Estimands and Sensitivity Analysis in Clinical Trials

Crowne Plaza London Heathrow, Stockley Rd, West Drayton UB7 9NA

Presented by Rob Hemmings, Frank Petavy, Christine Fletcher, Frank Bretz

• Rob Hemmings is a partner at Consilium Salmonson and Hemmings. He was formally the manager of the statisticians and pharmacokineticists at MHRA; a member of the EMA’s CHMP and chair of the EMA’s SAWP. 
• Frank Pétavy is Head of Biostatistics and Methodology Support at the European Medicines Agency. He contributes to the provision of scientific advice for drug development and the assessment of marketing authorisation applications across therapeutic areas.
• Chrissie Fletcher is the Global Therapeutic Head of Biostatistics for Cardiovascular, Metabolic, Neuroscience, Bone, Inflammation and Nephrology, the European Regional Biostatistics Head and leads an HTA Biostatistics group at Amgen.
• Frank Bretz is Global Head of the Statistical Methodology and Consulting group at Novartis. He has supported the methodological development in various areas of drug development, including dose-finding, multiple comparisons, and adaptive designs.

About the course: 

Defining the primary objective of a clinical trial in a precise way to reflect the presence of non-compliance or non-adherence to treatment is crucial for the choice of design, the choice of statistical analysis and the interpretation of the results. This raises the need for a structured framework to specify the primary estimand (i.e. "what is to be estimated"). This is also reflected by the decision of the International Council on Harmonization (ICH) to amend its E9 guidance by discussing estimands and their role in clinical trials. The draft ICH E9 addendum on estimands and sensitivity analysis was released back in July 2017 and is being finalised while considering more than 1000 comments. All stakeholders are gaining the necessary experience and familiarity with estimands along with the associated challenges and methodologies. In this course we provide an in-depth review of the estimand framework as laid out by the draft ICH E9 addendum and present case studies illustrating the implementation of this framework in clinical trials.

The following topics will be covered:

• Introduction and motivation for the ICH E9 addendum
  - Understanding treatment effects 
  - Scope of the addendum to ICH E9
  - Motivating examples
  - Introduce a generic example to be a thread along the training course
• A framework to align planning, design, conduct, analysis and interpretation
  - A new framework for clinical trials
  - Alignment between trial objective, design, planning, conduct, analysis and interpretation
  - Implications on design and conduct of clinical trials and in the performance of statistical analyses
  - How this framework can improve discussions between sponsors and regulators on the suitability of designs and the interpretation of results
• Description, strategies and construction of estimands
  - Attributes that together describe an estimand
  - Strategies for addressing intercurrent events
  - General considerations for the construction of estimands
  - Therapeutic and experimental considerations for the construction of estimands
• Generic example and case studies (Part 1)
  - Generic example to illustrate the thinking process that aligns estimands and sensitivity analyses with trial objectives 
  - Case studies in specific disease settings: envisage a variety of options at the end of Day 1 and reconvene in the morning of Day 2 to select the preferred option(s)
• Impact on trial design and conduct
  - Implications on design and conduct of clinical trials and in the performance of statistical analyses
  - Identification of estimand(s) at the design stage requires informed discussion with all stakeholders
  - Certain estimands may require or benefit from non-standard designs and/or endpoints
• Impact on trial analysis with focus on sensitivity analysis
  - Role and choice of sensitivity analysis and supplementary analysis in light of the estimand framework
  - Main estimation, sensitivity analysis, role and choice of sensitivity analysis, supplementary analysis
• Documenting estimands and sensitivity analysis
  - Impact of the addendum on protocol writing, study design, data analysis and interpretation
  - Incorporating estimands in the writing of a trial protocol and statistical analysis plan
  - Potential impact of the ICH E9 addendum on study conduct, data analysis and interpretation
• Generic example and case studies (Part 2)
  - Use examples to review the impact of using the estimand framework on study design and data collection; on the choice of estimation methods and sensitivity analysis 

Registration

	Early Bird (Up To & Including 24th April)	After 24th April
PSI Member	£495 + VAT	£595 + VAT
Non-Member	£570 + VAT (This includes PSI membership for 2019)	£670 + VAT (This includes PSI membership for 2019)

Please click here to register.

Registration costs include lunch and refreshments. PSI are holding a limited number of hotel rooms on 21st and 22nd May which will be allocated on a first come first served basis. Please contact psi@mci-group.com to reserve a room. Rooms are charged at £109.00 inc VAT per room including breakfast.