Response to NICE consultation document on Social Value Judgements

June 2005

The NICE consultation of April 2005 recognises that social value judgements are an integral part of the evaluation process for high-cost therapies. The Society for Endocrinology has reviewed the document (the consultation paper), in conjunction with the Guide to Methods of Technology Appraisal (the guide), which defines the process and economic methods that NICE adopts, and which also includes important social value judgements. The Society has a number of significant concerns that it wishes to have taken into consideration in the revision of the document.

Endocrine diseases

The subject of endocrinology comprises a wide range of diseases of the hormone and metabolic systems. There are several high-profile, high-incidence endocrine diseases, such as diabetes, thyroid disease, obesity and osteoporosis. However, there are also many rare endocrine diseases that fall within the legally established EU definition of rare diseases, ie an incidence of less than 1 person per 20001. These include acromegaly, Cushings, MEN 1 and 2, congenital adrenal hyperplasia, Addison’s disease, and many others. Some may also fall within the ultra rare definition used by NICE. The preferred definition of rare diseases is that already embedded in UK and European law.

Many endocrine diseases are chronic – once contracted, they can be managed, but not cured, and the patient will need medical care throughout life. If untreated, many lead to increased mortality as well as morbidity2. Many are commonly diagnosed either during childhood (eg GH deficiency, craniopharyngioma) or in relatively early adulthood (eg acromegaly, Cushings). This means that many endocrine patients must live with a debilitating condition for many decades, often for the rest of their lives. The time profile of intervention and costs, and clinical benefit, is very different from acute medicine.

Additionally, untreated endocrine disease increases the risk of other illnesses such as diabetes, cancer and heart disease, which are government priorities for prevention.

The Society for Endocrinology’s view on the NICE value judgement methodology

Chronic, incurable, lifelong diseases such as many endocrine conditions must be assessed, and the patient experience judged, differently from acute diseases such as cancer.

Ethical principles

The Society does not have the resources to secure specialist ethical advice. However, some issues are clear to us. The principle that NHS funds should not be wasted on ineffectual treatments is accepted. The general principle of ‘opportunity cost’ is accepted, but we believe the consultation paper should set this in a factual context of recent downward trends in branded drug costs3 following the 2005 the Pharmaceutical Price Regulation Scheme negotiation, and NICE’s own estimate in 2004 that its positive decisions account for 0.1% of NHS costs4. The Society has always acknowledged the high cost of some endocrine therapies and clinical members have been very conservative in prescribing these, far more so than in some other Western countries. The consultation paper should acknowledge this proper self-discipline explicitly.

The consultation paper acknowledges widespread ongoing differences of view on the ethical foundations of care, and we would suggest that this divergence requires a far more cautious approach to potentially restrictive decisions if these would exclude patients entirely from clinically effective treatments, if NICE is to secure widespread acceptance for its processes. The recent Alzheimers draft FAD is an example of such a restrictive decision.

We note that it appears that, of the variety of ethical perspectives listed, the QALY-based appraisal methodology as detailed in the guide is essentially based on the utilitarian view constrained by certain rules, such as Recommendations 7-10 in the consultation paper. The ethical basis should be made clearer.

Specific areas of concern

The Society now has considerable practical experience of the QALY methodology used by NICE. It has come to believe that aspects of this are flawed and the practical application is not always consistent with the stated values or with the principles set out in NICE’s Establishment Orders

The fundamental difference between assessing chronic, as opposed to acute, disease is the main focus of the Society for Endocrinology’s concerns in relation to the NICE methodology and value judgements. This was shown clearly by the results of the judgements on adult GH deficiency5 and the draft FAD for drugs for the treatment of Alzheimer’s disease6, where groups of clearly diagnosed patients have been left without treatment or subject to very restrictive criteria. This difference has a number of implications and the Society for Endocrinology contends that:

  1. The NICE QALY-based methodology may be suited to assessing varying treatments for acute medical conditions, but it becomes very unsatisfactory for chronic conditions, where a small increase in quality of life (QoL) may be very important over many decades. Treatments for patients with chronic diseases often give modest incremental increases in quality of life. However, for a patient who has to live with a debilitating and distressing condition for the rest of their life, and also for their carers, relations and friends, this relatively small improvement in QoL may be extremely important. The economic methodology does not weight for this, as NICE has rejected equity weighting. We nonetheless believe that methods need to be adopted that will reflect this central concern. We would be happy to discuss further potential methodologies.
  2. Following on from this, the point made in Recommendation 6 that age discrimination is acceptable where “age is an indication of risk or benefit” seems to us to imply equity-weighting on the basis of life-long conditions. The Society for Endocrinology would agree with the consultation document that, for chronic conditions which are often diagnosed relatively early in life, the increased risk of not treating over many decades (eg heart disease, diabetes, increased mortality) and the added benefit of treating in terms of improved mortality, morbidity and quality of life over several decades, indicate that age discrimination in favour of the younger patient is appropriate. However, this has not been used in the previous appraisals with which we have been involved, notably the adult GH appraisal.
  3. Whilst it is entirely reasonable to compare the cost-effectiveness of alternative treatments and for the NHS to focus its resources on the treatments for a particular disease that offer the best combination of cost and benefit, patients with chronic conditions should never be denied all available treatments where there are effective treatments available.
  4. Although NICE is empowered to be flexible, our experience has been that the £30,000 /QALY threshold has been applied tightly by the Appraisal Committee. This experience suggests that Recommendation 4 in the consultation paper has not been followed in practice. NICE needs to ensure its committees follow its principles.
  5. Chronic disease has major implications for the QoL of the prime carers and other family members of patients, in many cases also for the rest of their lives, and it is essential that this is taken into account in the cost-effectiveness studies. The reference case7 is inadequate in this respect and does not meet the requirement to consider “the broad [our emphasis] balance of benefits and costs”8 because it excludes the impact on carers and families. Equally, an improved QoL for a chronic disease sufferer will reduce the dependence of patient and carers on other social services and this should be taken into account in a system that is supposed to involve ‘joined-up’ government.
  6. For rare diseases the evidence base may be limited. Patients should not be penalised because there are inadequate double-blind placebo-controlled trials to provide data to NICE’s preferred requirements, as the NHS does not routinely fund these. This is especially important for therapies that were licensed before the advent of NICE, when such trials were not a requirement. Such trials cannot normally be carried out retrospectively, as ethical clearance would not be given for depriving control patients of a licensed treatment that has proven efficacy. The Appraisal Committee needs additional guidance on acceptable evidence when sources are limited, as will usually be the case for rare diseases, and the evidence of clinical specialists should be given particular weight in these appraisals.
  7. In the case of existing therapies where there is no likelihood of funding for adequate new trials (although one could contend that NICE should arrange funding where it is the body that requires the results), one of the main bodies of evidence is that of the patients and carers. This could be analysed effectively, but, apart from a few notable cases such as the Alzheimer’s Society9, the patient support groups do not have the resources to carry out such research themselves. NICE should fund such research, and give significant and formal weight to the results. Equally, patient groups have to put substantial resources into their input into NICE assessments, which has major opportunity costs for such groups and is arguably not where the donors expect to see their money used. This requires adequate support from public funds.
  8. NICE’s insistence on cost-effectiveness studies is likely to divert limited resources away from studies that would seek to move forward the boundaries of clinical science.
  9. NICE is creating an environment which could be seen as hostile to research and development of new therapies, many of which introduce incremental benefits in chronic disease and which are bound to be expensive initially due to the small numbers involved.

Conclusions

  1. The NICE methodology needs to be amended significantly to handle chronic diseases satisfactorily, as opposed to acute diseases.
  2. The principle of inclusiveness should underpin all NICE’s work. Therefore, while it is reasonable to compare a range of potential therapies on the basis of cost-effectiveness, no patient should be left with no treatment where there is an effective treatment available.
  3. NICE is not obliged to be constrained rigidly by QALY calculations; it is empowered to be flexible. Moreover, there is a precedent for NICE to use other methodologies than QALY calculations and also to recommend therapies with a QALY of more than £30,00010. Where the QALY calculation introduces false premises as outlined above, it should not be used as the sole, or probably even the main, indicator.
  4. We believe a further draft of this important document should be circulated for comment before it is formally approved.


Appendix – supporting notes

  1. The use of incremental cost-effectiveness ratios (ICERs) is more suited to analysing acute diseases, rather than chronic diseases. For cancer, for example, the 5-year survival rate gives an endpoint that relates directly to the “output” of treatment in QALYs. In contrast, it is not possible to establish accurate estimates for lifetime increased health related quality of life (HRQL) from a new treatment for chronic disease where the benefit is expected, but cannot be proved, to continue many decades in the future. Treatment has to be based on reasonable clinical endpoints, and the lifetime cost effectiveness estimates will always have a very wide measure of uncertainty. This is confirmed by some of the huge variations seen in a study on acromegaly11. If only a short time horizon is used, as was the case in the GH appraisal, it will exclude the important effect of reduced life expectancy and age-related comorbidity. These economic methods do not create new clinical information, and are not robust enough to bear the weight that is put on them.
  2. The methodology does not allow for the effect of the patent premium in new drug prices. This premium is how society funds research and introduction of new therapies. The long-run opportunity cost (factor cost) of manufacture is typically very much less. The NICE analyses use current NHS procurement costs and, as NICE focuses on expensive therapies, this will normally be the cost during the limited patent window. Most expensive therapies will become very substantially cheaper over time and, in assessing therapies for chronic disease, this has a very substantial effect on the cost-benefit outcome.
  3. The use of discount rates for QALYs is very controversial. The idea that a year’s good health should be valued by society differently at different points in time seems intrinsically implausible. We thus consider the use of discounting in most circumstances for chronic disease flawed in principle. A non-endocrine example illustrates the principle. A preventive therapy such as the new cervical cancer vaccination, with a 30+ year wait for the benefit, would have its benefit halved if discounted at 3.5% (the current NICE rate) over those 30 years. This would be likely to introduce a major hurdle to what must by any measure of common sense be seen as an important and necessary new preventive therapy. Many endocrine conditions have a similar ‘preventive’ time profile, eg lifetime treatments for acromegaly effectively give patients 9.5 years of extra (good quality) life.
  4. We have been advised that NICE uses static, rather than dynamic modelling. This does not allow for changes in technologies, the economic base etc, and reduces the calculation of QALYs to a theoretical, rather than a practically usable, level. This is particularly relevant for chronic disease, where the cost base will often change dramatically over time.

Notes and references

  1. The European definition of rare disease is 1 per 2000 persons. Orphanet http://www.orpha.net lists recognised rare diseases.
  2. The reduction in life expectancy for patients within the Society’s large acromegaly database was 9.5 years, consistent with other published studies
  3. IMS, quoted in The Times, 6 June 2005, p 36
  4. Andrew Dillon, quoted on BBC News 22 July, commenting on Maynard et al “Challenges for the National Institute for Clinical Excellence” in BMJ 2004; 329: 227-229
  5. Final Appraisal Determination on human growth hormone (somatropin) in adults with growth hormone deficiency, 2 May 2003
  6. Appraisal Consultation Document: Alzheimer’s disease - donepezil, rivastigmine, galantamine and memantine (review), 1 M arch 2005
  7. Guide, para 5.3.1
  8. Consultation paper, para 3.2.2.
  9. Quoted in “Drugs for the treatment of Alzheimer’s disease”, Alzheimer’s Society, May 2005
  10. Consultation paper para 4.3
  11. Moore D, Meads C, Roberts L, Song F. The effectiveness and cost-effectiveness of somatostatin analogues in the treatment of acromegaly. Birmingham: West Midlands Health Technology Assessment Collaboration, Department of Public Health and Epidemiology, University of Birmingham (WMHTAC), 2002:81.