Data management groups often attempt to format the independent electronic data similar to the investigator data for ease of comparison. However, this traditional method often fails when confronting differences in the two review processes, particularly when there are multiple types of reviewers. For example, a radiologist is required to perform imaging measurements and an oncologist is required to review clinical data, with both reviewers working independently. This differs from the investigator who can fulfill both roles simultaneously. An enlarging pleural effusion, for instance, may instantly be diagnosed as benign by the investigator who has cytology results readily at hand. However, the independent radiologist may be forced to state "unknown" for a response, and defer the matter to the independent oncologist who has access to the clinical information.

The sponsor's data management group must be cognizant of differences like these and carefully consider the collection and analysis of independent reviewer data. More importantly, they must be a key player in the charter development process, when many of the decisions on data collection are made.

Sustainability issues

At the very least, the protocol may be a vehicle to highlight the existence of an independent imaging review and provide some high-level instruction to investigator sites.

Reviewer selection

While there is considerable desire by both the sponsor and the imaging core lab to limit the number of independent reviewers in an effort to control variability, reviewers often leave for unforeseen reasons during the review period. Likewise, study requirements may change, necessitating the addition of extra reviewers late in the review process.

It makes sense to assume that the ideal independent review process would utilize the skills of the most experienced thought leaders within the therapeutic area as independent reviewers. However, these experts often have very rigorous schedules and limited time to dedicate to independent review activities, which does not offer much flexibility with regard to timeline constraints. It is important during early charter discussions—dominated many times by scientific rather than operation concerns—to strike a balance between reviewer number and availability and the expected reviewer workload.

Conclusion

Prospectively defining the independent review process through documents such as the project plan, Independent Review Charter, and Investigator Site Manual—among other documents—allows the sponsor to manage the actual review process by managing the documentation.

The sponsor and imaging core lab must carefully consider the implications of these documents and set realistic expectations for how issues that arise can be easily mitigated. However, regardless of how well-defined the independent review process is, it often breaks down due to a lack of enforcement of the methods defined. Similarly, a process that is too stringent poses the risk of setting unrealistic expectations that the sponsor, investigator sites, and core lab simply cannot meet.

Poor communication as well as employee and reviewer turnover can also have detrimental effects on even the most well-planned processes. While situations may often not be anticipated, mitigation plans for what to do should issues arise can always be defined. The best defense in ensuring a successful review is to limit the occurrences that can be anticipated and prepare a solid plan for those that cannot be.

In the long run, prospectively defining how to handle common pitfalls in the independent imaging review process is far easier than trying to develop postreview contingency actions.

Stephen Bates is program director of the oncology/cardiology group in the medical imaging division of Perceptive Informatics, a PAREXEL company, 900 Chelmsford Street, Suite 309, Lowell, MA 01851. Kelie Williams, * BS, MS, MTPW, is a senior medical imaging technical writer in the imaging technical medical writing group at Perceptive Informatics, email: kelie.williams@perceptive.com

*To whom all correspondence should be addressed.

References

1. P. Therasse, S.G. Arbuck, E.A. Eisenhauer et al., "New Guidelines to Evaluate the Response to Treatment in Solid Tumors," Journal of National Cancer Institute, 92, 205–216 (2000).

2. World Health Organization, WHO Handbook for Reporting Results of Cancer Treatment, Offset Publication No. 48 (Geneva, Switzerland, 1979).

3. B.D. Cheson, J.M. Bennett, M. Grever et al., "National Cancer Institute-Sponsored Working Group Guidelines for Chronic Lymphocytic Leukemia: Revised Guidelines for Diagnosis and Treatment in Solid Tumors," Blood, 87, 4990–4997 (1996).