Medical imaging is a technique used in the field of medicine to create visual representations of the interior of a body for clinical analysis and medical intervention. Medical imaging has a critical impact on the advancement of medical science in several key ways:
- Imaging biomarkers aid in the evaluation of efficacy quickly, helping to avoid further investment in ineffective therapies
- By helping sponsors identify the patients most likely to benefit from new therapies
- Enabling researchers to meet endpoints and other eligibility criteria
- Various imaging techniques—such as CT, MRI, and PET scans—serve to provide real-time visibility that improves study efficiency
Today, medical imaging data is crucial in the research and development of novel products. The centralization of medical images ensures standardized acquisition parameters as well as quality control, and in the case of image analysis, reduces variability in read results. This blog explores the pivotal role of centralized medical imaging across the entire spectrum of clinical trials, spanning from early-phase investigations to post-Phase IV trials.
Phase I Clinical Trials
Phase I clinical trials present the first opportunity to clinically evaluate a drug candidate. Here, research teams aim to evaluate the drug across a range of doses for safety and dose escalation purposes. During Phase I, medical images are typically collected for publications, for translational medicine, or for internal use amongst the research team. Since Phase I studies also enable evaluation of the effect of the drug on diseases, imaging provides information to help with early-stage decisions and towards improving patient outcomes in the long run. As an example, in oncology Phase I trials where subjects have refractory advanced solid tumors, imaging is applied to acquire evidence of anti-tumor activity via lesion shrinkage on CT scans, which may indicate successful drug action.
For these early-phase trials, a centralized review of medical imaging on a cloud-based platform can be useful since it provides more timely, standardized, and accurate results for research teams as they plan for the Phase II trials. In early-phase studies where changing scopes are common, having a flexible centralized medical imaging solution able to account for changing scopes is extremely valuable.
Phase II Clinical Trials
After a safety profile has been established, along with the drug dose and scheduling, Phase II clinical trials begin. At this stage, the clinical trial’s purpose is to evaluate drug efficacy and safety within a target patient population. Conducted across multiple clinical centers, the goal of Phase II trials is to obtain sufficiently robust data, pursue the clinical trial with a broader patient population, and enable key decisions regarding investment in further programs. In Phase II oncology studies, for example, clinical imaging can be assessed with standard response criteria such as RECIST (Response Evaluation Criteria in Solid Tumors). These responses are classified as complete response, stable disease, partial response, or disease progression—depending on the percentage of reduction in tumor size.
Phase III Clinical Trials
Phase III clinical trials provide evidence for the safety and efficacy of a drug within a large population for which drug administration is indicated. These studies typically involve many patients and investigator sites spread across the globe, with many medical images to be collected and analyzed. The results from Phase III trials are submitted to regulatory agencies, such as the FDA or the EMA, with the aim of achieving market approval for a given drug. These studies tend to be designed as double-blind with parallel arms comparing the new treatment with the standard therapy. For a typical Phase III solid tumor study, lesion size measurements taken from the RECIST evaluation use CT for around 90% of evaluations, with the remainder provided by MRI. However, there are many other modalities of imaging utilized for Phase III clinical trials, such as PET scanning, X-rays, ultrasound, and nuclear medicine imaging. The specific choice of imaging modality and protocol should be carefully defined in the trial's protocol and is crucial for obtaining reliable data for primary and secondary endpoints.
For Phase III trials and even some large Phase II trials, an independent central review (ICR) is required by FDA recommendation when results of image measurements are essential for the assessment of efficacy endpoints. By using a 2+1 read design, the chosen radiologists are independent and blinded to the given treatment as well as to any clinical information regarding the patient—meaning that design errors, potential bias, and variability in read results are kept at bay.
Phase IV Clinical Trials
Following approval by the FDA, and manufacturing of the drug on a large scale by the sponsor, the development process enters Phase IV of clinical trials. In Phase IV clinical trials, medical imaging can continue to play a role in assessing the safety, efficacy, and potential side effects of a drug or treatment that has already been approved and is in the market. For example, imaging techniques such as MRIs, CT scans, X-rays, and others help to monitor patients for any potential long-term adverse effects or unexpected complications reported by users related to the treatment.
Conclusion
Phase I and II studies in clinical trials provide complementary biomarkers that, alongside non-imaging endpoints, strengthen confidence in evaluating the therapeutic efficacy of a drug. In Phase III studies, centralized imaging can be instrumental in securing regulatory approval for the new drug. Centralizing your medical imaging data in one secure location allows the sponsor to benefit from a consistent application of response criteria or specialized image analysis.
Each project has its own sets of unique challenges and requirements and the need to standardize and centralize your medical imaging data can prove daunting. That’s why sponsors often use the services of a specialized medical imaging CRO. The imaging CRO is a crucial asset in the development of clinical trials, offering expertise in medical imaging, experience across clinical trial phases and a variety of therapeutic areas, and a robust and flexible technology infrastructure.
Whether you’re conducting an early-stage project or a multicenter international trial, different options for image collection and interpretation are available. These typically range from a “collect and hold” (C&H) option up to a full service package with independent centralized review.
- Collect & Hold for early-phase clinical trials which can utilize local image review. Here, image data is collected and centrally archived without quality control.
- Collect & Hold service with or without quality control processes.
- Collect & Hold including quality control activities accompanied by an optional read. This could be a single read design or a 2+1 read design.
- Full service centralized medical imaging offerings enable real-time reads when needed.
Keosys’s Read System is a proprietary web-based technology with an integrated read system. It’s designed specifically for clinical trials to limit reader subjectivity, increase measurement and quantification accuracy, and improve all-around operational efficiency, data quality, and traceability. Our technology has been validated with all major vendors and supports imaging modalities such as CT, MRI, PET, PET/CT, SPECT, SPECT/CT, conventional radiology, and more.
Our in-house platform enables us to offer tailored solutions that align with your specific needs. At Keosys, we prioritize customization and client satisfaction, and are committed to providing you with the best options.
Contact us today to learn more and discuss our services.
