On March 16, 2016, the National Institute for Health and Care Excellence (NICE) approved some major changes to the UK’s Cancer Drugs Fund (CDF). The most significant of these changes is that NICE will now be evaluating all oncology drugs approved by the European Medicines Agency (EMA), including those previously funded through the CDF. Prior to this change, the CDF had independently conducted its own reviews. Now, the CDF will only serve as a funding source to be used at NICE’s discretion. This reorganization was precipitated by years of budget difficulties and numerous disagreements about the respective roles of NICE and the CDF.
NICE has started to release oncology reviews under its revised technology appraisal process, with many additional reviews in development and expected to be released in the next few months. In this post, we will discuss those reviews and what they may indicate about the future of oncology drug funding in the UK.
NICE modified the structure of its decisions for oncology drugs in response to its new role. Just as before the change, NICE will issue recommendations for routine use. Drugs that receive recommendations for routine use will be funded through traditional NHS sources. NICE can also recommend against funding, which means that a drug will not be reimbursed by the NHS at all. With the change in procedure, NICE now has a third choice: recommending a drug for temporary CDF funding.
It is important to understand that CDF funding isn’t permanent. A recommendation for CDF funding provides a company a timeframe of up to 24 months (exact time is variable and is considered on a case-by-case basis) to provide sufficient evidence for a drug’s cost-effectiveness. As such, CDF funding is reserved for cases where there is some uncertainty about a cancer drug’s cost-effectiveness. To be eligible for CDF funding, a drug must meet the following conditions:
- The incremental cost-effectiveness ratio (ICER) must have the potential to fall into an acceptable range. The acceptable range may be adjusted based on NICE’s end-of-life criteria.
- It must be possible to address the uncertainties through further data collection. The data collection period should not exceed 24 months.
- The data collected must be able to inform an update of the original NICE guidance.
NICE CDF Reviews in Progress
NICE is expected to release technology appraisal guidance reviews for six more oncology drugs before the end of 2016 (see table 2). These reviews are furthest along in NICE’s process and, therefore, contain considerable information about their evaluation histories and possible decisions. We obtained the tentative decisions from final appraisal documents (FAD) and appraisal consultation documents (ACD).
Three of the reviews were for drugs available under the old CDF process. All three received tentative negative decisions, due primarily to ICERs outside the traditional threshold. Two of the three had not previously been reviewed by NICE and did not detail any specific CDF considerations. The third was a rapid reconsideration with a tentative negative decision. What is interesting about this third rapid reconsideration is that despite the company providing a patient-access scheme (PAS), NICE did not find it plausible that the drug could be cost-effective. This may have been partially because NICE found the drug ineligible for end-of-life consideration, which would have increased the ICER threshold to 50,000 GBP.
Three more reviews were new NICE reviews (and not reconsiderations). One had a draft decision for availability under the CDF in which NICE stated that there was a high degree of uncertainty in the ICER and that the uncertainty could be resolved by further clinical data. One received a tentative negative decision in which NICE stated that it would be willing to consider the drug for CDF funding if the company could demonstrate the possibility of acceptable cost-effectiveness and provide details about a data collection plan. And the final review was not a reconsideration, did not discuss the CDF, and received a tentative negative decision.
Although a detailed analysis must wait until more data are available, there are some interesting points to note from the small selection of reviews that will be completed prior to 2017.
The reconsiderations completed to date have all resulted in positive decisions and routine NHS funding, but the outlook for the rest of the 2016 decisions is not as favorable. None of the CDF reconsiderations to date have resulted in decisions to temporarily continue funding through the CDF. Some key points about the reconsiderations include:
- Manufacturer Discounts: Discounts have played a major part in HTA decision making for quite some time. NICE’s new technology appraisal process has not changed that. All the reconsiderations to date have included confidential manufacturer discounts. The presence of a discount does not guarantee a positive decision. For example, NICE’s forthcoming review of everolimus has a tentative negative decision despite the manufacturer offering a PAS.
- Analysis of Updated Clinical Data: All the reconsiderations that resulted in positive decisions contained considerable additional analysis of updated clinical data. For example, NICE’s August 2016 reconsideration of bosutinib for Chronic Myeloid Leukemia (CML) took into consideration the changing standards of care, patient comments, unmet need, and increased clinical understanding of CML biology. NICE considered whether bosutinib was innovative and found that it “might be considered moderately innovative in a setting in which more targeted and individualized treatment may become possible in the future.”
- End-of-Life (EOL) Criteria: Whether a drug qualifies for EOL criteria will likely play a major role in determining whether a CDF reconsideration can secure routine funding or continued CDF funding. Continuing from the example above, NICE considered whether bosutinib met EOL criteria, and concluded that the drug met these criteria for accelerated and blast phase CML but not for chronic phase CML. NICE commented that these points considered together made bosutinib a cost-effective use of NHS resources. A counter example is NICE’s rapid re-evaluation for everolimus (in progress) which has resulted in a tentative negative decision. After significant consideration of the trial data, NICE found that the drug did not meet EOL criteria, which likely played a major role in the tentative negative decision.
NICE has seriously considered several new drugs/indications for CDF funding, though only one review (not yet released) has a tentative decision for CDF funding this year. The CDF historically had numerous budget issues, so one may suspect that NICE is trying its best to provide CDF funding only for drugs whose existing evidence strongly suggests the possibility for future cost-effectiveness. Several points affected these new NICE decisions:
- Maturity and Potential of Trial Data: NICE recommended against CDF funding for drugs with high ICERs and mature clinical data. They stated that since the clinical data were already mature, there was no potential to collect new data that would resolve uncertainties or reduce the ICERs in the next 24 months. Conversely, in the one review with tentative CDF funding, NICE noted that there were serious uncertainties in the data and that the clinical evidence was immature. As such, there was potential for more mature trial data to resolve uncertainties in the future.
- Timing: Two of the reviews released so far this year noted that the manufacturers did not have an opportunity to make a strong case for CDF funding. It is unclear whether further time to develop a case for CDF funding could have resulted in a different decision.
Further analysis will be necessary before we can identify definitive trends about the Cancer Drugs Fund. The CDF historically had numerous budget issues, so one may suspect that NICE is trying its best to provide CDF funding only for drugs whose existing evidence strongly suggests the possibility for future cost-effectiveness.
There remain some questions which time and further analysis may answer:
- Now that NICE is reviewing all oncology products, how will this affect the time to issue decisions?
- Given that NICE now has another avenue for funding oncology drugs, how will NICE's decisions compare to the decisions of other health technology assessment (HTA) agencies that do not have this option?
Since the research was conducted for the original blog post in late October and the publication of our post, NICE published new and updated documents. Several of the reviews mentioned in this post are/were late in NICE's process at the time of the original research. In the later stages of NICE's process, changes can occur rapidly as NICE publishes new opinions and manufacturers provide additional information. Several such changes have occurred in the short time since the writing of this particular post:
- The FAD for nivolumab was published, replacing the tentative negative decision from the ACD with a tentative positive decision.
- The FAD for everolimus was published, replacing the tentative negative decision from the ACD with a positive decision.
- The final guidance documents for cobimetinib and osimertinib were published, so these drugs are now included among the completed assessments instead of the forthcoming assessments. Osimertinib, consistent with the tentative decision in the FAD, received a decision for temporary CDF funding.
The original conclusions of the blog post remain largely unchanged. Though NICE reversed two of its tentative decisions from negative to positive, they did not recommend any further changes for CDF funding. Only one drug so far, osimertinib, has received temporary CDF funding. At least in this first round of drugs evaluated under the new process, NICE seems to prefer issuing decisions for (or against) routine NHS funding rather than providing temporary CDF funding. We will see if this changes in the future as manufacturers develop a clearer understanding of the new process and its requirements over time.
While we do not plan to update this post further, we will continue to keep a close eye on NICE and the CDF, continuing to issue new posts on any important new developments.