Setting up a clinical trial is not simply an operational exercise. Decisions made before the first site is activated determine what the study can demonstrate, how efficiently patients can be recruited, and whether the resulting data can support the regulatory pathway.
Many of the most expensive problems can be traced back to decisions that appeared minor when the trial was being designed.
Endpoint selection is often treated as a detail to confirm after the rest of the study design is set. It is not. The primary endpoint defines what the trial will demonstrate. If it cannot be measured consistently across sites, or does not align with regulatory expectations for the indication, the trial data may not support the intended regulatory claim.
This is one reason why indication selection should happen early in clinical development. The indication, target population, endpoint strategy, and regulatory pathway are connected decisions. Choosing one without considering the others creates problems that become increasingly expensive to correct as development progresses.
FDA and EMA requirements for the evidence supporting an endpoint can differ, particularly where surrogate endpoints or additional confirmatory evidence are involved. For programs seeking authorization in both markets, endpoint strategy should therefore be discussed with both agencies before the protocol is finalized.
This is where scientific advice procedures earn their cost. The FDA’s guidance on formal meetings provides a framework for sponsors to discuss development questions with the agency. In Europe, EMA Scientific Advice can cover questions including endpoint selection, study design, statistical methodology, target populations, controls, and overall development strategy.
For companies entering the European regulatory system for the first time, engagement does not necessarily need to begin with a full Scientific Advice procedure. We have explained separately how early-stage biotech companies can first engage with the EMA and which questions are useful to clarify before moving into a formal procedure.
Regulatory advice does not guarantee the outcome of a future marketing authorization application. EMA, for example, describes Scientific Advice as prospective and “not legally binding”. Its value is in giving sponsors regulatory input while the development strategy and study design can still be adapted.
Endpoint definitions need to travel across sites and countries without losing precision.
If an endpoint depends on a specific imaging read, laboratory assay, clinician-reported scale, or combination of measures, the procedures used to collect that endpoint need to be applied consistently across the study.
Standardized procedures, training, calibration, central review where appropriate, and clear endpoint definitions all help reduce variability between sites and strengthen the interpretability of the resulting data.
For global programs, the objective is therefore not simply to choose the endpoint that is easiest or fastest to measure. It is to select an endpoint strategy that is scientifically meaningful, operationally reproducible, and capable of supporting the intended regulatory pathway.
Cost matters when selecting countries and sites, particularly for an early-stage company working within a defined financing runway. But cost per patient is only one part of the economics of running a clinical trial.
The more useful question is what it will cost to recruit the required patients, at appropriate sites, within the required timeline.
Patient availability, recruitment speed, investigator experience, site readiness, and regulatory suitability can all affect that calculation.
A country may offer attractive per-patient costs but limited access to the patient population defined by the protocol. Another may appear more expensive on a site budget but offer experienced investigators, established referral networks, and stronger recruitment potential.
Recruitment speed is particularly important because trial duration itself has a cost. A lower-cost site that enrolls slowly may ultimately offer less value than a site with a higher initial budget but reliable access to eligible patients.
Geography also needs to fit the regulatory strategy. Foreign clinical data intended to support a US marketing application must meet applicable FDA requirements.
For US development programs, the FDA requests the enrolment of a representative population of the country. This includes patients of the same ethnicities found in the US.
The strongest geographic strategy needs an eligible patient population, competing trials, recruitment assumptions, investigator experience, regulatory requirements, operational complexity, and cost as part of the same decision. This produces a more meaningful comparison than country-level cost alone.
Scientific relationships and investigator reputation are valuable starting points for site selection. Experienced investigators can bring therapeutic expertise, established referral networks, and credibility to a development program.
The next step is to confirm that the site also has the patient access, infrastructure, staffing, and clinical trial capabilities required by the protocol.
This is particularly important in early-phase studies, where trial execution can involve specialized infrastructure, intensive monitoring, rapid safety reporting, investigational product management, pharmacokinetic sampling, and tightly controlled treatment procedures.
A structured feasibility assessment allows sponsors to evaluate these capabilities before study initiation.
Under ICH E6(R3) Good Clinical Practice, investigators should have appropriate qualifications and adequate resources for the trial, while sponsors retain responsibility for appropriate oversight of trial activities.
Patient access deserves particular attention. A recognized expert may have extensive scientific knowledge of an indication but a limited pool of patients who meet a particular protocol’s eligibility criteria.
Infrastructure should be assessed in the same way. For a relatively straightforward protocol, standard site capabilities may be sufficient. More complex studies may require specific pharmacy procedures, laboratory turnaround times, equipment, staffing coverage, investigational product controls, or the ability to perform assessments within narrow time windows.
Site feasibility assessment gives the sponsor and site an opportunity to prepare. A capability that is not currently in place does not necessarily make a site unsuitable if it can be addressed appropriately before activation.
This is an important distinction. The purpose of the feasibility assessment is not simply to exclude sites, but to understand what each site needs in order to execute the protocol successfully.
Site readiness then continues after activation. FDA’s risk-based monitoring guidance emphasizes sponsor oversight and monitoring approaches focused on risks to participant safety and data quality. We have discussed this further in our article on risk-based monitoring of clinical investigations.
Endpoint strategy, geography, and site selection are closely connected. The strongest clinical trial plans consider them together rather than as separate operational decisions.
A strong clinical development strategy connects these decisions early, alongside indication selection, regulatory requirements, study design, and the broader development plan.
For example, changing the endpoint can change the assessments a site must perform. Changing the inclusion criteria can change the size and geographic distribution of the eligible patient population. Changing countries can introduce different regulatory, ethics, contracting, and operational requirements.
This is why these decisions benefit from being considered together.
For early-stage companies in particular, this does not mean that every detail needs to be finalized before clinical planning begins. It means identifying the decisions with the greatest downstream impact and bringing the appropriate scientific, regulatory, and operational expertise into those decisions early.
Gouya Insights supports biotech, pharmaceutical, and medical device companies from early clinical strategy through protocol development, regulatory submissions, study setup, and trial execution. You can explore our clinical development services or contact us to discuss the setup of an upcoming clinical trial
References
1. U.S. Food and Drug Administration. Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products. Final Guidance for Industry. August 2026.
2. European Medicines Agency. Scientific advice and protocol assistance. EMA.
3. International Council for Harmonisation. ICH E6(R3): Guideline for Good Clinical Practice. Principles and Annex 1 effective in the EU from 23 July 2025.
4. European Medicines Agency. Clinical Trials Information System. EMA.
5. U.S. Food and Drug Administration. A Risk-Based Approach to Monitoring of Clinical Investigations: Questions and Answers. Guidance for Industry.
About the Author
PD Dr. Ghazaleh Gouya-Lechner is the founder of Gouya Insights and a cardiologist with over 20 years of hands-on clinical practice. She has worked across clinical development, regulatory strategy, and pharmacovigilance for both pharmaceutical and medical device companies. In 2017 she founded Gouya Insights, a CRO supporting early-stage biotech and medtech companies through clinical trials and drug development.
Nora holds degrees in law from Janus Pannonius University and in pharmacy from Semmelweis University, combining legal and scientific expertise. She is a certified Data Protection Officer with hands-on experience supporting GDPR compliance and contractual safeguards for biotech and pharma clients. With over 20 years in clinical research, she brings a pragmatic, risk-aware approach to data protection in global trials
