EXECUTIVE SUMMARY

  1.  Delays by NICE in identifying and assessing novel treatments is adding further to preventing UK patients from access to effective treatment.

  2.  Orphan drugs are being disadvantaged by the NICR process because the remit of NICE is structured in such a way that conventional cost effective thresholds act as a barrier due to higher per patient and incremental costs of orphan medicine. The quality thresholds should be re-evaluated for these rare disease.

  3.  A clinical specialist in the field under assessment should be involved at the initiation of the process and throughout the evaluation of the drug to ensure that the public and the profession retains confidence in the Institute.

  4.  Clinical trial design should be re-evaluated to ensure that appropriate evidence is presented to NICE by facilitating closer interaction between the Institute and clinicians before drugs come to market.

  Multiple myeloma has an incidence of four to five per 100,000 of the population and is defined internationally as an orphan drug. In the course of the last 50 years, the treatment of myeloma has been advanced, initially by the discovery of Melphalan as a chemotherapy agent in the early 1960s and then in the 1980s and 1990s by the identification of high dose combination chemotherapy with the addition of an autologous stem cell transplant for haemopoetic support. A third advance has been discovery of novel agents that has evolved from our greater understanding of the biology of the disease. Currently, there is one drug with a licence namely Velcade and a second drug that is looking for an EMEA licence in the second or third quarter of this year, namely Revlimid. In addition there are some 30+ novel agents that are in early stages of clinical and pre-clinical development. These agents are working through an entirely different mechanism of action to conventional chemotherapy and represents a major advance in the management of myeloma and indeed other malignancies. At the present time, patients in the UK are being denied access to theses agents due to the NICE evaluation process, disadvantaging rarer cancers and the speed with which the process is undertaken.

NICE PROCESS

  1.  Because of the rarity of orphan diseases, large randomised phase III trials are not able to be conducted in timely manner and NICE will only accept evidence from phase III trials. This policy needs to be revisited for orphan disease.

  2.  Property confidence in the institute is waning because "expert" clinical advice to the committee is only sought at a late stage in the process and there is a feeling that the committee decision making occurs ahead of any in put from specialists in the particular area under consideration.

  3.  NICE's decision process lags behind clinical progress and the scope of application needs to reflect current and possibly future use of the drug. This was highlighted in the evaluation of Velcade where its use as a single agent was brought into question at a time when clinicians are using the drug in combination with steroid plus or minus other chemotherapy agents which has had a dramatic effect on responses and time to progression and survival. Because this was outside the scope of the NICE review, evidence for its use in this setting was not considered and was major reason for the NICE provisional findings being challenged and confidence in the system being undermined.

  4.  It is clear that patients with rare diseases have poor outcomes following NICE reviews than in any non-orphan conditions. Review of the NICE process has shown a biased outcome against orphan drugs as has evidenced by the working paper of the OHE and a review of the NICE website. The latter has shown that six drugs, where there was a preliminary decision available in January 2007 for orphan drugs in development, none of the six agents was recommended for use as per licensed indication. This suggests either a failure on the part of the clinicians to conduct appropriate clinical trials, which identical to those conducted for non-orphan drugs or alternatively, to look at the process by which NICE conducts its approval process for orphan drugs. A major issue for the latter is the evaluation of the cost effectiveness (QALY) thresholds. Consideration should be given to changing the threshold for orphan drugs in line for what is currently identified as "super orphan" drugs. This latter appeared to be arbitrarily defined without regard to conventionally epidemiological criteria or referenced to international agreed standards. Implementation of NICE guidance is very often delayed and patchy throughout the country. This is due to the fact that Trusts, in particular Foundation Trusts, feel they are under no obligation to use these agents and a further process needs to be undertaken locally through PCTs, cancer networks and Trust's formulary and/or clinical directorate budgetary committees. All of these further delay the prescribing of drugs to patients.

Dr Stephen Schey

Chairman, UK Myeloma Forum

March 2007