Site-Level Execution In Clinical Trials: Where Systems Break Down

A conversation with Pramrod Ghaytidak, clinical research associate, Torrent Pharmaceuticals

Clinical trial supply performance ultimately depends on execution at the site level. While much of the focus in supply chain design is placed on forecasting, distribution, and investigational product logistics, operational breakdowns during trial conduct can significantly impact supply continuity, accountability, and study timelines.

Challenges such as delayed data entry, protocol deviations, system constraints, and communication gaps between site teams and sponsors can all create downstream effects that influence investigational product flow and trial efficiency. These issues often emerge not from system failure alone but from the realities of day-to-day site operations under increasing study complexity.

In this Q&A, Pramrod Ghaytidak, clinical research associate at Torrent Pharmaceuticals, explores where execution breakdowns most commonly occur at the site level and discusses how these operational challenges can indirectly affect trial continuity and overall study performance.

Where do you most often see a gap between protocol design and what is actually executable at the site level during monitoring visits, and what typically causes that gap?

In my experience, the biggest gap is when the protocol looks fine on paper but becomes difficult to manage at the site level. This usually happens when too many procedures are planned in one visit or when visit windows are very tight.

For example, a patient may need labs, ECG, vitals, questionnaires, doctor review, and drug dispensing all on the same day. At a busy site, managing all this smoothly can be challenging. It can lead to delays, missed timings, or extra pressure on staff.

Another common issue is complex inclusion/exclusion criteria. Sometimes site staff need multiple clarifications before they feel confident screening patients.

Most of these gaps happen because protocol design does not always fully consider day-to-day site workflow. If site teams are involved earlier, many practical issues can be avoided.

These gaps usually happen because site operational input is limited during protocol development. If investigators, coordinators, or field teams are involved earlier, many practical challenges can be reduced before study start, improving alignment between protocol execution and investigational product handling, especially during visit-day supply coordination.

In practice, how do SDV and SDR approaches differ across studies, and where do you see the greatest impact on data quality or risk signals during monitoring?

SDV is mainly checking whether data entered in EDC matches the source documents. SDR is broader; it checks whether the source records themselves are complete, accurate, and support subject safety and protocol compliance.

In practice, SDV helps identify data entry mistakes like wrong dates, lab values, or medication entries. SDR helps detect deeper issues such as missing notes, undocumented adverse events, delayed assessments, or incomplete consent process documentation.

I often find that SDR gives earlier warning signs of site quality issues, while SDV confirms data accuracy. Both are important, but together they provide the most complete view of monitoring risk systems.

In some cases, these documentation gaps directly weaken investigational product accountability and traceability, particularly when administration or storage records are involved, creating downstream risk in reconciliation and inspection readiness.

From your experience, how do EDC and IWRS systems help or hinder day-to-day site workflows, and where do system constraints most often create friction or errors?

EDC and IWRS are very useful when systems are stable and user-friendly. EDC helps sites enter data in real time and resolve queries faster. IWRS helps with randomization, visit scheduling, and IP management.

The challenges usually come when systems are slow, difficult to use, or not aligned with each other. For example, a visit may be completed at the site level, but due to a missing entry in one system, randomization or drug dispensing gets delayed.

Other common issues are password expiry, delayed user access, and lack of proper training. These problems often happen on patient visit days, which creates unnecessary pressure on site staff.

These system constraints directly delay randomization and investigational product dispensing, particularly in studies where supply timing is tightly synchronized with patient visit schedules and site-level inventory availability.

When protocol deviations occur, what are the most common underlying operational or system-level causes you observe during site oversight?

Most deviations do not occur because sites ignore the protocol. Usually, they happen due to operational challenges.

Common reasons include patient scheduling conflicts, missed visit windows, delayed lab reports, incomplete re-consent after amendment, or assessments done outside the required timeline.

Staff turnover is also a major reason. When experienced coordinators leave, new staff may not be fully trained immediately.

Sometimes sites are handling many studies at once with limited resources, so workload becomes a factor. Good planning, regular training, and proactive follow-up can reduce many of these deviations. These deviations could create downstream challenges in investigational product resupply planning, accountability reconciliation, and inventory accuracy later in the study.

Across SQV, SIV, ongoing monitoring, and close-out visits, where do you typically see the highest risk of operational breakdown — and what drives those failures?

In my experience, the highest risk is usually during ongoing monitoring visits. At the beginning of the study, during SQV and SIV, sites are generally prepared and focused.

Once enrollment starts, the real workload begins. This is when delays in data entry, pending queries, incomplete source documentation, drug accountability issues, and missed training updates start appearing.

Close-out visits also carry risk, mainly around unresolved queries, missing documents, and final reconciliation. But the most pressure is usually during the active phase of conducting the study. This active phase is also where risks to investigational product accountability, reconciliation accuracy, and supply documentation completeness are most likely to emerge.

How is data integrity (e.g., ALCOA++ principles) actually enforced at the site level during real-world trial execution, and where does it most often break down?

Data integrity is maintained through training, proper documentation, audit trails, monitoring review, and controlled system access. At the site level, it means recording data correctly, on time, and by the right person.

In real practice, the biggest issue is delayed documentation. Procedures may be completed on time, but notes are entered later, which can create accuracy concerns. Missing signatures, unclear corrections, or incomplete source notes are also common gaps.

Electronic systems help through audit trails, but good habits at the site level are still the most important factor. When staff understand that documentation is part of patient safety, data integrity becomes much stronger. This is also critical for investigational product traceability and regulatory inspection readiness, particularly in clinical supply audits where documentation integrity directly supports chain-of-custody verification.

What role does communication between the CRA, site staff, sponsor, and vendors play in successful site execution, and where do communication gaps usually appear?

Communication plays a very important role in smooth trial execution. Even when systems and processes are well designed, poor communication can create delays and confusion at the site level.

The CRA often acts as the link between the site, sponsor, and different vendors such as central labs, IWRS support, or courier teams. Clear and timely communication helps sites understand expectations and resolve issues quickly.

Common gaps usually happen when updates are shared late, responsibilities are unclear, or different teams provide conflicting instructions. For example, if a lab kit change is communicated late, patient visits may be affected.

Regular follow-up, clear escalation pathways, and practical communication with site staff help prevent many avoidable issues. Communication gaps also directly influence supply-related execution decisions such as kit replacement timing, resupply coordination, and depot-level inventory management.

What are the early warning signs that a site may begin struggling operationally during a study, and how can they be addressed early?

There are usually early signs before a site starts facing major operational problems. Common signs are delayed data entry or an increase in pending queries. Others are repeated minor documentation errors, delayed responses to emails, or difficulty scheduling monitoring visits.

Frequent staff changes or reduced engagement from the coordinator can also indicate upcoming challenges. Sometimes patient retention issues or missed visit windows begin appearing early.

When these signs are noticed early, timely support can make a big difference. This may include refresher training, more frequent CRA follow-up, clearer action plans, or direct discussions with the investigator and site team. These early indicators can also signal emerging risks to investigational product compliance, site-level accountability, and overall supply execution stability.

About The Expert:

Pramod Ghaytidak is a clinical research associate with over three years of experience managing and monitoring Phase 1–4 clinical trials and post-marketing studies across multiple therapeutic areas. He has hands-on expertise in site qualification, initiation, routine monitoring, remote oversight, and closeout activities, with a strong focus on protocol compliance, data integrity, patient safety, and regulatory standards. His experience includes source data verification, investigational product accountability, site feasibility, ethics submissions, and collaboration with sponsors, CROs, and investigator sites. Pramod is particularly interested in strengthening site-level execution, operational efficiency, and quality systems that support successful trial delivery. He is currently based in Ahmedabad, India.