# Presentation: 090137

## 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 Research 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 **