Thursday, June 07, 2007

Managing risk in clinical outsourcing


Sponsors need to ensure they are managing the risk involved in clinical outsourcing, particularly when dealing with multiple contractors.

Leading contract research organisations (CROs) managed nearly 23,000 Phase I-IV studies from 152,000 clinical sites worldwide in 2004, the most recent year for which data are available, according to the Tufts Center for the Study of Drug Development.

This reliance on CROs has only increased since then, both in clinical and pipeline drug development, and manufacturers need to make sure they remain vigilant and involved in any outsourced R&D because ultimately, the responsibility for the ongoing safety evaluation of the investigational products and for reporting any information that could adversely affect the safety of trial subjects, lies on the sponsor's shoulders, stated the report, citing section 5.2 of the International Conference on Harmonisation's (ICH) Guideline for Good Clinical Practice.

Monitoring CRO performance and compliance is crucial to mitigating the potential risks that manufacturers face in any third-party collaboration, from R&D to manufacturing, distribution, and advertising. For CROs, this includes reviewing patient records and medical charts.

The more complex the outsourced task, the greater the risk and this potential for risk may also increase when clinical protocols are developed by several physician-investigators and involve multiple investigational sites and other third parties. As a general rule, "as more people and systems are involved, additional prudence may be needed", the report indicated.

To try and put the extent of these clinical outsourcing relationships into perspective, the report contained a graph giving a snapshot of the ten big pharmaceutical companies who are engaging in this activity. Pfizer was associated with the most relationships, with 340, while Novartis and Merck followed closely behind with 318 and 317 respectively. Trailing the top ten list were Sanofi-Aventis on 119 and Amgen on 115.

"This data is meant to be indicative of the scale that outsourcing is now being done by pharmaceutical companies and raises the question of how the firms that are or have been involved with so many third party companies are making sure they are managing the risk that comes with having so many of these relationships," Andrew Jones, Pharmaceutical analyst from Ernst & Young told

Meanwhile, the authors also pointed out that in addition to monitoring ongoing third party activities, sponsors also need to establish a "strong foundation for CRO compliance and integrity", citing again, the ICH guideline, which states that any trial-related duty that is transferred from sponsor to CRO should be specified in writing.

The importance of this is highlighted by the high-profile Phase I drug trial disaster last year in which six volunteer subjects ended up in intensive care, where Parexel was hired to conduct the trial by German developer of the drug TeGenero.