HealthcareWhy Clinical Trial Imaging Needs A Seat At The Protocol Design Table

Early imaging integration and planning avoid trial delays, protocol amendments, and concerns over data quality.

Introduction

Imaging is central to many modern-day clinical trials, especially in therapeutic areas such as oncology, neurology, and obesity/weight loss. Proactive and therapeutically aligned decisions about imaging processes are a benchmark of clinical trial success, providing the data needed to evaluate treatment response and the cohesion and clarity needed for regulatory acceptance. Both of these aspects are required to bring much-needed treatments into clinical practice.

The FDA’s Clinical Trial Endpoint Process Standards Guidance implies that clinical trial imaging considerations should be integrated into protocol design early, ideally during the initial trial planning stage. However, all too often, centralized imaging is considered at a later stage, leading to protocol misalignment, inconsistent data, and delayed clinical trial timelines. This article will evaluate the current landscape of clinical trial imaging, including an overview of regulatory guidance, to highlight why clinical trial imaging needs a seat at the protocol design table.

Regulatory guidance on clinical trial imaging

Many regulatory authorities emphasize the importance of early and structured integration of clinical trial imaging protocols within clinical trial design. Imaging can provide compelling biomarkers and surrogate endpoints within a trial which can accelerate the drug development process, but to ensure the reliability and integrity of this imaging data, guidance must be followed. Regulatory bodies, including the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA)  supply detailed guidance on the proper planning and execution of clinical trial imaging.

FDA guidance focuses on image acquisition, display, archiving, and interpretation process standards, and encourages the development of clinical trial imaging methodology, including modality-specific technical details, image interpretation, and image archiving procedures to be determined before imaging commences. Modality-specific parameters and standardized imaging methodologies must be predefined, according to such standards, and applied consistently across all clinical trial sites.

EMA guidance on risk-mitigation strategies encourages the development of integrated protocols, where imaging, safety, and efficacy endpoints are designed and aligned together from the beginning to mitigate risk and uncertainty, particularly in the context of human trials. This guidance emphasizes the strategic alignment of imaging within the entire clinical trial ecosystem, highlighting imaging-derived data as being integral, requiring appropriate planning, clinical justification, and operational feasibility in relation to the overall study design and aims. Imaging guidelines endorse early consideration of quality assurance and control procedures, blinding and central review strategies, and appropriate data transfer and storage protocols, all of which support the overall study outcome and the integrity of the data.

The current landscape of imaging integration

Clinical trial imaging adds immense value to clinical drug development programs, providing objective, quantifiable, and often non-invasive assessment data on disease progression, safety and toxicity profiles, and therapeutic response. However, in the face of increasingly complex clinical trial design, modality-specific techniques, and analytical variability, imaging strategy is becoming a challenge.

According to a review published in Nature Reviews Clinical Oncology, each imaging modality comes with unique costs, data handling requirements, and interpretation considerations, highlighting the importance of early imaging planning in light of increasingly complex imaging modalities. Studies need to pre-determine purpose-built protocols with clear links to clinical outcome and value, and in the case of imaging biomarkers, rigorous validation. Balancing regulatory requirements with cost-effective approaches, particularly within early-phase studies, requires careful consideration and development.

More advanced imaging modalities, such as magnetic resonance imaging (MRI) and positron emission tomography (PET), can provide insights into the mechanism of action or early treatment effects that cannot be obtained otherwise. Precise imaging design can reduce the number of participants required, reduce unnecessary costs, shorten clinical trial timelines, and enhance data quality through standardized site acquisition and optimized imaging protocol development. Harnessing the expertise of an expert clinical trial imaging vendor in the early stage of trial design can not only help to alleviate any imaging design concerns, but ensures protocol alignment, data consistency, and enhances preparedness for regulatory submission.

The risks of subpar imaging development

Operational, technical, and human factors can all have an effect on the accuracy and effective implementation of clinical trial imaging. Even minor errors can affect participant screening and eligibility, alongside progression decisions, and the overall integrity of data.

Subpar imaging risks include:

• Inaccurate or inconsistent data
• Misclassification of patient response
• Increased result variability
• Reduced statistical power
• Compromised clinical trial endpoints
• Higher operational cost
• Site-to-site variability
• Regulatory rejection or delay
• Loss of confidence in imaging biomarkers
• Trial failure and non-reproducibility

Quantitative imaging biomarkers are now commonly used for subject selection, response assessment, and safety monitoring, but require a comprehensive understanding of bias and precision in order to standardize.

However, site reads have extremely high error rates, with protocol non-compliance often driven by trial complexity and inconsistent workflows, highlighting the importance of clinical trial design which integrates effective and robust imaging assessment protocols early to minimize the possibility of error. This requires expert guidance, as protocols written without imaging feasibility input can misalign with clinical workflow, demand unrealistic scan frequencies, or fail to support quality image acquisition and endpoint consistency.

Why clinical trial imaging needs a seat at the protocol design table

Early integration of imaging experts ensures feasibility, data quality, and regulatory alignment across all clinical trial sites. Imaging experts can assess and facilitate the availability of appropriate imaging modalities across multi-center trials, ensuring site readiness and scanner capability aligned with the patient visit schedule. Imaging experts support the implementation of optimal image acquisition parameters, reducing inter-site variability with protocol-specific imaging documents and site training, designing strategies with regulatory expectations in mind.

Sponsors, especially across oncology and precision medicine, should rethink how and when they engage imaging partners, as effective imaging starts early. An expert imaging vendor is an ally to your clinical trial operations, becoming an integral part of the protocol design working group.

Perceptive Imaging brings nearly 30 years of experience in clinical trial imaging support, with proven industry leadership across a range of therapeutic areas, and a robust team of in-house clinicians and imaging scientists. Partnering with Perceptive ensures operational excellence from imaging protocol development through to endpoint analysis and regulatory submission.

Learn more about Perceptive Imaging Services today, or contact an imaging solutions specialist.

Resources

European Medicines Agency. Strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products – Scientific guideline https://www.ema.europa.eu/en/strategies-identify-mitigate-risks-first-human-early-clinical-trials-investigational-medicinal-products-scientific-guideline

Nature Reviews Clinical Oncology. Opportunities and pitfalls of cancer imaging in clinical trials. https://www.nature.com/articles/nrclinonc.2011.62