For Clinical Trials, Centralized Imaging Data Collection and Review Is a Must
By Joseph Pierro, chief medical officer of Biomedical Systems.
In many clinical trials, clinical imaging plays an important role in the drug development process. Whether the trial involves drugs, biologics, or devices, imaging may be used to measure the efficacy and safety of the investigational product. An independent assessment based on the centralized collection of imaging data is often considered an essential element for almost all regulatory approvals.
Several existing guidance documents describe the appropriate selection of imaging-related endpoints, as well as the independent, centralized review process. It’s important to understand these requirements in the creation of the development plans and study protocols. Over the years, pharmaceutical companies have shown some reluctance to adopting full-scale centralized data policies.
This situation is beginning to change, and the value of standardized methods and interpretations are increasingly accepted as best practices in the implementation of multicenter, international studies. Cloud technology is poised to launch a “clinical trial revolution,” but this golden age of centralization is yet to fully extend to imaging data. To reap the full rewards of technological progress, imaging contract research organizations and pharma companies can go further with data collection and integration.
Centralized imaging can provide a solid foundation for standardizing protocol-required imaging techniques. It facilitates the oversight and certification of site competence. It also allows researchers to monitor protocol compliance and performance during trials, correcting issues in real time, rather than after the data has been analyzed where possible.
When selecting a clinical research site, oversight of data that has been collected and centralized helps assess the personnel who will be performing tests. Oversight also verifies that the site, staff, and equipment all meet protocol needs. During an independent centralized review, the core lab can control information provided to expert readers, meaning that a standard clinical package or display can be provided to all independent assessors, minimizing external influences and bias.
Most importantly, perhaps, is that centralized imaging data helps monitor performance over the duration of a study, improving overall image collection quality and resulting in more consistent (and higher) data. With better data comes better interpretations, and fewer exams will fail to meet protocol standards during independent reviews. The independent image collection and review process is carefully explained in the imaging site manuals, imaging review charters — including details on assessments or endpoint response criteria — and other documents recommended by regulatory agencies.
Small, early-phase clinical trials may not fully benefit from the advantages of data centralization, but they could still gain value from centralized image collection and review. Having access to all of the study images allows the sponsor to perform additional exploratory analyses on the data set. For example, sponsors can study the different levels of treatment response or combinations of response as they begin to understand clinical benefits of their investigational products. The decision about when to perform centralized image review and collection depends on the therapeutic area and is a matter of risk-benefit for the sponsor. Many people look at the central review as insurance policies for their development programs asset.
It is also important to note that central review and collection can reduce quality and reviewer variability. Additionally, centralized data review has been shown to maintain the same level of statistical power while decreasing the overall sample size.
Of course, clinical imaging interpretations differ from regulatory readings required for clinical research approval. However, with global trial regulations evolving — and guidelines from the World Health Organization, the International Committee of Medical Journal Editors, and the Declaration of Helsinki all in force — centralized monitoring is increasingly invaluable. Plus, noncompliance can be costly.
Moving forward, pharma companies need to gain a better understanding of regulatory requirements for approval and submission of endpoints, whether radiologic, surrogate, or biomarker. They must also recognize the role that imaging will have in this process. This role may change as a program progresses from early- to late-phase development, but imaging will continue to be important at all stages, from early tests on drug bio-distribution and receptor binding in targeted organs to later-phase study assessments focused on imaging outcomes.
Centralizing data will only make these assessments easier. It will help all involved to understand the impact of quality on data variability, as well as the impact on the sponsors’ abilities to determine and understand post-treatment changes, trends, or signals. This means consulting experts early in the development process to guide and assist in the protocol design and the collection of data. Each company must define its own standards, and while helpful advice is available online, it is no substitute for the mind of a knowledgeable expert who understands the potential costs and benefits to a company.
As medical science breaks new ground in the treatment of disease, technologies are making the lives of clinicians and assessors easier. It would be foolish for us to ignore these developments.
Joseph Pierro is chief medical officer of Biomedical Systems, a premier global provider of centralized diagnostic services. He has served in global senior level positions within the pharmaceutical industry and as a medical reviewer at the FDA Center for Drug Evaluation and Research. His thorough understanding of regulatory submission requirements and outstanding track record of success with regulatory approvals and responses to regulatory authorities make him an asset to Biomedical Systems’ Scientific Affairs team.