Smo Vs Cro

Why a SMO is not a CRO, or is it? Stan W. Woollen Associate Director for Bioresearch Monitoring Office for Good Clinical Practice, Office of the Commissioner FDA Oct. 2001

A regulator’s perspective on CROs/SMOs • Today’s Clinical Trial Environment – Environmental pressures driving evolutionary changes – Identifying the different species and their place in the new environment

• CRO vs. SMO - A new species – Similarities and differences – Regulatory issues

Today’s Clinical Trial Environment Pressures for change • Increased competition for subjects and investigators – Large trials widely dispersed geographically over many sites – Influx of new Clinical investigators – Principal investigators remote to sites • Increased need for speed – Remote data collection and electronic transmission – Central IRBs and study monitoring • Increased reliance on contractors (e.g. CROs/SMOs) – greater fragmentation in dispersing study functions

Today’s Clinical Trial Environment Identifying the species • Players identified by regulation: – Investigator/Subinvestigator – Sponsor – Sponsor-investigator – Subject

– Contract Research Organization (CRO) – Applicant

– Institutional Review Board (IRB) – Institution

Today’s Clinical Trial Environment Identifying the species • Players defined ad hoc – Site Management Organization (SMO) – – – – –

Monitors/Clinical Research Associate Study Nurse/Coordinator Data manager Medical monitor QA auditor

• Anyone who participates in a study activity

Today’s Clinical Trial Environment Assigning Responsibilities • Responsibilities assigned by regulation – 21 CFR 312 Subpart D- Responsibilities of Sponsors and Investigators – 21 CFR 56 Standards for composition, operation, and responsibility of an IRB – 21 CFR 50 Responsibility for obtaining informed consent • Sponsors, Investigators and IRBs by regulation

Today’s Clinical Trial Environment Assigning Responsibility • Responsibilities assigned by contract – 312.52 Transfer of obligations to a CRO • Any or all sponsor obligations may be transferred • Transfer must be described in writing • If not all obligations are transferred each obligation being assumed by the CRO must be described • If all are transferred a general statement is acceptable • Any obligation not covered shall be deemed not to have been transferred

Today’s Clinical Trial Environment Assigning Responsibility • Responsibilities assigned by contract – 312.52 Transfer of obligations to a CRO, legal liability • A CRO that assumes any obligation of a sponsor shall comply with the specific regulations applicable to the obligation • A CRO is subject to the same regulatory action as a sponsor for failure to comply • All reference to “sponsor” in the regs. apply to a CRO to the extent that it assumes one or more obligations of the sponsor

What is a Contract R

esearch

Organization?

• A CRO means a person that assumes, as an independent contractor with the sponsor, one or more of the obligations of a sponsor, e.g.., design of a protocol, selection or monitoring of investigations, evaluation of reports, and preparation of materials to be submitted to the FDA. • To the extent that an SMO meets this definition it would be considered a CRO

Determining Responsibility by Function • IF YOU HAVE CONTRACTED WITH THE SPONSOR TO DO ANY OF THE FOLLOWING…. – Select Qualified Investigators.* – Provide investigators with information they need to conduct an investigation properly. – Ensure proper monitoring of the investigation(s) – Ensure study is conducted in accordance with study plan and protocol – Control investigational product(s) – Safety reporting • YOU MAY BE LEGALLY LIABLE AS A SPONSOR

What is a Site Management Organization? (The world according to Stan)

• A SMO means a person that assumes, as an independent contractor with the clinical investigator, one or more of the regulatory obligations of a clinical investigator, e.g., preparation and maintenance of case histories, ensuring compliance with IRB review and informed consent requirements, AE reporting etc.

Determining Responsibility by Function • IF YOU Sign a FDA Form 1572…… YOU ARE AN INVESTIGATOR FULLY COMMITTED TO: – Personally conduct or supervise the investigation – Ensure that all associates, colleagues, and employees assisting in study conduct are informed about their obligations – Conduct the study in accordance with the protocol – Comply with all requirements regarding obligations of clinical investigators (including preparation and maintenance of records) – Inform subjects drugs are being used for investigational purposes and ensure informed consent and IRB requirements are met – Report Adverse Events to the sponsor – Read and understand the investigator’s brochure

CRO vs. SMO Similarities and differences • Both are contractors the principal differences are with whom they contract, services contracted for, and their legal liability – CROs contract with sponsors and are explicitly regulated – CROs are legally liable for the obligations they assume – SMOs contract with clinical investigators and are not explicitly regulated – SMOs are not legally liable for the CI obligations they assume

Regulatory Issues • SMOs assume clinical investigator duties but the regulations make no provisions for transfer of CI responsibilities. CI remains responsible, though they may not know it. • CROs subcontract sponsor obligations to SMOs

Regulatory Issues • A CRO’s complaint – Forced to use SMO network for whom compliance cannot be assured • one principal investigator at SMO HQ with hundreds of subinvestigators geographically dispersed • physical access to site denied to CROs/Sponsor monitors • all monitoring to be done at central site only copies available for audit • IRB selected by SMO remote to CI, unknown to CRO

Know Your Responsibilities

It’s better to have them written in a contract rather than in a letter from the FDA