This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of sorafenib according to its licensed indication for advanced hepatocellular carcinoma (HCC). The ERG report was based on the manufacturer’s submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The licensed indication for sorafenib specifies advanced HCC patients for whom locoregional intervention and surgery are unsuitable or had been unsuccessful. The clinical evidence came from a multicentre randomised controlled trial (Study of Heart and Renal Protection; SHARP) of sorafenib plus best supportive care versus placebo plus best supportive care, with 602 participants of a predominantly European ethnicity broadly comparable to the UK population. The submitted evidence indicated that for advanced HCC patients with Child–Pugh grade A liver function and relatively good Eastern Cooperative Oncology Group performance status, sorafenib on average improves overall survival by 83 days relative to placebo, and also increases time-to-radiological disease progression. Sorafenib therapy had little or no effect on time-to-symptom progression or on quality of life as measured using a disease-specific questionnaire. Sorafenib treatment was associated with increased incidence of hypertension and of gastrointestinal and dermatological problems. However, the therapy was reasonably well tolerated and, in SHARP, withdrawals from treatment due to adverse events were similar in the sorafenib and placebo arms, although more temporary reductions in dose were required in the sorafenib than in the placebo group. In the base case, the manufacturer’s submitted economic analysis generated a deterministic incremental cost-effectiveness ratio (ICER) of £64,754 per quality-adjusted life-year (QALY). The ERG extracted individual patient data for overall survival and disease progression, reran the economic model to check the submitted cost-effectiveness results, and performed new analyses which the ERG considered relevant to the decision problem; these analyses delivered ICERs between £76,000/QALY and £86,000/QALY. The guidance issued by NICE (7 May 2009) stated that sorafenib, within its licensed indication, is not recommended for the treatment of advanced (Barcelona-Clínic Liver Cancer stage C) HCC patients for whom surgical or locoregional therapies have failed or are not suitable, and people currently receiving sorafenib for the treatment of HCC should have the option to continue treatment until they and their clinician consider it appropriate to stop. Subsequently the manufacturer submitted a patient access scheme to the Department of Health. The base-case ICER submitted by the manufacturer for this scheme was £51,899/QALY. When the ERG reran the model with inputs considered relevant to the decision problem the ICER estimates ranged between £53,000 to £58,000/QALY and substantially higher values depending on the nature of the sensitivity analyses. NICE considered the impact of the patient access scheme and determined that it was not sufficient to alter the guidance.
Coverage with Evidence Development, Only in Research, Risk Sharing, or Patient Access Scheme? A Framework for Coverage Decisions
