12th European Biosimilars Congress April 15-16, 2019 Berlin, Germany

Biography:

Anusha Patel has completed her Graduation in 2008; Masters of Pharmacy at Kings College London and Postgraduate training in various hospitals around London. Following obtaining a Diploma in Medicines Management from the London School of Pharmacy, she has specialised in Trauma and Orthopaedics Pharmacy at UHL for a number of years. She then took on a homecare role at Kettering which has evolved into the current position. She Chairs the Regional Homecare Group for the East Midlands, and is a member of the National Homecare Medicines Committee (NHMC). She also works with the East Midlands Procurement Collaborative to assist in tenders for homecare contracts.

Abstract:

Homecare is a rapidly growing market with a value circa £1.5bn. Approximately 250,000 patients are receiving medicines via the homecare route. Biosimilars offer an exciting future: Opportunity to include more value added services, improved medicine administration (e.g. injectable medicines) through nurse support and patient education, improved patient compliance through offering help lines and checking product utilisation, improved product quality by enhanced supply chain, cold chain management, stock rotation, etc, improved track and trace systems, enhanced distribution models. Switching process at KGH-Currently a total of 100 patients on therapy via the homecare route. Rheumatology switched first, then dermatology, new patients commenced Benepali 21^st march, existing patients to switch to biosimilar as a phased process from 1^st April. Actions to take: discuss possibility of using Benepali with rheumatology team at MDT meeting, identify appropriate patients, notify patients beforehand-leaflet, clinic consultation to offer switch to existing patients, consultant/nurse to notify secretary of switch and to prepare a prescription (No registration forms needed), homecare pharmacist assistance in producing prescriptions, prescription processed by pharmacy and sent to homecare provider, homecare provider receive prescription, update patient account of switching to Benepali, homecare provider to contact patient, perform a stock check and supply “Benepali Patient Kit” on first delivery. Negotiations with the CCG-Gain share with CCG Gain share further between pharmacy and rheumatology department. Savings are to be used to recruit another nurse for department to release consultant nurse led telephone consultations for those patients who need them. Barriers to overcome were mapped out beforehand and a savings tracker was monitored to manage finances. Homecare providers are in a prime position to assist with switching as we can see in the preaparations for adalimuumab biolsimilar and trusts should work with them to ensure seamless transfer.

Biography:

Wanjie Sun is a Senior Mathematical Statistician at CDER of FDA. Prior to joining FDA, she worked at GWU as a Lead Research Scientist and a PI/co-PI for over ten years, and she also worked in pharmaceutical industry for a couple of years. She has obtained her PhD in Biostatistics at GWU. She has over 40 publications in statistical, medical, and pharmacy journals.  Her research interests are in equivalence, non-inferiority, causal inference, study design, and missing data.

Abstract:

In equivalence, biosimilar, and non-inferiority studies, intent-to-treat (ITT) analysis tends to make the two treatments look similar, thereby is generally anti-conservative. The Per Protocol (PP) analysis based on completers and compliers is more able to reflect treatment differences and is usually preferred in equivalence assessment. In clinical endpoint bioequivalence studies, the current primary analysis for assessing equivalence between a generic and an innovator product is usually based on the observed per-protocol (PP) population. However, missing data and non-compliance are post-randomization intercurrent events and may introduce selection bias. Therefore, PP analysis is generally not causal. The FDA Missing Data Working Group (2016) recommended using “causal estimands of primary interest.” In this paper, we propose a principal stratification causal framework and co-primary causal estimands to test equivalence, which was one of the approaches recommended by the recently published ICH E9 (R1) addendum to address intercurrent events. We identify three conditions under which the current PP estimator is unbiased for one of the proposed co-primary causal estimands-the “Survivor Average Causal Effect” (SACE) estimand.  Simulation shows that when these three conditions are not met, the PP estimator is biased, and may inflate Type 1 error and/or change power. We also propose a tipping point sensitivity analysis to evaluate the robustness of the current PP estimator in testing equivalence when the sensitivity parameters deviate from the three identified conditions, but stay within a clinically meaningful range. Our work is the first causal equivalence assessment in equivalence studies with intercurrent events and can be applied to comparative biosimilar clinical trials and non-inferiority trials.

Recent Publications

1. Lou Y, Jones M P and Sun W (2018) Estimation of causal effects in clinical endpoint bioequivalence studies in the presence of intercurrent events: noncompliance and missing data. Journal of biopharmaceutical statistics 1-23.

2. LaVange L M and Permutt T (2016) A regulatory perspective on missing data in the aftermath of the NRC report. Statistics in Medicine 35(17):2853-2864.

3. Permutt T (2016) A taxonomy of estimands for regulatory clinical trials with discontinuations. Statistics in Medicine 35(17):2865-2875.

4. Permutt T (2016) Sensitivity analysis for missing data in regulatory submissions. Statistics in Medicine 35(17):2876-2879.

5. Sun W, Zhou L, Grosser S and Kim C (2016) A meta-analysis of missing data and non-compliance data in clinical endpoint bioequivalence studies. Statistics in Biopharmaceutical Research 8(3):334-344.