A multi-center evaluation of clinical pathways cost and time using real-life data in patients treated for their breast cancer in day sessions Comparison between two modes of administration of trastuzumab: IntraVeinous (IV) versus SubCutaneous (SC) Nadia Bahmad, ROCHE 2nd World Congress on Health Economics Policy & Outcomes Research - June 29-30, 2017 Madrid, Spain 1

1 2 3 4 Contents Context and objectives Real-life data collection Comparative analyses : IV versus SC 4 Discussions

1. Context and objectives

The 2 objectives of the study Assess the organizational impacts of IV versus SC Evaluate the difference in pharmacy preparation time between the 2 forms Evaluate the difference in patient’s admission duration between the two forms (B) Assess the economic impact of IV versus SC Evaluate the differences in consumables costs for the preparation and the administration between the two forms Note: The economic perspective is from the health facility point of view.

2. Real-life data collection

Data collection methodology An observational and multicenter study with 2 forms 9 facilities Facility form: the organizational model 1 form by facility Number of patients Opening hours Pharmacy organization Herceptin® preparation 2) Patient form: the care management 1 form by patient All stages of cancer Treated with Herceptin® SC or IV Anonymous forms Details of the care process Validation by a board of medical experts: September 2016 Collection period: from mid-Nov. 2016 to mid-December 2016 (= 1 month) Patient selection: non-random method in incoming patients Theoretical minimum number of patients per facility: 15 IV and 15 SC

Data collection results An observational and multicentric study 417 patient forms were obtained 411 patients* 248 patient forms with SC 245 SC patients 169 patient forms with IV 167 IV patients** PATIENTS IV form * 6 patients came twice for a drug administration ** 1 patient received Herceptin® in a IV form, then in SC form THE 9 FACILITIES 8 out of 9 : more than 30 patient forms collected 3 out of 9 : less than 15 IV patient forms (including 1 facility with none) 2 out of 9 : less than 10 IV patient forms

A precision about cost evaluation Each medical facility performs a detailed cost analysis of consumables Illustration : most commonly used consomables For each item : unit cost and used quantity Advantages of this cost evaluation : a robust comparison (compared to “times”)  Robustness, since not influenced by factors (organization, size)  No bias of data collection among the facilities  Easily repeatable in new facilities Type of consumables for the administration of Herceptin® (SC or IV) Drip set Site Y perfuser Syringe 30 ml luer lock for preparation 0,408 Secure Hubert needle Rinse aid of 50 ml NaCl 0.9% 10 ml luer lock syringe for preparation Needle for SC 23g Disconnection set NaCl 250 ml Needle 18g for preparation 3 way luer lock faucet Secure administration device (Duoperf)

3. Comparative analyses : IV versus SC

Patient characteristics 1/6 Patient characteristics 60 (± 13) 58 (± 14) 59 (± 13) Age 66 kg (± 13) 68 kg (± 16) 67 kg (± 14) Weight (kg) Weight

Analyses of treatment combinations 2/6 Analyses of treatment combinations Monotherapy or in combination? Monotherapy in combination with another IV treatment Conclusion : The proportion of Herceptin® alone in monotherapy is significantly higher for the SC form than for the IV form.

Analyses of treatment preparation 3/6 Analyses of treatment preparation Level of anticipation (= early preparation) Anticipated Partially anticipated No anticipation Conclusion : The anticipation of Herceptin® preparation is significantly associated with the form of administration of Herceptin® (SC / IV) at the 5% threshold. Early preparation rate (before arrival of the patient) is more important for the IV form than the SC form.

Analyses of treatment preparation 4/6 Analyses of treatment preparation Preparation time 1 min (± 1) 14 min (± 12) Time (minutes) Conclusion : Average preparation times were significantly different at the 5% threshold between the SC and IV groups (p <0.0001). The mean time for pharmaceutical preparation was significantly higher of 13 minutes (± 7 minutes) for the IV form.

Analysis of total session time 5/6 Analysis of total session time Elapsed time between start and end of Herceptin® administration: IV versus SC 87% of IV patients spend more than 2 hours Probability 26% of SC patients spend more than 2 hours Time (hours) Conclusion : Average difference in administration time is 107 minutes (± 8 minutes). SC form: 74% of sessions last less than 2 hours versus 13% for IV form.

Cost of consumables : a robust comparison 6/6 Cost of consumables : a robust comparison 12.42€ (± 2.20€) Total cost (euros) 1.35€ (± 0.47€) Costs not incl. VAT Note: For 121 sessions out of 417 (29%), no consumable cost could be calculated Conclusions : A significant difference between the two forms : differential of 11.07€ (± 1.36 € VAT not included).

4. Discussions

Review of this study on the administration of trastuzumab A multicenter study: 9 facilities 411 patients were included: 60% SC and 40% IV Mean time of care admission is significantly higher by 1h47 minutes (± 1h20) for the IV form compared to SC Average time is 8 minutes higher for the installation step in SC. Average time is 40 minutes higher for the administration step in IV. Consumables cost analyses: A strong significant difference between the two forms Cost is 1.35€ for SC versus 12.42 for IV : 11.07€ of difference

Discussions Bias and limits Bias of data collection: the major role of “forms“ The matching of post-confounding factors: recruitment using a non-random method:  Strong impact of the treatment combinations (monotherapy, adjuvant, associated): 89% of SC sessions are monotherapy versus 39% of IV sessions  Unbalanced distribution of the number of patients in each group (1 month of data collection) Still, a robust and repeatable cost analysis.

Thank you for your attention. Any question?