Clinical Research and the Importance of Collaboration www. phri .ca - - PowerPoint PPT Presentation

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Clinical Research and the Importance of Collaboration www. phri .ca - - PowerPoint PPT Presentation

Mar 31, 2024 344 likes •581 views

Clinical Research and the Importance of Collaboration www. phri .ca Picture if you can..1993 www. phri .ca HOPE A large, simple, trial N Pts N Sites N Countries In the beginning ( 1993 ) 6,500 130 10 and then (1994) 8,000 160 15

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Clinical Research and the Importance of Collaboration

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Picture if you can..1993

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HOPE – A large, simple, trial

N Pts N Sites N Countries In the beginning (1993) 6,500 130 10 But finally (1995) 9,541 267 19 …and then (1994) 8,000 160 15

Collaboration!

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Study Drug Indication HOPE Ramipril Prevention of MI, Stroke & death RESOLVD Cand/Metop Heart failure OASIS-4 Clopidogrel Acute Coronary Syndrome OASIS-5 Fondaparinux Non-ST Elevation MI OASIS-6 Fondaparinux ST Elevation MI ONTARGET/TRANSCEND Telimisartan Prevention of CVD RELY Dabigatran Prevention of stroke in Atrial Fibrillation AVERROES Apixaban Prevention of stroke in Atrial Fibrillation

(Some of) the studies that followed

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Key characteristics of (most) PHRI studies

  • Scientifically interesting question
  • Collaborate with National Leaders:
  • Expert trialists’ and not just key opinion leaders
  • Member of the Steering Committee
  • Involved in developing protocol, CRFs, study procedures
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How can the process be improved?

Common issues plaguing study conduct

  • Individual case safety reporting
  • Event adjudication
  • Excessive monitoring
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Streamlining: Safety Reporting

  • First studies to use the triple “and” - serious

and unexpected and associated

  • National Leaders defend approach:
  • Locally (ethics)
  • Nationally (regulatory bodies)
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Streamlining: Adjudication

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Event Adjudication

  • No effect on study outcomes/conclusions
  • Is it worthwhile? How can we streamline?
  • Use event definitions that closely resemble usual

practice

  • Only adjudicate those events which don’t meet

the criteria

  • Ask National Leaders to adjudicate (in local

language)

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Streamlining: Monitoring

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Monitoring

  • Risk based approach
  • Used in APOLLO (2011), HOPE-3, TIPS-3 and COMPASS
  • Implemented through National Leader’s office
  • ADAMON study (2017) showed risk-based monitoring was

non-inferior to extensive monitoring

  • At best, on site may reduce major GCP findings by 8%
  • Congruent with recent ICH E6 R2 (revision)
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Collaborating to resolve fundamental clinical trial issues

2007 – Duke, Oxford and PHRI organize the first Sensible Guidelines meeting

  • Academics, regulators, industry sponsors invited
  • Objective is to identify biggest barriers to trial conduct
  • 8 publications

2009, 2012 Repeat Workshops 2017 ICH E6 modified

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Which led to other initiatives

  • Initiatives to Streamline Clinical Trials – Canada
  • India – Efforts with DCGI
  • MoreTrials (http://moretrials.net)
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Collaboration: Low & middle income countries

  • INTERHEART, INTERSTROKE, INTERBLEED
  • PURE (~180,000)
  • IMPI (Investigation of the Management of Pericarditis)
  • No effective treatment for TB pericarditis: Anti-

inflammatory may work

  • Collaboration with University of Cape Town, Bongani

Mayosi, Mpiko Ntsekhe

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IMPI Tuberculous Pericarditis Trial

RECRUITMENT BY COUNTRY

90 133 23 26 62 29 23 1014

N

Total N = 1400

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Collaboration: Low & middle income countries

  • Interheart, Interstroke, Interbleed
  • PURE (~180,000)
  • IMPI
  • TIPS-3 (The Indian Polycap Study -3)
  • Polycap in those at moderate risk of CV

disease

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Randomization

1000 2000 3000 4000 5000 6000 N Participants Canada Colombia Malaysia Tanzania Bangladesh Tunisia Indonesia

India Philippines

N=5,713

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Collaboration: Low & middle income countries

  • Interheart, Interstroke, Interbleed
  • PURE (~180,000)
  • IMPI
  • TIPS-3
  • OSCAIL: Organized Stroke Care Across Income

Levels

  • South Africa, Rwanda, India (Uganda, Sri

Lanka, Nigeria)

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Key Performance Indicators (Tool Kit)

Initial assessment, diagnosis & documentation Physiological management (FeSS) (fever, sugar, swallowing) Bowel & bladder Pressure care Anti-hrombotics Multidisciplinary teamwork Mobilization Secondary prevention (AF, lipids) Management ICH Discharge planning & caregiver involvement

Change from a usual frequency of 5-12% (based on INTERSTROKE) to over 25% in each country (i.e. at least one in four patients)

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Rwanda

National Champion: Gerard Urimubenshi, PT 2 centres recruiting (Site Champions in each), 1st pt July 12, 2017 Recruitment as expected; intervention phase to begin

5 10 15 20 25 30 35 jul-17 aug-17 sep-17

  • kt-17

N Participants

Kigali 101 Butare 102 *3 patients refused *1 patient refused Approx. weekly recruitment rate 1/week 1/week 3/week 1/week 2/week 1/week 1/week 0.25/week

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Collaboration today..

Necessary for:

  • Detecting modest but worthwhile treatment effects
  • Accurate estimates of treatment effects across

different ethnicities and health care systems

  • Efficient knowledge translation

Progressive

  • Two way street

And it is an incredibly rewarding experience!