North-South divide?

Gaining regulatory approval for a new medicine is a significant milestone, but it is an intermediary step on the pathway to the patient's bedside. Since the inception of the National Institute for Health and Clinical Excellence (NICE) in 1999 and the Scottish Medicines Consortium (SMC) in 2002, the so-called 'fourth hurdle' to access has become firmly embedded in the UK.

Both organisations have roles that are broader than carrying out technology assessments (TAs). However, in conducting TAs, they have generally similar aims, namely to provide Primary Care Trusts (PCTs) and Health Boards (HBs), respectively, with consistent information on the cost-effectiveness of new therapies.

But do Scottish and English patients gain similar access to new medicines?

Assessing value
A comparison of the decisions of NICE and SMC, for those medicines which have been assessed as single TAs by both organisations, demonstrates that, in 82 per cent of cases, the final decisions have been broadly similar, according to data from the SMC. This implies great similarity in the assessment of value by the respective organisations. There are, however, some significant differences.

While SMC reviews all new medicines, indications and formulations launched since 2002, NICE has a topic selection process with criteria including burden of disease, cost to the NHS, policy importance and country variations. NICE also has the potential to include older therapies. Consequently, there are material differences in their work plans. For example, all oncology medicines are reviewed by both, while few treatments for rarer, and in particular 'ultra-orphan', conditions (< 1 per 50,000 population) are reviewed by NICE, the latter instead supported via the National Specialised Commissioning Group (NSCG).

The October 2009 Office of Health Economics (OHE) report, Access Mechanisms for Orphan Drugs: a Comparative Study of Selected European Countries, states that, of 28 orphan medicines (prevalence < 5 per 10,000 population) assessed by the SMC, 46 per cent were not accepted for use. NICE only reviewed two from the group, both of which were recommended. Does this reflect a difference between the value put on these therapies in Scotland versus England? Probably not. Instead, it reflects differences in the systems.

Both NICE and SMC base the TA on the incremental cost-effectiveness ratio (ICER), with the cost per quality adjusted life year (QALY) as the core metric. While there is no formal threshold, in general a product with a QALY below £20,000 (about €23,000) is likely to be accepted as cost-effective, assuming no significant limitations with the data submitted. However, most orphan medicines have relatively high uncertainty around the data estimates and high costs per QALY. Above £20,000, and certainly above £30,000 (about €34,700), NICE and SMC decision-making requires more judgement and both take broader factors into consideration.

NICE, in its 2008 Social Value Judgements report, describes the need to take into account whether the true benefit is fully captured in the QALY. For very rare diseases, it refers to the view of the NICE Citizens Council Report on Ultra Orphan Drugs of November 2004 that states: "no-one should be left behind". Consequently, by managing these conditions via the NSCG, it has accepted the case for investing in treatments bringing significant benefit to patients with very rare conditions, although this may not be cost-effective under conventional decision criteria.

SMC applies 'modifiers' to its decisions, taking account of societal and other factors, including evidence of substantial improvement in life expectancy or in quality of life, lack of other therapeutic options, possible bridging to a definitive therapy or orphan disease status. As such, treatments for high need, orphan conditions have been approved with costs per QALY potentially above £40,000 (€46,000), like mecasermin (Increlex) for growth failure in children and nelarabine (Atriance) for T-cell leukaemia. The Scottish system does, therefore, have the potential to value orphan medicines more highly although, as the OHE study shows, many such medicines will not receive a positive decision through the SMC process.

If a physician believes a patient in Scotland needs a 'not recommended' medicine, an individual patient treatment request is made to the HB. Each HB has local process and criteria for judging such requests. In high-need cases, therefore, the patient may receive the treatment. For the sake of transparency, consistency and simplicity, NHS Scotland should consider a more centralised approach for the 'ultra-orphan' group, putting less emphasis on the TA and more on other factors such as medical need.

Timing
Another key difference is timing. Historically, NICE has carried out TAs on multiple medicines treating a particular disease (MTAs), targeting completion in 14 months. In practice, this has meant that many products are in the market for a significant period before assessment, potentially leading to 'NICE blight', such as when PCTs are reluctant to provide funding until NICE has completed an evaluation. This has caused significant delays in many therapies reaching patients.

NICE introduced single TAs (STAs) in 2006, aiming for a 36-week assessment, with publication six weeks later. The faster timescale is, in part, due to the manufacturer's economic model being accepted as the base input, while in the MTA process, NICE develops its own model. Thus, the period of 'blight' is potentially reduced. However, STAs still cover the minority of medicines, and are focused initially on oncology. To date, the 36-week target is proving difficult to achieve in many cases, especially where NICE Evidence Review Groups (ERGs) modify the submitted economic model, leading to extended discussions with the submitting company.

The SMC carries out single product TAs based on the manufacturer's submission and has the shortest target timeline of 18 weeks, including publication. The SMC's 2008 Evaluation Programme Summary Report states that SMC advice was issued within six months of launch for 81 per cent of medicines subsequently 'accepted for use/restricted use' and for 65 per cent of medicines subsequently 'not recommended'.

This quick assessment is invaluable to the Scottish HBs, as it supports SMC 'shaping' medical practice close to launch, rather than trying to modify behaviour later. The SMC can move so swiftly because, although it critically appraises submissions, it does not carry out any economic modelling itself. Rather, it asks the company to do this, if required.

The advantages of a rapid review producing a decision close to launch are clear and NICE should be encouraged to move in the same direction. Given the relatively high degree of concurrence in decisions between NICE and SMC, the value of the added complexity of the NICE STA process has to be questioned.

Access
In England, the NHS is legally obliged to fund and resource medicines recommended via the TA process, thus supporting access. It is unclear, however, whether this is happening at the expense of medicines that have not been reviewed by NICE, so this is an area to watch.

In Scotland, there is no automatic link between the SMC decision and funding. Given the fact that the SMC reviews all medicines, and that budget impact and affordability are not part of that decision process, it is not unreasonable that there is no mandatory funding to follow SMC decisions. NHS Board Area Drug and Therapeutics Committees (ADTCs), which are represented on the consortium, are, however, expected to make SMC-recommended medicines, or their equivalents, available. But there is a need for increased transparency regarding local decision making processes and how 'equivalence' is determined, to support manufacturers in efficiently making their case to ADTCs.

Following a Parliamentary inquiry into access to cancer medicines, the Scottish Government issued updated guidance to NHS Boards to improve the transparency and consistency of local decision-making in mid-May. However, the fact remains that for NICE a 'yes' means 'yes' and for SMC a 'yes' means 'maybe'.

Recently, several variations to NICE processes have been introduced, some of which, like patient access schemes, have parallels in Scotland. NICE has adopted 'end of life' considerations supporting medicines which significantly extend this period and thus increase the possibility of approval, despite relatively high costs per QALY.

But where might this lead? If 'end of life' medicines are a special case, then what will be next? When the next significant treatment for a high need, chronic condition, such as stroke or dementia, is launched, potentially at a high cost per QALY, will it also be an exception? The threshold will again be open for discussion. If the list of 'exceptions' to push up the threshold increases, given limited budgets, will there be pressure to 'push it down' for lower need disease areas?

New medicines should not, however, be the main focus for TAs. Given budget constraints, both organisations should be further encouraged to evaluate all high budget, new and old interventions, medicines or otherwise. Appropriate disinvestments should be a higher priority.

NICE has increased its resources and the number of TAs conducted, but given the burden of its processes and the other options within the NHS in England, it seems unlikely that it aims to review all new medicines. However, lack of advice around time of launch can cause problems, and local drug evaluations are beginning to increase.

Since value assessments are not fundamentally different, surely it is time to increase the degree of mutual recognition, and thus efficiency, between NICE and SMC?

The Author
Frances Macdonald, PhD, is a pharmaceutical consultant and ABPI member of the SMC

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