What is clinical trial design?
Clinical trial design is the process of planning and structuring a study to ensure the quality of clinical data. It includes protocol development, population selection, site choice, a monitoring plan, a data-management strategy, and statistical analysis. This is the key preparatory phase for any medical-device clinical-trial project.
Objective and scope of the clinical-trial project
The study must define its objective clearly—for example, confirming diagnostic performance, comparing the device with alternative solutions, or assessing new functionalities. The scope should cover standard conditions of use and potential boundary scenarios, taking into account the influence of clinical practice on outcomes.
Following the adoption of ICH E6(R3) Annex 2, clinical trial design should also consider the use of decentralised trial elements (Decentralised Clinical Trials, DCT), pragmatic study elements, and Real-World Data (RWD). At the study-design stage, the sponsor should assess whether telemedicine visits, Digital Health Technologies (DHT), electronic informed consent (eConsent), or data derived from Electronic Health Records (EHR) are scientifically justified, proportionate to the level of risk, and appropriate for achieving the study objectives.
Designing population selection and eligibility criteria
Precisely defined inclusion and exclusion criteria are critical for representative results. Demographics, health status, comorbidities, and treatment history must all be considered. An effective recruitment strategy increases the chances of finishing the trial on schedule.
Designing investigational-site selection
Choosing suitable sites should be based on their experience, access to the target patient group, and technical resources. The selection process is supported by an assessment of site qualification and a feasibility analysis in the specific clinical setting.
Incorporating device characteristics into study design
Every design should include a device description, its MDR classification, intended clinical use, and known technological limitations. Pre-clinical data and previous performance results directly influence study assumptions.
Study description as part of clinical-trial design
The description must provide the scientific rationale, randomisation details, blinding (if applicable), sample size (per power analysis), and timeline. Plans for handling protocol deviations and unforeseen situations should also be included.
Designing the monitoring plan and data-management system
The project must incorporate a clear clinical-trial monitoring plan and a data-management strategy—both for eCRF systems and paper records. Consistency with the requirements in clinical-trial data management is essential, including quality control and auditability.
For studies incorporating decentralised elements, the monitoring plan and data-management strategy should address multiple data sources, including eCRF systems, Electronic Health Records (EHR), wearable devices, mobile applications, and other Digital Health Technologies (DHT). In line with ICH E6(R3) Annex 2, sponsors should ensure appropriate data quality, completeness, traceability, and the timely flow of safety information, regardless of where study procedures are performed.
Designing risk assessment and the statistical-analysis plan
The design should identify risks, describe mitigation measures, and outline adverse-event reporting. The statistical section must contain the data-analysis plan, rules for handling missing data, and interim-analysis procedures. Further details are available in statistical analysis of clinical trials.
Ethical aspects of clinical-trial design
Every clinical-trial design must comply with the principles of Good Clinical Practice (GCP), including the latest ICH E6(R3) guideline, ISO 14155:2022, and the Declaration of Helsinki. The informed-consent process must be transparent, voluntary, and comprehensible. Detailed information belongs in the investigator brochure and participant information sheets.
Documentation and submission within study design
The submission package for competent authorities must include the full study plan, investigator brochure, informed-consent forms, and participant-insurance documentation. All documents must meet notified-body and regulatory requirements, in line with clinical-trial reporting procedures.
How Pure Clinical Supports Clinical Study Design
Pure Clinical supports sponsors of clinical investigations of medical devices in planning and designing studies in accordance with applicable MDR, ISO 14155:2022, and relevant GCP requirements. The scope of support covers key elements of study design, documentation, and processes required for study preparation and conduct.
Depending on the project scope, support may include:
- Study objectives and protocol – defining study objectives and developing the structure and key elements of the study protocol.
- Study documentation – preparation of the Investigator’s Brochure and Informed Consent Forms.
- Feasibility and site qualification – assessment of study feasibility and identification and qualification of suitable study sites.
- Recruitment and methodology – defining participant eligibility criteria and appropriate study methodology.
- Data management and monitoring – designing data management processes and planning study monitoring activities.
- Submission documentation – support with compiling and reviewing documentation required for submission to the relevant authorities and ethics committees, in accordance with applicable requirements.
Pure Clinical supports sponsors in translating study objectives into an appropriate protocol structure, documentation, and operational processes, taking into account regulatory requirements and the characteristics of the investigational device.
FAQ
How does the design of a clinical investigation begin?
The design process starts with defining the objective of the study, the target population, and the recruitment strategy. A key document is the clinical investigation protocol, which outlines the study methodology, endpoints, and the statistical analysis plan.
What should a well-prepared clinical investigation protocol include?
The protocol should include a scientific rationale, a description of the device, inclusion and exclusion criteria for participants, a study timeline, detailed procedures, and the statistical analysis plan.
Who is responsible for designing a clinical investigation?
What input data are needed to design a clinical investigation?
The design requires preclinical data, device classification, existing clinical evidence (if available), a description of the target population, and a defined risk profile along with regulatory requirements.
What are the most common mistakes in clinical investigation design?
Common issues include vague study objectives, underestimated sample size, unclear eligibility criteria, and non-compliance with MDR, Good Clinical Practice (GCP), or ISO 14155 standards.