Challenges in classifying adverse events in cancer clinical trials
Download
1 / 26

Challenges in Classifying Adverse Events in Cancer Clinical Trials - PowerPoint PPT Presentation


  • 88 Views
  • Uploaded on

Challenges in Classifying Adverse Events in Cancer Clinical Trials. Steven Joffe, MD, MPH Dave Harrington, PhD David Studdert, JD, PhD Saul Weingart, MD, PhD Damiana Maloof, RN . Disclosure. Member of clinical trial adverse event review board for Genzyme Corp (not oncology-related).

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' Challenges in Classifying Adverse Events in Cancer Clinical Trials' - jules


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.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
Challenges in classifying adverse events in cancer clinical trials

Challenges in Classifying Adverse Events in Cancer Clinical Trials

Steven Joffe, MD, MPH

Dave Harrington, PhD

David Studdert, JD, PhD

Saul Weingart, MD, PhD

Damiana Maloof, RN


Disclosure
Disclosure Trials

  • Member of clinical trial adverse event review board for Genzyme Corp (not oncology-related)


Adverse events in clinical trials
Adverse Events in TrialsClinical Trials

  • Adverse events (AEs) are critically important outcomes of clinical trials

    • Human subjects protection

    • Endpoints for judgments about benefits & risks of study interventions

  • Captured on Case Report Forms

  • Reported to oversight agencies


Components of ae assessment
Components of Trials AE Assessment

  • Type

  • Severity

  • Relatedness to study agent(s)

  • Expectedness


Components of ae assessment1

Global judgment about reportability to IRB Trials

Components of AE Assessment

  • Type

  • Severity

  • Relatedness to study agent(s)

  • Expectedness


Reporting criteria to dana farber irb
Reporting Criteria Trials(to Dana-Farber IRB)

  • Grade 5 (fatal)

  • Grade 4, unless specifically exempted

  • Grade 2/3, if unexpected AND possibly, probably or definitely related

  • Virtually identical to NCI’s Adverse Event Expedited Reporting System (AdEERS) criteria


Ae grading in oncology
AE Grading in Oncology Trials

  • NCI’s Common Terminology Criteria for Adverse Events (CTCAE) typically used

    • Effort to standardize nomenclature

    • developed by consensus methods; no formal process to establish reliability of grading

http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_v30


Aims Trials

  • To assess the validity of physician reviewers’ determinations about whether AEs in cancer trials meet IRB reporting criteria

  • To assess the interrater reliability of reviewers’ determinations about whether AEs that occur in cancer trials meet IRB reporting criteria

  • To assess the validity and reliability of revie-wers’ judgments about the components of AEs



Panelists roles
Panelists’ Roles Trials

  • Review primary data from criterion sets of AEs

  • Rate each AE:

    • Classification

    • Grade

    • Relatedness

    • Expectedness

    • Reportable to IRB

}

from CTCAE





Statistical analysis
Statistical Analysis Trials

  • Validity of judgments regarding reportability to IRB

    • % agreement with gold standard

  • Interrater reliability of raters’ judgments

    • Kappa coefficients


Results

Results Trials






Role of experience service as pi
Role of Experience: TrialsService as PI

Kappa


Role of experience number of ae reports filed
Role of Experience: TrialsNumber of AE Reports Filed

Kappa


Conclusions
Conclusions Trials

  • Oncologists’ judgments about whether or not AEs require reporting to the IRB show high agreement with gold standard

  • Interrater reliability of oncologists’ judgments about components of AEs varies

    • High: expectedness of AE; need for reporting

    • Moderate: grade of AE

    • Low: relationship of AE to study agents


Limitations
Limitations Trials

  • Small sample sizes

    • Criterion set of AEs

    • Panel of physician reviewers

  • Generalizability of set of AEs

  • Reviewers may not reflect population of investigators who file AE reports

  • Judgments based on document review rather than on firsthand knowledge


Thoughts about direction of bias in agreement statistics
Thoughts About Direction of Bias in Agreement Statistics Trials

  • Factors biasing towards less agreement

    • Reviewer experience

  • Factors biasing towards greater agreement

    • Standardized set of documents for review

    • Criterion set selected based on maximum agreement among expert panel reviewers


Implications
Implications Trials

  • Judgments about AEs are complex

    • Human subjects: efforts to enhance reliability, or to minimize reliance on judgments about causation, are needed

    • Science: toxicity data from uncontrolled trials may be misleading

    • RCR: education about need for reporting is important but insufficient


Acknowledgments

Debra Morley Trials

Anna Mattson-DiCecca

Physician panelists

ORI

NCI

Milton Fund

Acknowledgments


ad