1. Estimation of drug cost avoidance (DCA) and pathology cost avoidance (PCA) through participation in NCIC clinical trials group phase III trials Patricia A. Tang, Annette E. Hay, Christopher J. O’Callaghan, Nicole Mittmann, Carole Chambers, Joseph L. Pater, Natasha B. Leighl

2. Background Cost avoidance occurs when trial participation leads to provision of: –drug therapy (drug cost avoidance- DCA) –Pathology test (pathology cost avoidance – PCA) Thus, payment for standard treatment or testing is not required. The aim of this study was to estimate the total DCA and PCA for Canadian patients enrolled in NCIC-CTG phase III trials

3. Methods Phase III clinical trials that completed accrual and resulted in DCA or PCA were identified (1999- 2011) PCA was calculated based on the number of patients screened and test cost DCA was estimated based on the number of patients randomized, protocol dosing regimen, drug cost, median dose intensity, and median duration of therapy –Historical prices were used if available CA for Canadian patients accrued are presented in Canadian dollars with no adjustment for inflation

4. Results 4 trials lead to PCA 17 trials lead to DCA Excluded trials: –60 trials did not lead to PCA or DCA –36 trials: observation was the control arm –2 trials: Canadian patients enrolled was 3 or less

5. Results – Pathology Cost Avoidance TrialPathology Test Number of tests Cost of one test ($) Pathology Cost Avoidance ($) CO20KRAS33429899,395 CRC3MSI6230018,600 CRC5KRAS14029841,663 MAC1221 gene recurrence score 94342794,035,191 Costs are rounded to nearest dollar Total Pathology Cost Avoidance: $4,194,849

6. Results – Drug Cost Avoidance Targeted Therapy TrialTrial design (Drug supplied by trial) Drug with cost avoidance Mean DCA per patient ($) Total DCA for trial ($) CO20 Cetuximab Cetuximab + brivanib Cetuximab 22,5887,544,519 CRC5 Chemo + bevacizumab Chemo + cetuximab Chemo + bev + Cetuximab Bevacizumab 17,4301,115,520 MA31 Taxane + trastuzumab Taxane + lapatinib Trastuzumab 31,7841,239,595 REC1 Interferon α Interferon α + bevacizumab Interferon α 4,2906,8643 LY12 Rituximab + DHAP Rituximab + GDP Rituximab 6,1161,932,498 Total Targeted Therapy DCA = $11,900,775

7. Results – Drug Cost Avoidance TrialTrial designDrug with cost avoidance Mean DCA per patient ($) Total DCA for trial ($) MA27 Anastrazole Exemestane Anastrazole 7,3179,519,856 MAC1 CMF or AC Capecitabine CMF/AC 5356,959 MAC4 Tamoxifen Tamoxifen + OFS Exemestane + OFS Tamoxifen 44721,000 MAC5 Tamoxifen + OFS Exemestane + OFS Tamoxifen 44739,319 MAC7 Anastrazole Anastrazole + Fulvestrant Anastrazole 2,00588,209 HN6 Cisplatin + RT Panitumumab + RT Cisplatin 9014,391 BRC.3 Cisplatin + etoposide Cisplatin +irinotecan etoposide 1,1064,423

8. Results – Drug Cost Avoidance TrialTrial designDrug with cost avoidance Mean DCA per patient ($) Total DCA for trial ($) CO13 IFL FOLFOX IROX Irinotecan 10,5651,595,249 CRC2 FOLFOX FOLFOX + cetuximab Oxaliplatin 13,6653,689,425 PA2 FUFA Gemcitabine FUFA 933,993 OV16 Carboplatin + paclitaxel x 8 Cisplatin+ topotecan x 4 then carbo/paclitaxel x 4 paclitaxel 3,011710,586 OV17 Carboplatin + paclitaxel x6 Carboplatin + PLD x6 paclitaxel 4,996169,858 LY12 Rituximab + DHAP Rituximab + GDP Cytarabine 1,088171,914

9. Drug cost avoidance across trials

10. Results Across 17 trials, total drug cost savings estimated at $27,935,957 –$8,744 DCA per patient –42% Targeted therapy: $11,900,775 (5 trials) Combined pathology and drug cost avoidance: $32,130,806

11. Limitations Drug wastage, expired drug lots, published prices Regional differences in the ‘payer’: patient versus provincial health care system versus private insurance Some pathology tests may have been done as part of standard of care, prior to enrollment in the trial For some situations, there is more than one ‘standard’ eg. Tam-AI switch Utilized drug administration data, did not account for patient non-adherence

12. Conclusions Over the time period studied, these NCIC-CTG trials resulted in total cost avoidance (pathology plus drug) of approximately $7514 per patient Not all trials lead to cost avoidance These savings should be accounted for when considering the financial impact of clinical research

13. Discussion This study did not incorporate the incremental patient care costs associated with clinical trial participation

14. Liniker et al evaluated treatment cost difference for standard patient care compared to participation in industry as well as non-industry cancer trials 1 An overall treatment cost saving of £388 719 in 2009 and £496 556 in 2010 was observed, largely attributable to DCA 1 British journal of cancer. 2013;109(8):2051-7.