Impact of pCODR on Cancer Drug Funding Decisions CADTH Symposium 2016 April 11, 2016 Amirrtha Srikanthan, Helen Mai, Nianda Penner, Eitan Amir, Andreas Laupacis, Mona Sabharwal, Kelvin K.W. Chan

Presenter Disclosures Fellowship financial support via an educational grant from the Ontario Drug Policy Research Network - There are regional differences (i.e., not all provinces are created equally – different sizes, different processes, different resources, and different patient population) - pCODR provided a mechanism to offer evidence-based information to all participating provinces to enable more consistent funding decisions (i.e., level playing field)

The national landscape prior to pCODR Differences in structures and processes for drug review and funding of cancer drugs Variation in use/acceptability of pharmaco-economic information, submission requirements, who could submit Variation in coverage across jurisdictions Can it be better? Drug review process is important for ensuring access to effective and cost-effective drugs Concern re lack of transparency, inefficiency with duplication of effort, limited pool of experts Pre 2007 – separate provincial review process There are regional differences (i.e., not all provinces are created equally – different sizes, different processes, different resources, and different patient population) Differences in structures and processes for drug review and funding of cancer drugs – the differences in funding channels and mechanisms is where the story starts, then the resultant review processes or lack thereof Variation in use/acceptability of pharmaco-economic information, submission requirements – and also who could submit, with many western provinces not allowing manufacturers to be officially involved and funding requests only being forwarded by tumour group (self-selection) - pCODR provided a mechanism to offer evidence-based information to all participating provinces to enable more consistent funding decisions (i.e., level playing field)

What was done? 2007 – iJODR formed An interim process Not a formal structure Provinces (other than ON) were observers not active participants No obligation to follow recommendations or timing of work An evaluative process 2011 – pCODR formed National, formalized transparent process Resources for rigorous evidence-based review Reduce duplication of review of same drug Interprovincial collaboration thought possible due to similarity in governance and accountability structures (i.e. provincial cancer systems), such as cancer agencies No obligation to follow recommendations or timing of work, which meant continued unfair access Conference of Deputy Ministers of Health in 2010 approved creation of permanent body July 2011 – first review - 9 provinces except Quebec

So what? Has pCODR made a difference? Our aims: Describe changes in concordance of decisions across participating provinces Describe changes in time from Health Canada Notice of Compliance (NOC) to drug funding across provinces Conducted a retrospective review with the support of the pCODR provincial advisory group, provincial Ministries of Health and Cancer Agencies and Health Canada Health Canada market authorization

How did we assess this? Included chemical entities with an original (i.e. first) NOC date from 2003 to May 31, 2014 inclusive Drug funding decisions and dates from 2003 – 2014 inclusive (as at December 31, 2014) Statistical analyses: Agreement statistics to assess concordance Multiple linear model to assess time to funding Quantile regression to assess differential impact Make this first point clearer – not possible to link individual indication to specific NOC date for all drugs pre 2003 3 coauthors to create list; used Health Canada Drug Product Database Online Query tool 2 separate provincial data extractions – funded, not funded, under provincial consideration, under review Used Drug Product Database and assistance of Health Canada -Provinces assistance to collect drug funding dates and decision Analysis anonymized

What drugs did we include? 2211 Indications Identified 1505 Duplicate entries 476 First NOC Date pre-2003 120 Non-oncologic Indications 22 Discontinued Drugs   88 Indications Included

Baseline Characteristics of Distinct Drugs Reviewed July 2011 – pCODR June 2011 and prior – pre-pCODR -iJODR period for the 60 drugs were not all reviewed by iJODR

Provincial Agreement in Funding Decisions This result will not change greatly 1 = total positive correlation; 0 = no correlation Two provinces (6 and 8) did not have data for all 88 indications available at the time of data collection. Missing data  pre-pCODR period and intravenously administered drugs   62 and 59 of 88 “No centralized process of record keeping” Brennan-Prediger kappa: pre-pCODR 0.55, 95% CI 0.44 – 0.66, post-pCODR 0.98, 95% CI 0.94 – 1.00, p-value<0.001   Brennan-Prediger kappa: pre-pCODR 0.54, 95% CI 0.43 – 0.65 versus post-pCODR 0.78, 95% CI 0.68 – 0.89, p-value=0.002

After censoring of missing data: pre-pCODR: 52 indications 14 (27%) had funded unanimously 5 (10%) had unanimously not funded After pCODR: 36 indications 19 (53%) were funded unanimously 2 (6%) were unanimously not funded Proportion of unanimous decisions has increased pre-pCODR 37% versus pCODR 60%, p=0.048 Unanimous – refers to when data is present, not that all 9 provinces had the data With exploratory – unanimous pre-pCODR 38% versus pCODR 94%, p<0.001

When taking into consideration indications still in the review process or under consideration No statistically significant change in the proportion of drugs funded at a provincial level pre-pCODR 66% versus pCODR 73%, p-value=0.10 - 1 outlier province removed pre-pCODR: 52 indications 58 – 85% funded After pCODR: 36 indications 50 – 72% funded

Interaction testing confirmed that the effect of pCODR on reduction of time to funding is not uniformly affecting all provinces (p=0.01). Exploratory analyses excluding provinces 6 and 8 demonstrated no change in results (the mean reduction in time from NOC date to funding date was from 752 to 489 days, for a reduction of 263 days, 95% CI 40-446, p-value=0.005) and similar interaction effect Interaction Effect: Effect of pCODR on reduction of time to funding is not uniformly affecting all provinces (p=0.01)

Time to funding analyses Nationwide, median number of days 522 to 393 days, p-value<0.001 Negative time to funding values 50 in the pre-pCODR period 2 in the pCODR period Max timelines pre-pCODR: 1355-3602 days pCODR: 749-1555 days Challenges: Incomplete data for funding dates (80%) NOC which remained present in exploratory analyses excluding province 6 and 8 (587 to 432 days, p-value<0.001). Negative: 737 with funding data 792 Total possible data set Large variations observed across all the provinces Extremes of values more likely for provinces with limited data availability Funded 456; date 357; 80z

Reduction in days, based on quantile Increase Reduction | Change in Days The blue line represents the median reduction in days demonstrated at each quantile level of submissions. Blue shading represents the 95% confidence interval for reduction. Establishment of pCODR had most influence on submissions that tend to take relatively longer to fund traditionally 75th percentile (submissions that tended to have relatively longer time to fund)  143 days reduced 25th percentile (submissions with relatively shorter time to fund)  0 days reduction Quantiles of Time to Decision Making

Summary of Conclusions Standardization of review has led to: Increased concordance in decisions across provinces No change in proportion funded Decrease in time to funding timelines Still several months Now have real transparency and conscientious decision with evidence based review – more consistent data from the pCODR period Still room for improvements

Limitations Lack of complete data sets Lack of dates Unknown rationale for discordance Lack of access to drug costs 1)Lack of complete data – unable to make full inter-provincial comparisons 2) Lack of funding status dates and submission dates limited our time to funding analyses. In particular, most funding status dates available were for positive funding decisions 3) Rationale for discordance – Systematic identification and rationale for discordant funding decisions can help tailor strategies to improve equal access throughout Canada 4) Lack of drug costs and cost-effective analyses - at the time of funding decisions prevented our ability to evaluate the association between cost and funding decisions and economic impact assessments on provinces; unknown if if there have been improvements in managing drug costs --> increase in affordability Lack of data reflective of lack of resources

Discussion Points Negative time intervals Prolonged time to funding intervals (>3 years) Ongoing inter-provincial variation Improved availability of data Collaboration (pan-Canadian Pharmaceutical Alliance) Negative – practice of approving drugs if pre-existing NOC for another indication; overwhelming clinical need for new indication; expanded eligibility not considered in original submission Prolonged – manufacturer negotiations In terms of explanation for some of the prolonged timelines, these may include: o   Funding from date of NOC, sometimes due to not being brought forward by provincial tumour groups until much later or manufacturer not making the submission until later or resubmissions o   Pre-pCODR some tumour groups wouldn’t even put forth a review that would not get funded o   Different committees and review processes were in place to manage submissions Variation – reflective of differential resources (funding, people, specialists, ability to do reviews) -Consider noting that while there are regional differences (i.e., not all provinces are created equally – different sizes, different processes, different resources, and different patient population) and that pCODR provided a mechanism to offer evidence-based information to all participating provinces to enable more consistent funding decisions (i.e., level playing field) -prepCODR variation – some provinces didn’t bother putting forward review as knew it wouldn’t get funded so why bother with the workload (under resourced) pan-Canadian Pharmaceutical Alliance as on option to help off-set drug costs – inter-provincial/territorial effort - working together to achieve greater value for brand name and generic drugs for publicly funded drug programs -conducts joint provincial/territorial negotiations for brand name drugs in Canada to achieve greater value for publicly funded drug programs and patients. All brand name drugs coming forward for funding through the national review processes, such as pCODR are now considered for negotiation through the PCPA

Acknowledgements pCODR Provincial Advisory Group Provincial Ministries of Health and Cancer Agencies Health Canada ODPRN Program Specific Individuals Helen Mai Nianda Penner Mona Sabharwal Eitan Amir Andreas Laupacis Kelvin Chan

Contact: Amirrtha Srikanthan, MD Thank you! ??? Contact: Amirrtha Srikanthan, MD amirrtha.srikanthan@bccancer.bc.ca

Appendix

Missing data  for these three provinces were all from the pre-pCODR period and were predominantly for intravenously administered drugs. Does not account for IV drugs that may be funded by hospital Two provinces (6 and 8) did not have data for all 88 indications available at the time of data collection. Missing data  for   these two provinces were all from the pre-pCODR period and were predominantly for intravenously administered drugs  Suggest specifically indicating how much data were missing   No centralized process – funded by individual hospitals – no way to access the data.   “No centralized process of record keeping” During the pCODR period, the majority of provinces had relatively similar proportions of funded drugs except for one outlier (province 7). Excluding the outlier, the proportion of drugs funded prior to pCODR varied between 58% to 85%. After pCODR, the proportion of drugs funded varied between 50% to 72%.

Indications funded prior to the NOC date occurred for drugs that were already on the market for a pre-existing indication Also, during iJODR period. If that’s the case, we may want to make it clear that the submission date was based on submissions made to Ontario 88*9 = 792 indications With funding data 88*7 + 62 + 59 = 737 With funding dates 185 + 182 = 367 Not funded: 209 Funded: 456 With dates 367/456 = 80%