excess heart attacks emerged after trials and licensing and was informed by prescribers encountering unexpected cases of heart disease.

Medicines' spending accounts for 15% of NHS budgets or about £1.4 billion each year and has risen steadily over the past 5 years. NHS Boards are accountable for managing all resources allocated to them and achieving financial balance each year. Medicines budgets have been rising steadily as NHS Boards recognise the need for new and costly medicines and an ageing population requiring treatment. Prescribing costs are funded from NHS Board baseline budgets provided by the Scottish Government and it is for NHS Boards to ensure that they effectively monitor and review the costs of prescribing within their overall funding envelope. GPs are free to prescribe any of the 12,000 licensed medicines and it is a key feature of local ADTC that GPs are engaged to prescribe responsibly. A formulary therefore

√ supports consistent good quality prescribing
√ helps patients and doctors to be familiar with the effectiveness and side effects of medicines
√ enables effective teaching
√ supports budget planning
√ enables the introduction of novel medicines in a context of knowledge and practice about local patients, existing medicines and treatments, and the assessment of new medicines in comparison to those already in use
√ promotes local ownership by GPs and hospital doctors of prescribing
√ promotes local choice of medicines for patients and prescribers.

Formularies are advisory; prescribers may prescribe legally any licensed medicine they believe to be in the best interests of a patient.

NHS Clinicians may prescribe SMC "accepted" medicines which are not on the NHS Board formulary through a straightforward "Non Formulary" request. My discussions with stakeholders did not indicate any difficulties in accessing medicines in these circumstances.

REVIEW OF ADTCs - SUMMARY OF RECOMMENDATIONS

The overall picture is one of sound arrangements for the managed introduction of new medicines within the NHS in Scotland that can be improved further. Outside the NHS there is uncertainty, lack of knowledge, and limited access to information about ADTC processes from the NHS; inside the NHS there are sound guidance and examples of excellent arrangements that are marred by inconsistency, failure to fully follow guidance and a mixed picture of availability of transparent and easily accessed information for patients and the public. My recommendations are aimed at improving these aspects.

RECOMMENDATION 1

Board ADTC should publish their local response to the SMC published advice within 30 days of the SMC advice, on the Board website and in a manner which is accessed easily by the public and patients (as required by CMO 1 2012). The response need not be definitive if further work is required but should indicate clearly the Board's intentions; the final arrangements should be published within 90 days. Members of the public involved in the work of the ADTC (drawn from the members of the Board Patient and Public Forum (PPF) can assist with describing the processes in a way that is "user-friendly" for the general public, and act as a link with the wider PPF.

RECOMMENDATION 2

Board ADTC should publish their decisions and the reasons for their decisions in respect of SMC advice to be compliant with CMO (2012)1. These reasons should include the consequences for the local formulary, even if, in the case of novel medicines, this requires further deliberation and planning. Patients and the public should be signposted from the front page of the Board website to a link which will provide information about recent SMC decisions and subsequent formulary decisions and the overall formulary should be published alongside this information and updated as required.

RECOMMENDATION 3

Board ADTC should demonstrate the engagement of their PPF in the work of the ADTC. For preference, Board ADTC should have at least one member drawn from the PPF or demonstrate the connection between the PPF and the work of the ADTC

RECOMMENDATION 4

NHS Scotland should consider a national meeting of all relevant specialists, organised by Healthcare Improvement Scotland (HIS) , to agree a national implementation plan for some new medicines accepted by the SMC that meet agreed criteria. These criteria may include the introduction of novel, first in class medicines where there is considerable uncertainty of its place in therapy. The plan will apply to all patients covered by the SMC "accepted" advice and to all Boards to support equity of access. Further, HIS should continue to audit access to new medicines and compliance with CEL 17 (2012) and SGHD/CMO (2012) 1.

RECOMMENDATION 5

NHS Scotland should retain the existing ADTC to maintain alignment of patient and GP interests, safe prescribing and enable Boards to manage their costs. Regional clinical networks could have a role in agreeing equitable access to new medicines in relation to their populations.

REVIEW OF IPTRs - SUMMARY OF RECOMMENDATIONS

RECOMMENDATION 6

All Boards should adopt the same IPTR paperwork and process, based on the examples from Greater Glasgow and Clyde, Lothian or Grampian. The application should contrast the clinical criteria appraised by the SMC where "not recommended" advice has been published with the patient's disease and personal clinical characteristics so that the reasons for the IPTR are more easily assessed, and can be audited.

RECOMMENDATION 7

The IPTR arrangements in Boards should be audited by HIS to assess compliance with guidance and its consistency of application, and to publish the results.

RECOMMENDATION 8

Clinicians should be provided with basic training and guidance in the IPTR process locally. Clinicians who are uncertain or inexperienced should be able to access specialist advice and support (see recommendation 10).

RECOMMENDATION 9

Boards should consider whether IPTR panels should include a member of the public drawn from the Board's patient and public forum. Member(s) will require training and support.

RECOMMENDATION 10

All doctors considering an IPTR must be able to access consistent, knowledgeable support for their patients. National Services Division (NSD) should establish and maintain a register of approved specialists to support IPTR. One specialist may be sufficient for orphan and ultra-orphan diseases, but more than one specialist may need to be available for more common diseases, or variants, and on a regional basis. The model of the cancer networks is an example.

RECOMMENDATION 11

The Scottish Government and Boards should produce clear and concise documentation, available on national and local websites, that explains the roles of ADTC and IPTR, how the public and patients can be involved, and provide links to the reports recommended above and for ADTC.

RECOMMENDATION 12

The RCMF should focus on access to medicines for ultra-orphan diseases. Access should be supported where the SMC has published 'not recommended' advice after a full submission of the medicine, and after a successful IPTR or GPTR has been agreed.

REVIEW OF AREA DRUGS AND THERAPEUTICS COMMITTEES

The short life working group had agreed new guidance on the function and roles of ADTC, attached as Appendix 2. However, during the course of my examination of IPTR, reading the reports of the recent Health and Sports Committee public sessions and the evidence submitted, and listening to the views of patient and public representatives, a number of further concerns about ADTC have been articulated. Healthcare Improvement Scotland (HIS) have conducted an audit of access to new medicines in NHS Boards which is attached at Appendix 3 and which provides some helpful factual information relevant to my report.

HOW WELL ARE ADTC WORKING?

SMC is admired widely for the speed of its appraisal process, but the availability of accepted medicines to local populations is viewed by patients, the industry and members of the public as very slow.

However -the Medicines Access audit conducted by Healthcare Improvement Scotland for 23 SMC "accepted" medicine decisions published between April 2012 and September 2012, indicated that the average uptake of these on to Board formularies was 74%. This suggests that the majority of SMC "accepted"medicines are made available across NHSScotland.

ADTC decisions appear to some public representatives and those that gave oral evidence to the Health and Sports Committee to be less than transparent, arbitrary, inconsistent and slow to members of the public, including industry, or patients seeking local information. This is in stark contrast to the advice of the SMC which is made publicly available together with the reasons for that advice.

CMO (2012)1 detailed 6 categories for Boards to record decision making, ranging from included on formulary through pending protocol or awaiting response from prescribers to not included. This means that Board ADTC can make decisions on new accepted for use medicines within 2 weeks of the SMC in one of these categories for each new medicine. Board ADTC decisions could be available within 30 days of the SMC recommendation, and be updated as the decision is progressed, with a final decision by 90 days. The changing status of the decision could be updated as required and the transparency and speed of the process should be available to the public and patients.

The HIS Medicines Access Audit found that there is a mixed picture of availability of easily accessed information for patients and the public and identified 7 Boards which provided easy access to ADTC decisions and access to their formularies, 3 provided more limited access and 4 had no information about ADTC or formulary. An example of internal good practice is NHS Lothian where prescribers are provided with a summary of SMC decisions and the ADTC advice for the formulary on the Board intranet and a separate formulary website - although this is not easily accessible to the public.

RECOMMENDATION 1

Board ADTC should publish their local response to the SMC published advice within 30 days of the SMC advice, on the Board website and in a manner which is accessed easily by the public and patients (as required by CMO 1 2012). The response need not be definitive if further work is required but should indicate clearly the Board's intentions; the final arrangements should be published within 90 days. Members of the public involved in the work of the ADTC (drawn from the members of the Board Patient and Public Forum (PPF) can assist with describing the processes in a way that is "user-friendly" for the general public, and act as a link with the wider PPF.

ADTCs appear to members of the public to reach different decisions in different Boards. From the public perspective, the ADTCs responses to SMC new drug advice appear to be significantly different; there appears to be little evidence available that links the published SMC advice to the evolution or development of local formularies. It is difficult to determine whether SMC advice has been considered nor are the reasons for ADTC decisions evident. CMO (2012)1 required the SMC to indicate to Boards when a new medicine represents a therapeutic advance over comparative medicines which should help with decision making locally, and that is starting to happen. For the 23 medicines described in the HIS report, the average uptake on to Board formularies was 74%. The reasons for not including the remaining 26% needs to be explored further to determine whether it reflects different local service provision or inconsistent use of the decisions categories set out in SGHD/CMO (2012) 1 (or both).

RECOMMENDATION 2

Board ADTC should publish their decisions and the reasons for their decisions in respect of SMC advice to be compliant with CMO (2012)1. These reasons should include the consequences for the local formulary, even if, in the case of novel medicines, this requires further deliberation and planning. Patients and the public should be signposted from the front page of the Board website to a link which will provide information about recent SMC decisions and subsequent formulary decisions and the overall formulary should be published alongside this information and updated as required.

Patient and public representatives told me that Board ADTC are inconsistent with respect to public involvement in their work. A few ADTC have one or two members drawn from the Board PPF. NHS Forth Valley is a good example where the PPF member contributes to the work of the ADTC and reports to the PPF. Others use public representatives on ADTC sub-committees. The advantages of involving public members include assistance with understanding the public reaction to SMC advice, support with communication of decisions to patients and the public, and consideration of the public concerns with formulary development and the introduction of new medicines.

RECOMMENDATION 3

Board ADTC should demonstrate the engagement of their PPF in the work of the ADTC. For preference, Board ADTC should have at least one member drawn from the PPF or demonstrate the connection between the PPF and the work of the ADTC.

SMC is a consortium of Board ADTCs making advice statements on the clinical and cost-effectiveness of newly licensed medicines. It has been put to me that it is not clear why SMC advice needs to be considered again with the same information by every Board ADTC.

In practice, the Western Isles, Orkney and Shetland share a formulary with Highland and Grampian respectively, Lothian and Borders work closely together, and the regional cancer, diabetes and cardiac networks deliver co-ordinated and agreed treatment clinical pathways, each covering several Health Boards. Thus many decisions are taken collectively now while retaining local ownership and governance. The HIS audit demonstrates also considerable convergence of Board ADTC decision making.

It is claimed by the ABPI that local examination of SMC "accepted" medicines results in inconsistent decisions resulting in unequal access to new medicines, and unnecessary delays citing in their written evidence to the Health and Sport Committee "further hurdles before the medicine reaches patients". The specific example cited was national consensus meetings. However further discussion about this example at the Health and Sport Committee Meeting on 18 September 2012 highlighted the complexity for the introduction of the medicine in question on the basis that; there was uncertainty about how this new medicine should be introduced in a safe and effective manner by prescribers who had never used it before. As a result, HIS convened a meeting of relevant specialists from all Boards to agree an implementation plan to ensure that patients accumulated the benefits while Boards managed the prescribing risks. There has only been one such consensus meeting and such a measure represents, in my view, and that of many consultees, good practice to ensure more uniform and equitable uptake of a new medicine for those who might benefit most, exactly countering the criticism above.

RECOMMENDATION 4

NHS Scotland should consider a national meeting of all relevant specialists, organised by Healthcare Improvement Scotland (HIS) , to agree a national implementation plan for some new medicines accepted by SMC that meet agreed criteria. These criteria may include the introduction of novel, first in class medicines where there is considerable uncertainty of its place in therapy. The plan will apply to all patients covered by the SMC "accepted" and to all Boards to support equity of access. Further, HIS should continue to audit access to new medicines and compliance with CEL 17 (2012) and SGHD/CMO (2012) 1.

The following table sets out some of the advantages and disadvantages of the current system alongside two other models; 3-5 networks or regional ADTC based around existing networks for cancer or heart disease, and a single national ADTC.

Table 1.

ADTC model	Advantages	Disadvantages	Costs
Current 14 ADTC	GPs have agreed to follow local Board formularies that they are involved in Local accountability for resources (10% of budget) Reflect patients' needs in that community Prescribers become familiar with medicines and very aware of side effects Published evidence shows that local ownership correlates with effectiveness Patients' needs and GP preferences aligned well Generics adopted rapidly by agreement	Smaller Boards could pay more for some medicines Different decisions across Scotland Access varies across Boards Variation in the introduction of novel medicines	GPs do 90% of prescribing Larger Boards cut deals with wholesalers CHPs use pricing and GP incentives to make significant drug savings in year Costs managed well locally Opportunity costs of consultant and GP time Costs reduced through generics
Network ADTC (3-5) reflecting existing networks and cross-Board referrals	Agreement across Boards for new, novel medicines, and works already in existing clinical networks May improve access for some patients New purchasing arrangements may reduce costs	Delays in getting specialty groups together High risk of GP disengagement Reduce Board and CHP flexibility	Increased transactional costs High risk of GP prescribing budgets being exceeded
Single ADTC for Scotland	Hard to distinguish from SMC Access will be delayed for all new hospital medicines but may be more uniform New purchasing arrangements to control overall costs Should improve perception of better access for all and across Scotland	Very high risk of GP disengagement with more off formulary prescribing GPs will develop practice based formularies to control costs High risk of consultant disengagement Delays in access No local accountability for medicines use Goes against published evidence on the effectiveness of local formularies	Increased costs of medicines Increased opportunity and transactional costs to Boards No flexibility at Board or CHP for managing large budget Higher opportunity costs for GPs and consultants NHS Boards unable to manage properly a significant 10% of budget

ADTC do more than maintain a local formulary of medicines based on SMC recommendations. They act as a catalyst for education in the correct use of medicines and therapeutic developments, and agree many other aspects of medicines management including intravenous medicines, special medicines for skin disease and abdominal illness, feeding supplements, antimicrobial policies based on local laboratory data as well as national policy, medicines surveillance and post marketing identification of side effects. They undertake clinical audit and monitor the compliance with local formulary. These functions are not likely to be replaced by a national body. In my view, the gains from a national ADTC are small in relation to the costs needed and the associated opportunity costs generated. Much more can be done to encourage ADTC to address the issues of variation, delay and lack of transparency as I have recommended. However the ADTC need to work smarter and harder to demonstrate that the local advantages of retaining ADTC are matched by improvements in access to new medicines and public reporting of their work.

RECOMMENDATION 5

NHS Scotland should retain the existing ADTC to maintain alignment of patient and GP interests, safe prescribing and enable Boards to manage their costs. Regional clinical networks could have a role in agreeing equitable access to new medicines in relation to their populations.

REVIEW OF INDIVIDUAL PATIENT TREATMENT REQUESTS (IPTR)

INTRODUCTION

NHS Boards are expected to follow SMC advice which is applicable for the majority of patients covered by the medicine's licensed indication. Individual Patient Treatment Requests (IPTR) were introduced in 2010 by CEL 17 (2010). The intention was to ensure that patients, who were different from those in the clinical trials or studies submitted to the SMC as evidence of clinical or cost effectiveness, could access medicines 'not recommended for use' in Scotland by SMC subject to meeting certain clinical criteria. This was a new arrangement to the older notion of 'exceptionality' and recognises that patients are not all the same and that there may be many subtypes of patients/disease that are not included in early clinical trials and submitted study data. The onus was on treating doctors to make the case to a local Panel that treatment for a particular patient was justified because they were different in a clinically significant way from the generality of patients studied in the data submitted to SMC. The patient was expected also to have a significant health gain.

Advice to NHS Boards on the implementation of CEL 17 (2010) were reinforced by SGHD/CMO (2011) 3 and CMO (2012) 1.

HOW WELL ARE IPTR WORKING?

Reading the evidence provided to the Health and Sports Committee^[3] and the Committees Official Reports^[4] suggests a mixed picture. There appears to be evidence that IPTRs have been of benefit to many patients across NHS Scotland but evidence also of dissatisfaction. Comments from the public, the pharmaceutical industry, patients, and doctors suggest wide variations in approach to the NHS Board IPTRs across Scotland.

IPTRs were described in evidence to Health and Sport Committee in December 2012, as "not the way to access medicines" not recommended by the SMC. Yet it is clear that some patients do access successfully, though an IPTR, medicines not recommended by the SMC. Much of the discussion focussed around the cost effectiveness threshold, which is a balance between clinical effectiveness and cost. The limited data available shows that there is no systematic bias against cancer drugs in either SMC or IPTR decisions.

Public

Evidence from the public representatives I met, newspaper accounts and letters shown to me demonstrate a widespread belief outside the NHS that IPTR are poorly understood and for some represent a convenient back door for any patient to access any medicines not approved for use by the SMC. The clinical nature of the justification for agreeing to the request, and the possibility of refusal, has not been fully understood, and has not been explained to patients when seeking advice.

Some public representatives have complained that information about the local implementation of new medicines is not accessible and is not written in plain, understandable language. A good example of useful and clear information is on the Health Rights Information Scotland website http://www.hris.org.uk/patient-information/information-about-health-services/access-to-new-medicines/ and is available also on the Scottish Government website. However this publication dates from 2010, doesn't mention Area Drugs and Therapeutic Committees (ADTC) or IPTR by name, nor does it give a clear picture of how these Board processes work and how a patient can be involved. Many respondents said that the information was very good but not comprehensive enough.

Pharmaceutical industry

Evidence to the Health and Sports Committee was provided by the Association of British Pharmaceutical Industry in Scotland (ABPI). The industry raised concerns about a lack of consistency and lack of information about IPTR outcomes which they believe indicates a postcode lottery to new medicines of value to selected patients but 'not recommended' by the SMC. Concerns have been expressed also about the perceived lack of access to new medicines, particularly new cancer medicines, leading to a reduction in the research access and spending in Scotland by the pharmaceutical industry. These concerns were echoed by doctors giving evidence to the Health and Sport Committee, but no data was submitted.

The Chief Scientist Office indicate that in recent years there has been a decline in traditional, large phase III commercial trials; this was in line with expectations as the UK is not able to compete on price with emerging markets in Eastern Europe, the Far East and South America. However, Scotland has emerged as a country where smaller phase II studies are placed, frequently involving less than 5 patients ,and for studies that are proving difficult to recruit in other countries. As a consequence, the number of commercial trials undertaken at sites in NHS Boards in Scotland held up at over 600 since 2010. Data on contract value from NHS Boards in Scotland suggests there has been no fall off in income for commercial studies.

Patients

Some patients' representatives have given good examples of how the IPTR process has worked for patients. However all have found the process difficult to understand and some feel unsupported throughout a lengthy and uncertain period. I was quoted examples where doctors give a clear explanation to patients and explain the reasons that they are, or are not, different in the sense required for a successful IPTR. Some patients reported however that their doctors either did not understand, or did not support an application. Reasons given to patients by their doctors included lack of experience in the using IPTR, lack of trust in the process locally, or a fatalistic assumption about the outcome. Yet the point of the new medicines arrangements was to strengthen public understanding and the doctor-patient relationship. Patients should expect a clear explanation and understanding of the benefits and harms of new medicines recommended for use and hence why they might be prescribed or not for them, and the reasons that some new medicines were not recommended and were therefore not available in NHS Scotland. The IPTR was to build upon this collaborative relationship by exploring with patients whether there were good reasons to believe that they might respond to SMC "not recommended" treatments. The reality for many patients appears to fall short of this ideal.

Patients have reported widely differing standards of patient or public involvement in the IPTR process locally, ranging from it being 'usual 'for patients to attend to no patient attending and from it being 'usual' for lay representation on the panel to no lay representation. Some patients feel they have had little opportunity to put their case in writing or in person. The existing guidance published under cover of SGHD/CMO(2011)3 is clear that where patients are able to and wish to participate, they should be given the opportunity to do so. However patients need to understand that the panel considers only clinical factors in making a decision, and attending an IPTR will not impact on the decision-making. Whilst there are confidentiality concerns about having a lay person on the IPTR panel, 2 patients reported to me that their confidence in the impartiality of the process was enhanced by having a lay person in the panel.

Doctors

Many doctors are familiar with the IPTR application and paperwork; they may regard it as a chore but accept that this is how access to SMC 'not recommended' medicines is achieved for certain patients based on clinical factors. Doctors indicated support for the IPTR concept but believed that the specialist knowledge required for a successful IPTR was not always available and that there was wide variation in the application of relevant clinical criteria. However some doctors appear to dislike the process because they believe the SMC made the wrong decision and do not believe in or understand a cost threshold based on quality adjusted life years; others do not understand fully the application process or their role clearly; others feel not supported to make a good application. Worryingly, a clinical director told me that some doctors make an application deliberately knowing that it would fail; this seems to me to be dishonest and not a substitution for an honest conversation with the patient.

It was clear to me that those doctors making more than one or two applications each year understood the application process, were supported usually by a pharmacist, had access to the relevant specialist knowledge and were successful more often than not. Doctors who apply occasionally, who lack the relevant specialist knowledge, and who are not supported well by a pharmacist believe their ability to support IPTR for their patients is impaired.

Charities

Evidence from the Health and Social Care Alliance suggested that charities based in Scotland have a good understanding of the IPTR arrangements and can support patients. Charities with their headquarters outside Scotland vary in their understanding and support to the IPTR process. Some, like Diabetes UK, with Scottish branches understand the arrangements but do not have the local resources to offer patients support in an application; those with no presence in Scotland have little understanding of the new medicines arrangements in Scotland and tend to assume that decisions made by the National Institute for Clinical Excellence (NICE) for England and Wales apply also in Scotland. Patients therefore have a mixed experience of understanding and support from medical charities.

Boards

Arrangements for IPTR vary considerably across NHS Boards. It is clear that the guidance in CEL 17 (2010); SGHD/CMO(2011)3 and SGHD/CMO(2012)1 has not been fully implemented by NHS Boards to achieve consistency of approach. The IPTR paper work is variable and completed in different ways and with different levels of detail. There is inconsistent public involvement or accountability and the involvement of patients is variable too. Training and support for doctors varies considerably, and there is considerable variation in the availability of specialist expertise. One example of good practice is found in the Cancer Centres in Glasgow and Edinburgh; here excellent support is available from senior clinicians, a pharmacist, public health and senior manager. The West and Southeast cancer networks provide excellent support to other Boards in their networks so that patients get the best advice and support wherever they live.

Board IPTR decisions are perceived, like ADTC, to be opaque and to lack accountability to local people and patients. While there are data protection issues to consider, an annual report summary of IPTR decisions across Scotland would go a long way to improving this perception and public involvement would help also with bridging a communication gulf.

RECOMMENDATION 6

All Boards should adopt the same IPTR paperwork and process, based on the examples from Greater Glasgow and Clyde, Lothian or Grampian. The application should contrast the clinical criteria appraised by the SMC where "not recommended" advice has been published with the patient's disease and personal clinical characteristics so that the reasons for the IPTR are more easily assessed, and can be audited.

RECOMMENDATION 7

The IPTR arrangements in Boards should be audited by HIS to assess compliance with guidance and its consistency of application, and to publish the results.

RECOMMENDATION 8

Clinicians should be provided with basic training and guidance in the IPTR process locally. Clinicians who are uncertain or inexperienced should be able to access specialist advice and support (see recommendation 10).

RECOMMENDATION 9

Boards should consider whether IPTR panels should include a member of the public drawn from the Board's patient and public forum. Member(s) will require training and support.

RECOMMENDATION 10

All doctors considering an IPTR must be able to access consistent, knowledgeable support for their patients. National Services Division (NSD) should establish and maintain a register of approved specialists to support IPTR. One specialist may be sufficient for orphan and ultra-orphan diseases, but more than one specialist may need to be available for more common diseases, or variants, and on a regional basis. The model of the cancer networks is an example.

RECOMMENDATION 11

The Scottish Government and Boards should produce clear and concise documentation, available on national and local websites, that explains the roles of ADTC and IPTR, how the public and patients can be involved, and provide links to the reports recommended above and for ADTC.

HOW CAN WE SUPPORT PATIENTS BETTER WITH ULTRA-ORPHAN DISEASES?

Rare Diseases UK and others raised concerns that some patients suffering from very rare diseases (known as "ultra-orphan") may never access effective treatment. Clinicians and their patients regard this as unfair. Ultra-orphan diseases are widely recognised as those occurring in less than 1,000 of the UK population (equating to <100 patients in Scotland).

The pharmaceutical industry has responded positively to European incentives offered to pharmaceutical companies to support the development and licensing of new drugs for the treatment of orphan and ultra-orphan diseases. This is in a context where such medicines will never be widely used and the cost will remain very high always and can be distinguished from other orphan medicines which will treat larger patient numbers where approval is not granted on first application because the initial cost is too high and where the cost could fall because there is a larger market for the medicine or a PAS can be agreed.

The SMC has published advice to confirm its acceptance of some medicines for orphan diseases but not generally those for ultra-orphan diseases. The Patient Access Scheme (PAS)^[5] process has contributed to the SMC's ability to accept some orphan medicines as the discount offered under the terms of the PAS improved their cost-effectiveness. meaning that such medicines are now available within the NHS in Scotland. NHS Board Chief Executives established pooled resources to share the costs and risks of funding high cost, low volume medicines for certain orphan diseases, and a limited number of other treatments e.g. recombinant blood products. The Board of residence contributes their weighted share and any excess costs are covered by the weighted contributions of other Boards to the shared risk pool. This collaborative arrangement has made the decision to provide treatment more equitable and improved access for patients from smaller NHS Boards. NHS Chief Executives exercise their accountability by regular scrutiny of the arrangement, managed on their behalf by the National Services Division (NSD) of National Services Scotland (NSS).

However, some ultra-orphan medicines are not available for NHS Scotland because no application has been made by the manufacturer to the SMC. Among the cited reasons is that there is insufficient data to support a clinical and cost effective application because of the small number of patients treated.

Other ultra-orphan medicines are not approved by SMC because of the uncertainties within the effectiveness evidence submitted or the very high cost, particularly where no PAS has been submitted. Whilst clinicians in Scotland have made IPTR applications for treatment; patient interest groups report variation in IPTR decisions being reached even where the clinical circumstances of the patients concerned appear to be very similar. These concerns add to the perception of inconsistent application of the IPTR process. This is a source of frustration and anger among patients and patient interest groups. I therefore made an interim recommendation to the Cabinet Secretary for Health and Wellbeing that additional funding should be made available to address these issues.

RARE CONDITIONS MEDICINES FUND - A RECOMMENDED APPROACH

The Cabinet Secretary for Health and Wellbeing announced on 14 January 2013, the establishment of a Rare Conditions Medicines Fund (RCMF) to cover the cost of medicines for individual patients with rare conditions following a successful new Individual Patient Treatment Request. The fund is available from 1 March 2013 for a period of 13 months^[6].

Patients with ultra-orphan conditions may be looked after by a variety of clinicians, often supported by a single specialist in Scotland or elsewhere. Applications for SMC "not recommended" ultra-orphan medicines would need to demonstrate failure to respond to current treatment, or no other alternative, as well as a significant expected clinical benefit greater than that experienced by the trial population and within a reasonable time frame.

The starting position for accessing the RCMF is where the SMC has published advice to confirm that a new medicine to treat an ultra-orphan condition has been "not recommended" for use following a full submission. Access to the Rare Conditions Medicine Fund (RCMF) recommended above would be considered following a successful IPTR application for a single patient. Where such circumstances apply to a cohort of patients, decisions regarding the need to consider Group Patient Treatment Requests (GPTR) for particular orphan medicines will be based on specialist clinical advice and agreed at a national level.

For both IPTR and GPTR, it would be essential to show that the medicine had a reasonable expectation of being clinically effective and was for an ultra-orphan disease. It is important that the process to consider the clinical circumstances for IPTR or GPTR applications is supported by the transparent and consistent assessment of the clinical context of the patient(s) by a nominated and recognised specialist in Scotland, or elsewhere. It is also important to be clear that whether or not the medicine has the potential to qualify for RCMF funding should not be a consideration of the decision-making panel.

Based on my interim advice to the Cabinet Secretary, I recommend some principles for access to RCMF funding:

• a full submission had been made to the Scottish Medicines Consortium for the orphan or highly specialist medicine;
• the request for the medicine has been subject to successful new IPTR or GPTR panel decision (i.e. the Fund will not be applied retrospectively);
• the request for the medicine's use is within its licensed indication; and
• a clinical judgement has been made that the patient (or patients) have the capacity to derive clinical benefit from the orphan medicine (with the caveat that decisions regarding the need to consider Group Patient Treatment Requests (GPTR) for particular orphan medicines will be based on specialist clinical advice and agreed at a national level).

The applications and outcomes for IPTRs funded through this mechanism should be monitored for completeness and consistency of the process by NSD. The Rare Conditions Medicines Fund should be managed by NSD on behalf of NHS Boards in a similar manner to the risk pooling arrangement described. NSD would monitor expenditure and report regularly to Chief Executives.

RECOMMENDATION 12

The RCMF should focus on access to medicines for ultra-orphan diseases. Access should be supported where the SMC has published 'not recommended' advice after a full submission of the medicine, and after a successful IPTR or GPTR has been agreed.

Prof C P Swainson, FRCPE, FRCSE (Hon), FFPHM

April 2013