accreditation of research programs: how it might affect your research harvey murff, m.d., m.p.h....

Accreditation of Research Programs: Accreditation of Research Programs: How it Might Affect your ResearchHow it Might Affect your Research

Harvey Murff, M.D., M.P.H.Harvey Murff, M.D., M.P.H.

Director of Research Safety Director of Research Safety

GCRC, Vanderbilt University Medical GCRC, Vanderbilt University Medical CenterCenter


The problem that accreditation would The problem that accreditation would addressaddress

What is accreditationWhat is accreditation Why is it believed that accreditation might Why is it believed that accreditation might

helphelp Who will accreditation affectWho will accreditation affect

Human Subjects ProtectionHuman Subjects Protection-Background-Background

Nuremberg Code (1946-1949)Nuremberg Code (1946-1949) Declaration of Helsinki by World Medical Declaration of Helsinki by World Medical

Association (1963)Association (1963) National Research Act (1974)National Research Act (1974)

– Formed National Commission for the Protection of Formed National Commission for the Protection of Human Subjects of Biomedical and Behavioral Human Subjects of Biomedical and Behavioral Research (National Commission)Research (National Commission)

The Belmont Report The Belmont Report (1979)(1979)

Human Subjects ProtectionHuman Subjects Protection-Background-Background

National Commission described what would be National Commission described what would be the framework for IRB’sthe framework for IRB’s– Not adopted by all Federal AgenciesNot adopted by all Federal Agencies

The “Common Rule” published (1991) The “Common Rule” published (1991) Office of Inspector General (OIG) issues Office of Inspector General (OIG) issues

Intuitional Review Boards: A Time for Reform Intuitional Review Boards: A Time for Reform (1998)(1998)– IRB’s facing overwhelming demandsIRB’s facing overwhelming demands

Human Subjects ProtectionHuman Subjects Protection-Failures in the System-Failures in the System

OPRR halts research at Duke (May 1999)OPRR halts research at Duke (May 1999)– Several other sites temporarily shut downSeveral other sites temporarily shut down

– Noncompliant with human protection regulationsNoncompliant with human protection regulations

Death of Jesse Gelsinger (September 1999)Death of Jesse Gelsinger (September 1999)– Cited for no safety plan in proposalCited for no safety plan in proposal

OIG issues follow up to OIG issues follow up to A Time for ReformA Time for Reform– Again calls into question the effectiveness of IRB’sAgain calls into question the effectiveness of IRB’s

– Suggest greater attention to protecting human subject in Suggest greater attention to protecting human subject in any trial (not just gene therapy)any trial (not just gene therapy)

Human Subjects ProtectionHuman Subjects Protection-Regulatory Guidelines-Regulatory Guidelines

Secretary of Health and Human Services (2000)Secretary of Health and Human Services (2000)– commissions IOM to review human subjects protectioncommissions IOM to review human subjects protection

Two reports Two reports – ““Preserving Public Trust: Accreditation and Human Research Preserving Public Trust: Accreditation and Human Research

Participant Protection Programs” (2001)Participant Protection Programs” (2001)

– ““Responsible Research: A Systems Approach to Protecting Responsible Research: A Systems Approach to Protecting Research Participants” (2002)Research Participants” (2002)

Purpose of the IOM CommitteePurpose of the IOM Committee

1.1. Comprehensive assessment of research participant Comprehensive assessment of research participant protectionprotection

2.2. Review and consider proposed human research review Review and consider proposed human research review program performance standardsprogram performance standards

3.3. Recommend standards for accreditation of HRPPPs, Recommend standards for accreditation of HRPPPs, considering measures of structure, process, and considering measures of structure, process, and performance, as well as resource sufficiency performance, as well as resource sufficiency

4.4. Recommend steps that the organizations and institutions Recommend steps that the organizations and institutions than conduct research and that the federal government than conduct research and that the federal government should take to collect and analyze data to monitor and should take to collect and analyze data to monitor and evaluate how well the system for protecting human evaluate how well the system for protecting human subjects is operatingsubjects is operating

The Phases of Human ResearchThe Phases of Human Research

Research Question

Protocol Development

Scientific and Conflict of Interest Review

Ethical Review

Recruitment and Enrollment

Data Collection

Data Analysis/Study Close-Out

Dissemination

Individual Participant

Participant Perspective

Info

rmed

Con

sen

t

Saf

ety

Mon

itor

ing

Statement of ProblemStatement of Problem

Significant doubt exist regarding the capacity of Significant doubt exist regarding the capacity of the current system to meet its core objectivesthe current system to meet its core objectives

IRBs are “under strain” and “in need of reform”IRBs are “under strain” and “in need of reform” The existing regulatory framework cannot The existing regulatory framework cannot

adequate respond to the complex and ever-adequate respond to the complex and ever-changing research environment, with weaknesses changing research environment, with weaknesses related to gaps in authority, structure, and related to gaps in authority, structure, and resourcesresources

Human Research Participant Protection Human Research Participant Protection ProgramProgram

Performance Assessment

Monitoring and

Feedback

Education Quality Improvement

Participants

Research Organizations

IRBs Investigators

Research Involving Human Participants

Sponsors

Functions of a HRPPPFunctions of a HRPPP

Comprehensive review of protocolsComprehensive review of protocols– ScientificScientific

– Financial conflict of interestsFinancial conflict of interests

– Ethical reviewsEthical reviews

Ethically sound participant-investigator interactionEthically sound participant-investigator interaction Ongoing and risk-appropriate safety monitoringOngoing and risk-appropriate safety monitoring Quality improvement and compliance activitiesQuality improvement and compliance activities

– What are the types of quality problems?What are the types of quality problems?

Common Quality ProblemsCommon Quality Problems

Most common findings in quality assessment of Most common findings in quality assessment of clinical trialsclinical trials– Case report forms and study files incomplete, Case report forms and study files incomplete,

inaccurate, and not appropriate for safety trackinginaccurate, and not appropriate for safety tracking

– Failure to distinguish research from standard of careFailure to distinguish research from standard of care

– Failure to submit or amend IND/IDE to FDAFailure to submit or amend IND/IDE to FDA

– Poorly written protocols and data collection toolsPoorly written protocols and data collection tools

– Informed consent form inadequacies/inconsistenciesInformed consent form inadequacies/inconsistencies

– No study coordinator with defined authorityNo study coordinator with defined authority

– Post-approval monitoring for data integrity inadequatePost-approval monitoring for data integrity inadequateSource- Sherwin, Research Practitioner, 2002

What is Accreditation?What is Accreditation?

A process based on self- and peer assessment for public accountability A process based on self- and peer assessment for public accountability and improvement of performance quality. Peers assess the quality of and improvement of performance quality. Peers assess the quality of an institution or academic program and assist the faculty and staff in an institution or academic program and assist the faculty and staff in improvement. improvement. – self-study using the accrediting organization’s set of expectations about self-study using the accrediting organization’s set of expectations about

quality (standards, criteria) as their guide. “quality (standards, criteria) as their guide. “– A team of peers, selected by the accrediting organization, reviews the A team of peers, selected by the accrediting organization, reviews the

evidence, visits the campus to interview the faculty and staff, and writes a evidence, visits the campus to interview the faculty and staff, and writes a report of its assessment including recommendation to the commission of report of its assessment including recommendation to the commission of the accrediting organization (group of peer faculty and staff, the accrediting organization (group of peer faculty and staff, professionals, and public members). professionals, and public members).

Grounded by a set of expectations about quality and integrity, the Grounded by a set of expectations about quality and integrity, the commission reviews the evidence and recommendation, makes a commission reviews the evidence and recommendation, makes a judgment, and communicates the decision to the institution and other judgment, and communicates the decision to the institution and other

constituencies if appropriate.constituencies if appropriate.

Why AccreditationWhy Accreditation

Accreditation versus regulationAccreditation versus regulation– BenefitsBenefits

» Reduces cost of government oversightReduces cost of government oversight

» More flexible and responsive to change that federal More flexible and responsive to change that federal agenciesagencies

» More responsive to the “regulated”More responsive to the “regulated”

– DisadvantagesDisadvantages» Less accountable Less accountable

““fox is guarding the henhouse”fox is guarding the henhouse”

Proposed Accreditation AgenciesProposed Accreditation Agencies

– National Committee on Quality Assurance National Committee on Quality Assurance (NCQA)(NCQA)

» Contracted by the VAContracted by the VA

» Undergoing pilot testingUndergoing pilot testing

» Centers poorly preparedCenters poorly prepared

– Association for the Accreditation of Human Association for the Accreditation of Human Research Protection Programs, Inc (AAHRPP)Research Protection Programs, Inc (AAHRPP)

» Few institutions already on boardFew institutions already on board

Who is advocating accreditation?Who is advocating accreditation?

– Institute of MedicineInstitute of Medicine– Department of Veterans AffairsDepartment of Veterans Affairs– National Bioethics Advisory CommissionNational Bioethics Advisory Commission– Inspector General of the Department of Health Inspector General of the Department of Health

and Human Servicesand Human Services– American Association of Medical CollegesAmerican Association of Medical Colleges– Members of CongressMembers of Congress– Office of Human Research Protection (OHRP)Office of Human Research Protection (OHRP)

How accreditation should improve How accreditation should improve quality and safetyquality and safety

Grounded in continuous quality Grounded in continuous quality improvement theoriesimprovement theories

Requires measuring of processes and Requires measuring of processes and outcomes, introducing changes, and re-outcomes, introducing changes, and re-measuringmeasuring– Statistical process controlStatistical process control

““If you always do what you If you always do what you always did, you will always get always did, you will always get

what you always got”what you always got”

Definitions:Definitions:

QualityQuality– IOM definition: IOM definition:

» ““degree to which health services for individuals and degree to which health services for individuals and populations increase the likelihood of desired health outcomes populations increase the likelihood of desired health outcomes and are consistent with current professional knowledge”and are consistent with current professional knowledge”

Quality AssuranceQuality Assurance» ““The policy, procedures, and systematic actions established in The policy, procedures, and systematic actions established in

an enterprise for the purpose of providing and maintaining a an enterprise for the purpose of providing and maintaining a specified degree of confidence in data integrity and accuracy specified degree of confidence in data integrity and accuracy throughout the lifecycle of the data, which includes input, throughout the lifecycle of the data, which includes input, update, manipulation, and output.”update, manipulation, and output.”

Model of Continuous Quality ImprovementModel of Continuous Quality Improvement

PlanAct

Study Do

Barriers to a Quality Assurance ApproachBarriers to a Quality Assurance Approach

What’s the evidence?What’s the evidence? What outcomes?What outcomes? What methods?What methods? What resources?What resources? Local buy-inLocal buy-in

Who will be evaluated in accreditation Who will be evaluated in accreditation programs?programs?

InstitutionsInstitutions

Institutional Review BoardsInstitutional Review Boards

InvestigatorsInvestigators

InvestigatorsInvestigators

VA’s GCP ChecklistVA’s GCP Checklist– Paperwork to be completed Paperwork to be completed

documenting compliance documenting compliance with protocolwith protocol

Investigator performance Investigator performance measuresmeasures– Using only trained Using only trained

individuals to gather individuals to gather consentconsent

– Documentation of consentDocumentation of consent

– AE reportingAE reporting

Investigator Investigator Responsibilities for Responsibilities for Reporting to IRBReporting to IRB– Reporting of unanticipated Reporting of unanticipated

problemsproblems– Submission of protocol Submission of protocol

changeschanges– Reporting of protocol Reporting of protocol

deviationsdeviations Obtaining informed consentObtaining informed consent

– When and whereWhen and where– Opportunity to consider to Opportunity to consider to

participateparticipate– ComprehensionComprehension

General Recommendations of IOMGeneral Recommendations of IOM

1.1. Protect Every Research ParticipantProtect Every Research Participant2.2. Refocus the mission of the IRB on the Refocus the mission of the IRB on the

thorough ethical review and oversight of thorough ethical review and oversight of research protocolsresearch protocols

3.3. Recognize research participants’ Recognize research participants’ contribution and integrate them into the contribution and integrate them into the systemsystem

4.4. Maintain high standards for the continuing Maintain high standards for the continuing review of HRPPP performancereview of HRPPP performance

Protect Every Research ParticipantProtect Every Research Participant

Establish accountability within an ethical Establish accountability within an ethical research cultureresearch culture– Accountability Accountability – Adequate resourcesAdequate resources– Ethics education programsEthics education programs– TransparencyTransparency

Provide sufficient fundsProvide sufficient funds

Refocus IRB mission on ethical review of Refocus IRB mission on ethical review of protocolsprotocols

Distinguish scientific, conflict of interest, Distinguish scientific, conflict of interest, and ethics review mechanismsand ethics review mechanisms

Emphasize risk-appropriate protectionEmphasize risk-appropriate protection Increase program productivityIncrease program productivity

Recognize and Integrate Participant Recognize and Integrate Participant ContributionsContributions

Revitalize informed consentRevitalize informed consent Increase system accessibilityIncrease system accessibility Compensate participants for research-Compensate participants for research-

related injuryrelated injury

Maintain VigilanceMaintain Vigilance

Collect national level data about the systemCollect national level data about the system Enhance safety monitoringEnhance safety monitoring Continuously improve qualityContinuously improve quality Manage potential conflicts of interestManage potential conflicts of interest Periodically assess the national systemPeriodically assess the national system

accreditation of research programs: how it might affect your research harvey murff, m.d., m.p.h....

Documents

accreditation of hrppps

responsible research

research participants

national research act

human services

research harvey murff

system oprr halts research

irbs national commission