The Evolving Role of the Statistician in Clinical Research

Dr Elisa Young

About me• Education:

• BSc (Med Lab Sci)• PhD (Pharmacology)• MSc (Statistics)

• Career: (>10 years) • Statistician, Project Management, Laboratory Management,

Diagnostic Laboratory Scientist, R&D Scientist• Novotech (2 years)

• Statistical lead and statistical programmer on over 30 studies

Disclaimer• This presentation represents my

thoughts and perspectives, based on my experience.

• Perspectives are based on working for a CRO with a small-scale statistics team and may not be representative of other CROs, nor pharmaceutical companies.

Hot Topic

Agenda

• How does the statistician fit into a clinical study team?• How does the statistician contribute during each of the study stages?• How can an organisation get added-value from statisticians?

Study Team

Project Manager Sponsor Medical

Monitor

Site Staff CRAsData Manager

StatisticianMedical Writer

Quality Assurance

Regulatory Associate

CTAs

Business Development

Human Resources

Study Stages

Plan

ning

Star

t-Up

Mai

nten

ance

Inte

rim A

naly

ses &

Data

Mon

itorin

g

Com

mitt

ees

End

of S

tudy

&

Repo

rting

• Advise on study designs• Statistical approach• Endpoints• Schedule of events

• Sample size and power calculations

Planning

Bioequivalence • High Variable Drugs• Bayesian statistics• Pharmacodynamic endpoints• Clinical endpoints

Start-Up• Protocol writing/review• Randomisation• Case Report Form (CRF) review• Consistency Check Specifications (CSS)

review

RandomizationStatic: Assigns treatment in a sequence established prior to any patients entering the study.

Dynamic: Generates random treatment assignments based on the stratification levels of the patients that have entered the trial as well as the patient entering the study.

Maintenance• Statistical Analysis Plan (SAP)• Mocks/Shells• SAS programming of Listing, Table

and Figure (TLFs, LTFs, LTGs, TLGs)

Risk Based Monitoring• Driven by “key risk indicators”• Review of statistical data over the course of the trial• Very broad range of metrics to be monitored• May involve complex modelling to estimate overall

risk and unveil data patterns• Ownership and responsibilities?

Data Monitoring Committees and Interim Analyses

• Includes: FDA safety reports, SRCs, DSMBs, IAs ……

• Varying purposes: Safety, efficacy, dose selection, sample size re-estimation, futility

• Responsibilities:• Organising provision of study output• Committee member• Statistical risk assessments

End of Study Analysis• SAS programming• Validation and QC review• Interpretation• Reporting

SAS ProgrammingCTMS

eDC

Randomisation

Safety Laboratory

PK/Immunogenicity

PD

Other….

SAS Dataset Library

Derived Datasets

Listings

Tables

Figures

CDISC Datasets

Transport Datasets

CDISC• Clinical data standards for submission of databases

and supporting documentation to regulatory bodies• To become mandatory in the next few years.• Primary responsibilities statisticians &

programmers• Entirely new work processes• Entirely new skillset• Significant affects on timelines, budgets & resources

REPORTING• Statistical Analysis Report• Clinical Study Report

• In-text tables• Section 14 (Tables & Figures)• Section 16 (Appendices – Listings)

• Manuscripts, conference abstracts, presentations

Getting the most out of your statistician/programmers

• Data Management Programmingo Data transposition for easier reviewo Identify protocol deviations and eligibility

violationso Complex data review

• Comparing old and refreshed data• Merging data from several sources• Reconcile CRF data with external vendor data

(e.g. laboratory results, randomisation data, PK data)

• Cross-study analyses• Combine/compare similar studies• Site performance

• Organisational statistics• Training

Getting the most out of your statistician/programmers

Summary

Keep us involvedAsk us questionsAsk more of us

Thank YouElisa YoungBiostatisticianNovotech Pty LtdElisa.young@novotech-cro.com