How I set up an RCT NW Principles of QI & Research 18 th May 2015 Dr Anton Krige

How I set up an RCT

NW Principles of QI & Research18th May 2015Dr Anton Krige

El Capitan – The Worlds Hardest Climb

1st Draft Protocol

August 2011

The TERSC StudyA Case Story

NW Research Design Service.

October 2011

PPI Forum

December 2011

RfPB Submission

May 2012

RfPB Outcome.

November 2012

REC Approval

November 2013

RN appointed

November 2013

The TERSC StudyA Case Story

RfPB Contract Signed

December 2013

Start Recruitment

February 2014

Start Nested Study

November 2014

End Recruitment

March 2016

Publications!

August 2016

Project Management• Trial Design• Co-applicants &

collaborators• Grant preparation• Database design• Appoint & train

research nurse• Train staff• Trial Registry• Site File/Archiving

• Portfolio Adoption• TMG, TSC & DMEC• IRAS completion• Patient Diary, PIS,

Consent form, GP letters, SOPs, Posters

• Annual reports: DMEC, REC & RfPB

• Protocol Amendments• Additional nested

studies

Objectives

• Clinical Research Question• Literature Search• Trial Design• Protocol• Funding• Application Process & Trial Registration• Conduct• Reporting & Dissemination

UK DUETs: where Uncertainties about the Effects of Treatment are Collected & Published

https://www.library.nhs.uk/duets/



Formulating a Clinical Research Question

Objectives


Objectives


Preparatory Work

• Systematic review• Observational studies• Feasibility studies• Pilot studies

Research Design Service North West

• free advice on research design to researchers in the North West who are developing proposals for national, peer-reviewed funding competitions for applied health or social care research

• (http://www.rds-nw.nihr.ac.uk/)

http://www.rds-nw.nihr.ac.uk/

Patient & Public Involvement (PPI)

• Searchable database of completed & ongoing projects in core outcome set development

• Repository for project protocols & other documents (e.g. questionnaires),

• Maintenance of these resources in a publicly available searchable database

• Guidance on developing & reporting core outcome sets• Preparing guidance on integrating patient reported outcomes

into core outcome sets • Guidance on obtaining funding to develop core outcome sets

Specifying Target Difference

• The difference in primary outcome value the study is designed to detect reliably.

• Ideally both an “Important” (MCID by stakeholder group) & “Realistic” (~current evidence) difference.

Methods for specifying Important &/or Realistic Differences:1. Anchor 2. Distribution 3. Health economic 4. Opinion-seeking 5. Pilot study 6. Review of evidence base 7. Standardised effect size

RCT Design Alternatives

Efficacy versus Effectiveness Studies

Superiority, Non-Inferiority & Equivalence• Superiority:

– Show experimental Rx better than control Rx. – However, can’t claim Rx’s equally as good when non-significant

results.• Equivalence:

– 2 treatments could be called equivalent if observed difference & its 95% CI are completely inside the interval of clinical equivalence.

– Usually bioequivalence trials. • Non-inferiority:

– Significant result (p < 0.025) means the experimental Rx isn’t (much) worse, i.e. non-inferior to control Rx.

– Conclusion “non-inferior” depends on the chosen value for ∆NI.

When to use Non-Inferiority

• Placebo-controlled trial not ethically possible (anymore)

• E not expected to be better than C on primary efficacy end point, but is better on secondary end points or safer

• E not expected to be better than C on primary efficacy end point but is cheaper to produce or easier to administer

• E not expected to be better than C on primary efficacy end point in a clinical trial, but compliance & therefore efficacy will be better outside the clinical trial

Objectives


SPIRIT 2013 Statement:• Recommendations minimum set of scientific, ethical &

administrative elements that should be addressed in a clinical trial protocol.

• Outlines in 33-item checklist & figure.• Facilitate the drafting of protocols & improve their

completeness. • High-quality protocols can promote proper trial

implementation, reduce avoidable protocol amendments, & facilitate full appraisal of the study’s scientific & ethical considerations.

http://www.spirit-statement.org

Objectives


Grant Applications

• Target appropriate Grant• Where to find Grants?• How much time to allow?• A “Dream Team”• NIHR Portfolio Adoption

Resources

• Research Design Service – North West• North West Surgical Trials Centre• NIHR Grant Streams• Major Charities/Patient Groups• Colleges (NIAA), Associations & Specialist

Societies• Local R&D

Objectives


Trials Registries

Objectives


Clinical Trials Units (CTU)

• Statistical design & analysis• Data management & monitoring• Trial management• Information support

NIHR Clinical Research Networks

• Centralised NHS permissions – multi-centre R&D approvals

• Fund NHS research support posts - experienced "front-line" research staff

• Fund NHS support costs – Diagnostics & Pharmacy

Objectives


• Enhancing the quality and transparency of health research

• Library with comprehensive searchable database of reporting guidelines & links to other resources relevant to research reporting.

http://www.equator-network.org

Consolidated Standards of Reporting Trials:Various initiatives developed by to alleviate the problems arising from inadequate reporting of RCTs.

CONSORT Statement:• Evidence based minimum set of recommendations for reporting RCTs• Standard way for authors to prepare reports of trial findings• Facilitates complete & transparent reporting• Aids critical appraisal & interpretation

Comprises a 25-item checklist & flow diagram:• Items focus on how the trial was designed, analysed & interpreted • Flow diagram displays progress of all participants through the trial

http://www.consort-statement.org

Documents

How I set up an RCT NW Principles of QI & Research 18 th May 2015 Dr Anton Krige