IHS Global Insight Perspective | |
Significance | The United Kingdom's National Institute for Health and Clinical Excellence (NICE) has said in a draft document that Avastin in metastatic colorectal cancer is not cost effective for use on the National Health Service. |
Implications | According to NICE, various weaknesses were spotted in the manufacturer's analysis that may suggest the cost-effectiveness estimates for the drug have been underestimated. |
Outlook | This decision is only preliminary, and the drug will be re-evaluated on 28 September. Based on these discussions, a final appraisal determination will be prepared before final guidance is issued. With the earlier-announced £50-million cash injection for cancer drugs due to kick in from October, patients may in fact be able to get their hands on the drug even if a negative decision is reached in the final guidance for the drug. |
NICE Rejects Avastin Yet Again As Uncertainties Persist
The U.K. National Institute for Health and Clinical Excellence (NICE) has said in an appraisal consultation document that Avastin (bevacizumab; Roche, Switzerland) in combination with oxaliplatin and either 5-flurouracil plus folinic acid (FOLFOX) or capecitabine (XELOX) for the treatment of metastatic colorectal cancer is not cost effective. In an attempt to demonstrate the cost effectiveness of the drug, the manufacturer used a Markov model to compare Avastin plus FOLFOX-6 (B-FOLFOX-6) or Avastin plus XELOX (B-XELOX) with FOLFOX-6 and XELOX alone as a fine-line treatment option. This analysis produced base-case cost-effectiveness estimates of £84,553 (US$130,254) per quality-adjusted life year (QALY) for B-XELOX when compared with XELOX, and £92,634 per QALY gained for B-FOLFOX-6 when compared with FOLFOX-6. Included in the manufacturer's original submission was a patient-access scheme, whereby Avastin would be supplied at a fixed price of £4,000 per cycle of treatment for two-weekly cycles, and £1,200 for three-weekly cycles. The administration costs of the proposed scheme were estimated at £4 per cycle. When the patient-access scheme was taken into consideration, the incremental cost-effectiveness ratios (ICERs) associated with B-XELOX and B-FOLFOX-6 were estimated at £35,912 and £36,569 per QALY, respectively.
NICE's evidence review group (ERG) spotted various weaknesses in the original model, one of them being that clinical data used from the NO16966, randomised, control trial with XELOX and FOLFOX should not be pooled, and that patients who had received prior adjuvant therapy should be excluded from the analysis. The manufacturer was unable to provide cost-effectiveness estimates taking both of these modifications into consideration; therefore, the ERG had to make do with new analysis, whereby the data was still pooled, but those on prior adjuvant therapy excluded. This produced revised base-case ICERs of £36,354 per QALY gained for B-XELOX in comparison with XELOX, and £31,452 per QALY gained for B-FOLFOX-6 in comparison with FOLFOX-6. The ERG then went on to suggest that the utility value for the health-state first-line treatment used in the original submission should be modified from 0.77 to 0.79, as well as increasing the time per patient for operating the patient-access scheme. This further modified the ICER values to £36,494 and £31,122 for B-XELOX and B-FOLFOX-6, respectively.
The manufacturer then went on to modify the original patient-access scheme to include an additional up-front payment for each patient commencing first-line treatment with Avastin. The details of the up-front payment remain confidential; however, this additional change decreased the ICERs for B-XELOX and B-FOLFOX-6 to £29,975 and £29,604 per QALY, respectively. The appraisal consultation document is available here.
Outlook and Implications
When evaluating the final cost-effectiveness values for the Avastin combination treatments, taking into account the various modifications made to the model, NICE remained unconvinced that the manufacturer had demonstrated a robust economic case for the drug. This decision was reached despite the fact that the cost-effectiveness estimates for the drug fell within the maximum £30,000 threshold. Starting with patient-access schemes, the Department of Health, with whom the manufacturer proposed the deal, expressed reservations about what it referred to as a complex agreement that could potentially lead to higher administrative costs than those estimated by the manufacturer. One of the main sticking points highlighted by NICE is in connection with the price of oxaliplatin in the economic model. According to the consultation document, the price of £313.50 per 100 mg used in the model could be considerably less in reality, given the increasing availability of generic versions of the drug, as well as the potential variations in the price within the National Health Service. As such, the effects of the patient-access scheme could therefore be greatly diminished. Given these concerns in the context of recent reports on the difficulties of extracting value for money from patient-access schemes, it comes as little surprise that NICE has been so critical of the proposed scheme (see United Kingdom: 2 July 2010: New Report Evaluates Patient-Access Schemes for Four Oncology Drugs in U.K.). Looking at the overall economic model, NICE reiterated that some of the inputs in the model were substantially optimistic, and that the fact that plausible modifications could be applied means that the model and the ICERs generated were associated with sufficient uncertainty to trigger a negative decision on the drug. On the clinical-effectiveness side, NICE also said that Avastin did not offer a substantial enough improvement in both progression-free survival and overall survival to warrant a positive decision. Also considered was the cost effectiveness of the drug as a second-line treatment for metastatic colorectal cancer. With a base-case ICER of £103,000 per QALY gained, this option was also rejected.
Although this decision will come as a blow to many colorectal cancer patients that may have been eligible for the drug, it also comes as little surprise, given NICE's previous decision on Avastin in this indication (see United Kingdom: 24 November 2009: NICE Rejects Avastin for Treatment of Metastatic Colorectal Cancer). The drug has so far been rejected for advanced renal cell carcinoma, followed by a recent preliminary rebuff in breast cancer, despite a patient-access scheme being proposed in both cases (see United Kingdom: 26 August 2009: NICE Confirms Non-Recommendations in Renal Cell Carcinoma and United Kingdom: 9 July 2010: Roche's Breast Cancer Drug Avastin Fails to Secure Initial NICE Backing). Despite this initial negative decision, patients may seek some relief in knowing that the government is looking at both short-term and long-term strategies to improve the availability of innovative cancer drugs through the U.K. government's announcement of plans to allocate additional money to fund cancer drugs The new government has already outlined plans to make £50 million available for this purpose from October, with more long-term funding plans for cancer drugs due to be outlined by April 2011 (see United Kingdom: 28 July 2010: New Report Shows U.K. Lags Behind in Drug Usage for Some Diseases; Extra Funding Granted for Cancer Drugs). This is by no means a final decision, and a second appraisal consultation meeting is scheduled for 28 September 2010.