1 / 21

James Gordon Department of Biokinesiology & Physical Therapy University of Southern California

A Framework for Staging Clinical Trials Pre-Clinical to Phase IV in Rehabilitation. James Gordon Department of Biokinesiology & Physical Therapy University of Southern California. Purpose…. Review standard framework for “staging” clinical trials

guido
Download Presentation

James Gordon Department of Biokinesiology & Physical Therapy University of Southern California

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. A Framework for Staging Clinical Trials Pre-Clinical to Phase IV in Rehabilitation James Gordon Department of Biokinesiology & Physical Therapy University of Southern California

  2. Purpose… • Review standard framework for “staging” clinical trials • Developing a novel treatment technique from its discovery to a fully tested, established intervention • Naïve view: that this will happen automatically • Mature view: we need to plan this “staging” in advance

  3. Caution… • The language and methodology of clinical trials was developed in the context of developing new drugs. • Rehabilitation is not a drug • Rehabilitation has unique characteristics • We should adapt this framework and not be afraid to deviate from tradition

  4. Clinical Trials in Rehabilitation • Fitzgerald, G.K., Delitto, A. (2001) Considerations for planning and conducting clinic-based research in physical therapy. Phys Ther 81:1446 –1454. • Barbeau, H., Fung, J. (2001) The role of rehabilitation in the recovery of walking in the neurological population. Curr Opin Neurol 14:735-740.

  5. What is clinical research? • Research that takes place in clinical settings • Case studies • Case series • Descriptive & retrospective studies • Clinical trials • Randomized controlled trials

  6. What is a clinical trial? • A research study in which a specific treatment is compared to a control condition • Control Condition • No treatment • Pre-treatment (pre- vs. post-) • Placebo • Standard care • Another experimental intervention

  7. What is a randomized controlled trial? • A type of clinical trial in which the subjects are allocated at random to receive one of several different clinical interventions • Randomization reduces the potential for bias • RCT – the gold standard

  8. Clinical Trial – alternate definition • A clinical trial is a research study that you conduct when you already know what the result will be

  9. Staging Clinical Trials • Efficacy vs. Effectiveness • Stages of Development • Discovery & pre-clinical studies • Phase I, II, III, IV

  10. Efficacy and effectiveness • Efficacy – Does the intervention work in tightly controlled conditions? • Strict inclusion/exclusion criteria • Highly standardized treatments • Explicit procedures for ensuring compliance • Focus on direct outcomes

  11. Efficacy and effectiveness • Effectiveness – Does the intervention work in ‘real world’ conditions? • Looser inclusion/exclusion criteria • Treatments carried out by typical clinical personnel • Little or no provision for insuring compliance • Focus on less direct outcomes (e.g., quality of life)

  12. Efficacy and effectiveness studies optimize different aspects of validity… clinical research [intervention] studies continuum: InternalValidity ExternalValidity Efficacy Effectiveness Experimental (RCTs) Quasi-experimental/ Observational designs Most studies fall somewhere in between these anchors From: Winstein & Lewthwaite, Eugene Michels Forum: CSM, Nashville TN, February 7, 2004

  13. Stages in the Development of BWSTT From Barbeau & Fung (2001) Curr Opin Neurol 14:735-740.

  14. Stages of Development of New Drug or Intervention • Basic & Translational Science • Discovery • Preclinical • Clinical Trials • Phase I • Phase II • Phase III • Phase IV

  15. Basic & Translational Science • Discovery • A new therapeutic effect is reported • Often in animal studies • Also, human studies in “normal” subjects • Preclinical • Safety is demonstrated in animal studies • Potential therapeutic efficacy observed in human subjects

  16. Clinical Trials • Phase I • Demonstration of safety & feasibility in patients • Small n • Often not true RCT’s • Include case studies and case series • Phase II • Focus on efficacy in ‘small’ groups • Ideally, these are RCT’s • Not necessarily randomized, e.g., if outcomes can be measured objectively • Dose-response studies

  17. Clinical Trials… • Phase III • Designed to assess effectiveness • Compare drug/intervention with standard treatment • Usually large-scale RCTs • Phase IV • Studies that monitor adverse effects after approval • Surveillance studies and surveys • Not RCTs

  18. Clinical Trial Phases An overlapping continuum Safety Feasibility Efficacy Effectiveness Safety I II III IV

  19. Should we worry about phases? • Strict adherence to the definitions of phases is not important • What is important is to plan the process of moving from safety and feasibility to efficacy to effectiveness

  20. Rehabilitation has unique characteristics • Patient is an active participant • Compliance is not enough… • Blinding is difficult • Placebos are difficult to construct • The proper level of analysis is difficult to establish • What unit should be studied? • Avoid comparisons of interventions at different levels • Outcomes are difficult to measure • Especially at disability level • Effects take a long time to emerge • Long-term follow-up is essential

  21. Thank you… For ‘handouts’, contact me: jamesgor@usc.edu

More Related