We reviewed 43 recommendations associated with 23 cpgs evaluating 17 tts, finding that 38 recommendations (88%) supported use of the tt and that Ontario government funding was approved for 28 of them (74%). Funding approval decisions were strongly associated with cpg recommendations.
Several other important findings emerged. First, most cpg recommendations (79%) are supported by data from phase iii trials. Second, among cpg recommendations with key evidence describing comparative measures of os and dfs or pfs, the survival differences were statistically significant in 53% (16 of 30) and 81% (21 of 26) of cases respectively. Third, for more than 50% of the foregoing cases, the reported absolute difference between treatment arms was less than 3 months. Finally, although absolute effect size was not found to be associated with funding-approval decisions, we did observe a trend in association between drug funding and a statistically significant improvement in os.
In Ontario, 9 cpg treatment recommendations did not receive funding approval. Of those 9 recommendations, only 2 were related to a treatment plan associated with potentially curative intent (alemtuzumab for T-cell leukemia); both recommendations were based on single-arm phase ii studies. Among the 7 recommendations associated with noncurative intent, only 1 was associated with a statistically significant benefit in os (bevacizumab for advanced non-small-cell lung cancer); in 2 other cases, there were statistically significant improvements in pfs or time to progression (second-line trastuzumab for advanced breast cancer and tositumomab for non-Hodgkin lymphoma). The magnitude of benefit associated with the key evidence for each of those indications was modest, with median differences between the treatment arms of less than 3 months.
Two earlier studies have evaluated approval processes for new anticancer therapies in the United Kingdom and Ontario. In their review of decision-making at Christie Hospital NHS Trust (United Kingdom), Foy et al.54
described funding that was based on thresholds related to effectiveness. In a related study, Martin and colleagues55
reported that priority-setting decisions in Ontario were based largely on clinical benefit and that rationales could change with changing costs and budgets. The present comparison of funding approval status for anticancer drugs in Ontario and the United Kingdom shows that tt
s were more often approved in Ontario. Given that recommendations from nice
may place greater weight on formal economic evaluations56
and cost effectiveness, it is possible that differences in funding decisions were related to different thresholds associated with economic evaluations. Among the 13 recommendations funded in Ontario but not approved for funding by nice
(), 2 were associated with curative intent (imatinib for Philadelphia chromosome–positive acute lymphoblastic leukemia), and 1 of those 2 was based on phase iii
data demonstrating a significant improvement in os
. The other 11 recommendations were associated with noncurative intent. In 3 cases, statistically significant improvements in os
had been reported (temsirolimus and sorafenib for renal cell cancer and cetuximab for metastatic headand-neck cancer). Of the remaining 8 recommendations, 6 were associated with statistically significant improvements in pfs
or time to progression. Among the 9 therapies associated with statistically significant improvements in os
, or time to progression, the magnitude of the benefit was greater than 3 months in only 2 cases (temsirolimus for renal cell cancer and bortezomib for myeloma).
While not a study specific to oncology, work by Clement et al.
recently evaluated relationships between evidence, cpg
s, and drug funding decisions in three jurisdictions: the United Kingdom (nice
), the Australia (Australian Pharmaceutical Benefit Advisory Committee), and Canada (Canadian Common Drug Review)57
. Between 2000 and 2008, nice
recommended listing for 87% of submissions compared with 50% for the Common Drug Review and 54% for the Pharmaceutical Benefit Advisory Committee. In a related study of nice
, Mason and Drummond58
reported that, among 55 cancer therapies assessed between 2000 and 2008, 53% were ether rejected for routine use in the U.K. National Health Service (5 of 38, 13%) or restricted to a narrow set of indications (15 of 38, 39%). Those authors also observed a trend toward more negative decisions in recent years. In another report written with colleagues59
, the same authors compared cancer drug therapy approval decisions in the United States and the United Kingdom and concluded that drug coverage decisions that include processes to consider cost-effectiveness (such as those made by nice
) are associated with greater restrictions and slower times to coverage.
The present study is the first comprehensive evaluation of the relationship between evidence, cpg
s, and funding approval decisions for anticancer drugs, but the results should be interpreted in the context of study limitations. Drug-funding approval processes in Ontario have recently changed. As of October 2011, a national advisory committee [the pan-Canadian Oncology Drug Review (http://www.pcodr.ca
)] has begun issuing funding recommendations to participating provincial ministries of health and the existing Ontario subcommittee of the ced
. Accordingly, our conclusions may not be generalizable to future funding approval processes in Ontario or to guideline programs or funding agencies in other jurisdictions. Our study may also include more specific limitations based on our hierarchical framework for identifying key evidence (including prioritizing articles over abstracts) and a relatively small sample size of tt
recommendations that likely precluded an ability to identify statistically significant findings. In only a single case (sorafenib for hepatocellular carcinoma) was a published phase ii
study prioritized over a conference abstract of a randomized controlled trial. Furthermore, our analyses do not take into account cases in which more than one published phase iii
randomized controlled trial might support a tt
. To be able to explore how effect size is related to funding decisions, we needed to identify treatment effects. We chose a 3-month threshold for that analysis because we felt that most patients and clinicians would agree that 3 months is clinically significant, and others authors have suggested the same magnitude of effect. We compared drug funding statuses between Ontario and nice
in the United Kingdom. However, in the United Kingdom, local Cancer Drug Funds can provide funding for cancer therapies that are not approved for funding by nice
. Accordingly, it is possible that, at the local level in the United Kingdom, there is less discordance in funding status for cancer therapies than our results would suggest. Finally, we did not independently evaluate pharmacoeconomic aspects of treatment, and we suspect that, given the substantial costs of many new drugs7
, pharmacoeconomic analyses, including those provided in reports by nice
and those performed but not widely reported in Ontario evaluations, may account for the differences observed.