The NICE STA process was introduced in 2005, with the intention of producing speedier guidance, especially for cancer medication. Our analysis shows that the introduction of the NICE STA process has resulted in speedier guidance but not for cancer drugs. There are some differences in recommendations between NICE and SMC, with SMC rejecting a great proportion of the drugs appraised by both organisations—20% versus 10%.
Reason for difference in recommendations
The reasons for different recommendations might be expected to include:
- NICE sometimes allowed cost per QALY exceeding the upper bound of its cost-effectiveness threshold (£30 000 per QALY); especially after the ‘end-of-life’ additional guidance was adopted. However, in several instances, NICE did not report their estimated cost per QALY. SMC can also accept a cost per QALY over £30 000 but seems not to do so to the same extent as NICE.
- Different timings, sometimes by years, during which time ‘patient access schemes’, with part-funding by manufacturers, were introduced into NICE calculations.
- The modelling from the manufacturer was sometimes different. For example, SMC considered telbivudine to be cost-effective compared to entecavir for the treatment of chronic hepatitis B, but the manufacturer's submission to NICE did not include entecavir.
- Evolution of evidence base.
- Longer appraisals provide more opportunities to explore subgroups. Therefore, differences may arise between decisions if one organisation has time to evaluate numerous subgroups within a population.
- The difference in timelines means that if a drug is rejected by SMC, the manufacturer may be able to revise the modelling before the drug goes to NICE.
Reasons for lengthier NICE appraisals
The causes for the lengthier process at NICE include consultation
7 and transparency. NICE produces a considerably more detailed report and explanation of how the decision was reached. Publically available material includes drafts and final scopes, responses by consultees and commentators and a detailed final appraisal determination. Our impression (two of us have been associated with NICE appraisal for many years) is that the length of the Appraisal Consultation Decisions and Final Appraisal Determination has increased over the years. More recently, we have noted that drugs may be considered more often by the appraisal committee than the expected two times—there are examples of drugs going to three and four meetings. In the STA process, NICE may issue a ‘minded no’ and give the manufacturer more than the usual interval in which to respond with further submissions. This in turn sometimes leads to the Evidence Review Group asking for more time to consider the new submissions. Hence, drugs may received very detailed consideration, but at a time cost.
Marked variability throughout the years () is most likely caused by small numbers, especially in 2010, where only three STAs are included. Excluding 2010, there has been a general trend for shortening STA times and lengthier MTA times. This is unsurprising, since more complex appraisals would be assessed in an MTA. The longest appraisals (77 months for etanercept in psoriatic arthritis and 60 months for infliximab for ankylosing spondylitis) are explained by the fact that NICE can appraise older drugs if referred by the DH. Both of these were appraised in an MTA with other drugs.
SMC publishes considerably fewer details. NICE appraisal committees deal with two to three STAs per day, allowing for both public and private sessions. SMC is able to deal with six to seven new drugs per day. NICE allows a 2-month period between appraisal committee meetings, 1 month for consultation and then a period for the evidence review group and the NICE secretariat to reflect on these comments and produce a commentary for the second meeting of the appraisal committee. Comments on the draft guidance (the Appraisal Consultation Decision) come from manufacturers (of drug and comparators), clinical groups such as Royal Colleges, NHS staff, patients and the general public through the consultation facility on the NICE website. and (e-version) demonstrate the pathway of appraisal for SMC and NICE.
There is a trade-off between consultation and timeliness. The emphasis by NICE on wide consultation, compared to the less extensive approach by SMC, may simply be a function of size of territory. SMC and its New Drugs Committee have representatives from most health boards. (Note that in Scotland, trusts have been abolished and NHS boards are unitary authorities providing both primary and secondary care, so representatives include managers and clinicians). This in effect allows consultation as part of the process, though mainly with NHS staff rather than patients and public. Patient interest groups have the opportunity to submit written comments to the SMC in support of a new medicine. In contrast, NICE serves a population >10 times the size, and it would not be possible for every Primary Care Trust or trust to be represented on the appraisal committees.
The wide consultation by NICE may reduce the risk of legal challenge. NICE is probably more likely to be challenged than SMC for two reasons. First, NICE guidance is used more as a reference for pricing negotiations by other countries. Second, NICE guidance is fixed for (usually) 3 years, whereas a manufacturer whose medicine has not been recommended can re-submit to SMC at any time.
Consultation by NICE starts well before the actual appraisal, with scoping meetings, and even a consultation on who should be consulted. After the scoping process, NICE makes a recommendation to the DH as to whether a drug should be appraised. The DH then decides on whether or not to formally refer the drug to NICE. This process takes about 3 months (from scoping meeting to formal referral). However, this consultation and referral process usually happens before marketing authorisation and so is unlikely to be relevant to the timelines examined in this paper. Sir Michael Rawlins, chair of NICE, has suggested that for NICE to produce guidance within 6 months of marketing authorisation, it needs to begin the appraisal process about 15 months before anticipated launch.
8 In contrast, SMC just looks at all new drugs, so no selection process is needed. This also has the advantage of complete clarity for industry since they know that if they are taking a medicine through the European licensing process, then (when successful) they will definitely be expected to provide a submission by SMC so they can plan for this at an early stage, whereas at that stage, they may not know whether it will be referred to NICE.
Reasons for lengthier appraisal for cancer drugs
One possible explanation for longer timelines for cancer drugs is that many are expensive and hence costs per QALY may be more likely to be on the border of affordability. Another possibility may be that the evidence base for new cancer drugs is limited at the time of appraisal, so the cost per QALY may be more uncertain. This represents a challenge to the appraisal committee, for example, trying to identify subgroups and stopping/starting rules. Additional analysis may be sought from the Evidence Review Group or the manufacturer. All this generates delay.
Strengths and weaknesses
We included only drugs assessed through the technology appraisal programme at NICE and will have missed a few appraised through the guideline process.
9 Appraisal outcomes were collected from published tables on the NICE website or SMC annual reports.
One problem is the definition of restricted. We have mentioned above the pimecrolimus example, which is defined as ‘recommended’ by NICE but for very restricted use. Many drugs are recommended by NICE and SMC for use in specialist care only, but this would probably not be regarded as ‘restricted use’ by most people. On other occasions, NICE has approved drugs for narrower use than the licensed indications. For example, liraglutide and exenatide are licensed for use in dual therapy, but NICE has recommended them for use only in triple therapy, albeit with a very few exceptions in dual therapy. Other examples include restriction on the grounds of prior treatment, fitness states and blood glucose levels.
If we adopted a broader definition of restricted, then one could argue that the majority of NICE approvals are for restricted use.
How does this compare to other studies
Only a few studies have looked at the differences between NICE, SMC and the impact of the new STA system.
7 10 11 In 2007, Dear
et al found a different outcome in five out of 35 comparable decisions (14.3%), with an average of 12 months difference between SMC and NICE.
8 In 2008, Barham
11 reported that the interval between marketing authorisation and guidance publication was longer for cancer STAs than MTAs.
Dear
et al also compared time differences between SMC and NICE in 2007.
10 Based on 35 drugs, they estimated the time difference between SMC and NICE to be 12 months. Our results show the difference to be closer to 17 months based on 88 comparable medications; however, when looking at only STAs, this was approximately 12 months. Dear
et al also found an acceptance rate of 64% by SMC, although this does not take into account re-submissions. Our data show an acceptance rate of about 80%, which probably reflects our use of only final SMC decisions, some after re-submissions.
Barbieri and colleagues (2009) reviewed decisions on 25 cases where NICE and SMC guidances could be compared and found general agreement in terms of recommendations for use in 23 cases.
7 However, they noted that NICE was sometimes more restrictive than SMC, for example, recommending that use be limited to subgroups based on age or failure of previous treatment. They give an example, alendronate for osteoporosis, approved without restriction by SMC but restricted to age and risk status subgroups by NICE. In this case, the appraisal was done under the previous NICE MTA process involving an independent assessment report by an academic group. Barbieri and colleagues also noted that the interval between SMC and NICE appraisals could be as long as 2 years, which could lead to different decisions because of an increasing evidence base.
Mason and colleagues (2010)
12 reported that for the period 2004–2008, the STA process had not shortened the timelines compared to MTAs, for cancer drugs, but did not examine non-cancer medications. They also examined time to coverage in the USA and noted that within cancer therapy, hormonal drugs became available faster than chemotherapy drugs, which were in turn faster than biological agents. However, timelines varied among US providers such as Veterans Affairs and Regence.
Barbieri and colleagues (2009) also reviewed the role of independent third party assessment and concluded that it had advantages but that it tended to take longer, as found in this study for non-cancer drugs.
7 However, they argued that the third party system, as was provided to NICE by the academic groups, need not prolong the timelines. Indeed, they suggested that basing the appraisal on manufacturers' submissions might lead to delays if there had to be an iterative process of requesting further data or analyses.
How many bodies does the UK need to evaluate new drugs?
In addition to NICE and SMC, there are systems in Wales and Northern Ireland. The All Wales Medicines Strategy Group evaluates new medicines for the NHS in Wales. However, it aims to avoid duplication with NICE, though it may produce interim advice pending a NICE appraisal, and only assesses up to 32 new medicines a year.
In Northern Ireland, there has been since 2006 a system whereby NICE guidance is assessed for suitability for implementation in the Province, with the expectation that is normally will be adopted.
13 There is also a Regional Group on Specialist Medicines, which can issue advice on drugs not appraised by NICE.
The existence of the several bodies making policy on new drugs reflects the impact of devolution and separate development of the NHS in the four territories of the UK.
Licensing is now carried out on a Europe—wide basis but that is more of a technical judgement of efficacy and safety. Health technology assessment of new medicines takes into account a wider range of factors such as willingness and ability to pay for the benefits accrued locally, definition of value, accountability to local parliaments, local clinician buy-in and clinical guidelines.
Conclusions
The introduction of the NICE STA system has been associated with reduced time to publication of guidance for non-cancer drugs, but for cancer drugs, the STA timelines are little different from MTA timelines.
Significant differences remain in timescales between SMC and NICE. There are also some differences in guidances between the organisations, but the differences in terms of approved/not approved are often minor, such as approved for very restricted use/not approved.
1 Norman Waugh,2 Pawana Sharma,3 Mark Sculpher,4 and Andrew Walker5
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