GREEN PARK COLLABORATIVE

Treatment Switching in Oncology Drug Trials

Project ReportOctober 2016

GREEN PARK COLLABORATIVE• A multi-stakeholder forum to clarify the evidence expectations of payers

– Public and private payer requirements for evidence of effectiveness and value for specific conditions and technologies

• Key participant-stakeholders in projects– Public and private payers, FDA, NIH, AHRQ, guideline developers,

professional societies, life sciences companies

• Output/Activities (depending on project)– Effectiveness guidance documents (EGDs)– High priority topic-specific workshops and webinars

• Benefits of participation– Greater transparency of decision-maker expectations (payers, HTA, guideline

developers, health systems, etc.); substantive interaction with key stakeholders; input into methods guidance and recommendations

OVERVIEW

PROBLEMTreatment switching from the control to experimental arms in a clinical trial is a common occurrence in studies of oncology drugs and has raised questions about how these trials can best be designed, managed, analyzed, and interpreted.

TREATMENTCONTROL

INITIATIVE GOAL

SOLUTION

To clarify how best to design and implement oncology drug studies in which high rate of treatment switching are expected when these studies are intended to produce evidence for consideration by payers, health technology assessment organizations, and clinical guideline developers.

OUTPUT

A guidance document that provides best practice recommendations to ensure that oncology drug trials can permit such switches and still generate scientifically valid results. It will also provide greater clarity and consistency about the expectations of key decision makers when assessing evidence from trials in which treatment switching has occurred.

APPROACHOctober 2014Bellberry CongressAdelaide, Australia

2014

2015

January – MarchLiterature review of statistical methods

April – JuneKey informant interviews

August – SeptemberDraft best practices

OctoberConvene stakeholdersBaltimore, MD

2016

MarchDraft #2 produced

April – MayOpen comment period

August Draft #3 produced

SeptemberReview by external experts

OctoberFinal document released

NovemberProject summary and video tutorial released

GPC Initiative Begins

ADVISORY COMMITTEEMEMBERS

Michael CarducciJohns Hopkins

Jim PellissierMerck

Deborah CollyarPatient Advocate in Research

Gary RosnerJohns Hopkins

Ramaswamy GovindanNational Comprehensive Cancer Network

Mona SabharwalCADTH/pCODR

Christopher HenshallConsultant

Uwe SiebertUniversity for Health Sciences, Medical Informatics and Technology

Nick LatimerUniversity of Sheffield Health Economics and Decision Science

Kylie SprostonBellberry Limited

Clare McGrathAstraZeneca

Rajeshwari SridharaCenter for Drug Evaluation and ResearchFood & Drug Administration

GUIDANCE DOCUMENT

• Builds on work that was conducted in 2014, with support from Bellberry Ltd., a national, private, non-profit based in Australia

• Developed through extensive dialogue and consultation with a broad range of experts and stakeholders, including payers, patients, clinicians, methodologists and drug companies

• Discussions took place through an in-person meeting, numerous conference calls, and extensive electronic communication

• Final document includes 18 recommendations covering five different topic areas:– Deciding How to Address Treatment Switching– Key Analytical Methods and Decision Documentation– Use of Evidence from Outside the Clinical Trial– Stakeholder Involvement in the Study Design Process– Informed Consent: Process and Content

RECOMMENDATIONS

• Section I: Deciding How to Address Treatment Switching– Recommendation 1: When Treatment Switching Should Not Be Allowed– Recommendation 2: When Treatment Switching Should Be Allowed– Recommendation 3: When It Is Uncertain Whether to Allow Treatment Switching– Recommendation 4: Treatment Switching Trigger Event

• Section 2: Key Analytical Methods and Decision Documentation– Recommendation 5: Initial Evaluation of Analytical Adjustment Methods– Recommendation 6: Designing the Trial to Maximize the Use of Potential

Adjustment Methods

– Recommendation 7: Searching for External Evidence– Recommendation 8: Contents of Protocol and Statistical Analysis Plan– Recommendation 9: Final Selection of Analytical Methods– Recommendation 10: Reporting Selection of Analytical Methods and Results

RECOMMENDATIONS

• Section 3: Use of Evidence from Outside the Clinical Trial– Recommendation 11: Fitness of External Evidence– Recommendation 12: Reporting Analyses of External Evidence to Decision

Makers

• Section 4: Stakeholder Involvement in the Study Design Process– Recommendation 13: Directly Affected Stakeholders: Patients and Clinicians– Recommendation 14: Ethical Review Boards

• Section 5: Informed Consent: Process and Content– Recommendation 16: Informed Consent Process: Two Critical Stages– Recommendation 17: Informed Consent Process: Drafting the Consent Form– Recommendation 18: Informed Consent Content

AFFILIATIONS OF PARTICIPATING STAKEHOLDERS

• NICE• FDA• Department of Health, Australian

Government• pan-Canadian Oncology Drug Review• University of Queensland• University of Leicester• Johns Hopkins University• NCCN• Johns Hopkins Medicine• University of Alberta• Brunel University London• University of Sheffield• PBAC

• University for Health Sciences, Medical Informatics, and Technology

• The University of Adelaide• University of Maryland Medical

System• Patient Advocates in Research (PAIR)• Humana• FDA Patient Representative Program• ECRI Institute• Friends of Cancer Research• EMA• MRC Biostatistics Unit, University of

Cambridge• ASCO

SUPPORT PROVIDED BY

DOWNLOAD THE GUIDANCE DOCUMENT