Site Visits 101: Visits With Participants, From Prescreening To Completion

By Susan Swonger, clinical research consultant and senior clinical research coordinator, and Daniel Fox, MPH, Ph.D., founder/CEO, Clinical Research Payment Network, Land of Lincoln Clinical Research, and DiversiTrials

Clinical trial participants attend many site visits, each with a distinct purpose. Every trial comprises a series of fundamental visit types, targeted objectives, and anticipated outcomes that progress study milestones through the clinical trial life cycle. From the first interaction to the final thank you, the clinical trial process has established and structured visits to ensure trial participants are enrolled in a well-planned and executed trial.

In this follow-up article to “Site Visits 101: Visits Before, Without, And After Trial Participants,” discover all of the site visits that include patients, from the time they are prescreened to — if enrolled — the time they complete the study.

Prescreening Visit

OBJECTIVE: Although it may be an initial phone conversation, prescreening visits comprise site staff introducing themselves to potential candidates during routine doctor visits and discussing the opportunity to participate in a clinical trial. Staff may ask trial participants follow-up questions about details that are not included in medical records to assess eligibility and describe the study’s purpose, requirements, procedures, or potential risks and benefits. By the end, prescreening visits are designed specifically to identify interested trial candidates who are potentially eligible for formal screening visits.

OUTCOME(s): Candidates will either be eligible and interested or ineligible and/or not interested in trial participation.

BEST PRACTICES: Prescreens are potentially the beginning of a long relationship with a participant and therefore are critical to the proper performance of a trial. To conduct proper prescreening:

1. Clearly communicate: Be sure the trial candidate understands what participation involves, including travel, appointment length, number of clinic visits, trial duration, and risks/benefits.
2. Double check. Be certain: Review medical records carefully, if available, and ensure each candidate meets preliminary qualifications. It’s a terrible feeling to tell a patient “never mind” after you initially tell them they may be eligible for a trial.
3. Respect the screen… and the candidate: Not all patients screened are qualified for the study, and not every patient is interested. It is important to approach prescreening with this mindset.

Screening Visit

OBJECTIVE: Successfully prescreened candidates continue their journey with a screening visit. Screening visits first establish formal informed consent and then collect the necessary samples and data to determine if a candidate is eligible to be a trial participant according to the study’s protocol. Samples may include surveys, radiological assessments, biological samples (blood, urine, biopsies, etc.), and physician assessments.

OUTCOME(s): Screened candidates may be eligible for the trial and therefore move to a randomization/baseline visit. If candidates are not eligible, they are “screen failed” and discontinued from further trial participation. Screening determinations may not be complete on the day of screening and instead may be determined after receiving lab or biopsy results that are processed and returned days or weeks after a screening visit.

BEST PRACTICES: Successful sites have a series of best practices to enhance screening visits:

1. Check the protocol: Screening visits must strictly follow a protocol’s criteria to ensure that only eligible patients are enrolled. Often in the early phases of a trial cycle, protocol amendments are rapidly implemented. These amendments may change the inclusion/exclusion criteria and consequentially compromise a trial candidate’s eligibility. Be sure to have systems in place to ensure the most current IRB-approved protocol is referenced at all times.
2. Do not “milk”: Sites often face financial incentives to screen as many trial candidates as possible, whether they are or are not qualified. Milking screen failures helps nobody in the system. It's not a unique practice and sponsors often protect themselves with screen failure ratios or caps.
3. Stop ASAP: Sites may also face financial incentives by continuing a screening visit when they’ve already identified ineligibility. To save trial participants unnecessary pain and discomfort, halt all visit activity as soon as a candidate screen fails. It's not worth the money to ask a patient to unnecessarily suffer.

Baseline Visit

OBJECTIVE: Successfully screened candidates proceed to a baseline visit. The baseline visit is established first to randomize a candidate as a trial participant in a trial. As a comparative reference point, the baseline visit maintains the integrity of the study data and analysis.

OUTCOME(s): Baseline visits result in a successfully randomized trial participant who now has preliminary data that serves as a reference point to the trial’s treatments and interventions. Following baseline data collection, many baseline visits result in the first administration of the trial’s treatment or intervention.

BEST PRACTICES: Baselines are crucial for establishing a trial participant’s condition before the study start. To improve baseline visit performances:

1. Order and details matter: Pay close attention to the order of operations in a protocol and the nuances of its requirements. Should participants be sitting for 5 minutes before collecting blood pressure? Do they need to be fasting for their blood draw? Should one procedure be collected before another? Know the protocol well enough to reduce it to practice well before the first scheduled screening visit.
2. Perform tech walkthroughs: There's nothing more embarrassing than performing baseline visits with faulty tech with patients and physicians staring impatiently. As much as possible, test technology in the participant location to make sure it is working seamlessly. In the event of a problem, have all contact information available and know how to request help from technology representatives.
3. No going back: Once an intervention is administered, baseline data will not be available. As a result, be sure to perform complete due diligence on all source documentation templates to make sure every required piece of information is collected.

Progress And Treatment (Intervention) Visits

OBJECTIVE: Randomized trial participants continue their journey through progress and treatment visits. These visits are designed to closely adhere to the current IRB-approved protocol to collect data, discuss with trial participants any changes in health, measure the effect of treatment, assess the change in disease severity or improvement, reconcile any remaining investigational product, and administer the next series of interventions according to the protocol.

OUTCOME(s): Sites will collect the protocol’s required data and record it in the appropriate source documents. Any lab, diagnostic, or patient-reported adverse events (AEs) may be monitored the protect the safety of the trial participant. Finally, trial participants will receive the next series of interventions and schedule subsequent trial visits.

BEST PRACTICES: Sites may adopt a series of best practices for optimal treatment visits:

1. Be prepared: Many clinical research coordinators will agree that treatment visits require substantial amounts of time to prepare documents, coordinate procedures, and prepare resources. Be prepared for trial visits well before the day of occurrence.
2. Details matter: The timing, dosage, and administration method must align with the protocol to maintain the study’s integrity and ensure patient safety.
3. Watch the blind: Many clinical trials plan blinded treatments to eliminate the bias of trial participants or site staff. For example, if a hypertension study is designed to reduce blood pressure and a trial participant’s blood pressure is reducing, staff may suspect that the participant is on the investigational product. Carefully train staff and establish protocols to eliminate chances of breaking a study blind and ensure data collection without bias.
4. Planned redundancy/ backup: The trial must go on with or without a specific coordinator. Adopt “buddy systems” or cohorts of coordinators who can support each other’s trials in the event an employee leaves or is unavailable to work during a scheduled visit.

Follow-Up Visits

OBJECTIVE: Not all trial visits will require treatment or invention. Follow-up visits are designed to collect data according to the protocol and measure the effect of treatment and assess the change in disease severity or improvement without additional treatment or intervention dispensation. Follow-up visits may include general healthcare assessments such as physical exams and vital signs, collection of additional samples such as lab samples, and surveys such as electronic patient-reported outcomes. They are also an excellent time to monitor safety, assess efficacy, and address any new issues or concerns the participant or PI may have.

OUTCOME(s): Follow-up visits result solely in the collection, entry, and documentation of the clinical trial data required by the protocol.

BEST PRACTICES: Visit window: Every protocol has windows of compliance at each scheduled visit. Pay attention to the protocol-specific windows and be mindful of holidays and weekends. Failure to comply with the protocol’s visit window requirements results in protocol deviations.

Unscheduled Visits

OBJECTIVE: What happens if a trial participant experiences an AE or serious adverse event (SAE) and needs to see the PI unexpectedly? What happens if a safety report returns concerning results and requires an additional visit to protect participant safety? In a world of structured protocols and stringent regulations, the unscheduled visit provides the flexibility needed to accommodate the needs of trial performance with the requirements of the protocol and patient safety.

OUTCOME(s): Following an unscheduled visit, site staff will collect additional data and samples as needed by the protocol or the PI to monitor the health and safety of the trial participant and record appropriately in source documentation.

BEST PRACTICES: Although unexpected, unscheduled visits may be managed properly with proper processes:

1. Reporting requirements: It’s important to report unscheduled visits to the sponsors and the IRB. These communications help maintain transparency and regulatory compliance.
2. Know the budget: Unscheduled visit payment structures range from flat fees to paying only for what services are provided. Be sure to communicate unscheduled visit activities appropriately to site finance teams and according to each CTA.

End-Of-Treatment Visit

OBJECTIVE: Trial participants conclude study interventions with an end-of-treatment study, which is designed to conduct thorough and final assessments of a participant’s response to a trial’s intervention and assess any adverse events. End-of-treatment visits may result from early withdrawal (EW) from the study. And, while the end-of-treatment study concludes a trial participant’s study performance, many studies include safety follow-up calls or long-term follow-up events to continue health and safety monitoring.

OUTCOME(s): Whether at the end of the trial or in early withdrawal, end-of-treatment visits result in a trial participant’s discontinuation of study activities and the completed record of all active participant data, results, and trial outcomes. Sites may also discuss and establish long-term follow-up plans with trial participants.

BEST PRACTICES: End-of-treatment is a site’s final chance to accurately collect, enter, and document patient findings. Be sure to follow protocol requirements and document final results in an organized and compliant process.

Let’s Revisit

Site visits are challenging, are customized to every protocol, and risk absolute chaos if they are not managed appropriately. There are, however, routine best practices that are adopted among some of the most successful sites. Stay prepared and organized throughout the clinical trial process. Accurately record data and observations and be sure to communicate with industry stakeholders, especially the trial participants. Finally, remember why we perform research to begin with — to protect the safety and well-being of our trial participants with confidential trial performance, secure data, and successfully reported results that will advance future medicines from the clinical trials we perform to generations of healthier communities.

About the Authors:

Susan Swonger is a clinical research consultant with over 20 years of experience as a clinical research coordinator, rater, and e-TMF specialist. She started her research career as a psychometrician doing Alzheimer’s trials. She is a member of ACRP and supports Save Our Sites as well as diversity in clinical trials.

 

 

Daniel Fox, Ph.D., is the founder and executive of the Clinical Research Payment Network, Land of Lincoln Clinical Research, Save Our Sites Conference and Alliance, and DiversiTrials. He has worked in the translational sciences, from bacteria and animals to pharmaceutical manufacturing, quality control, and clinical site administration, for over 15 years and strives to be a servant community leader to ensure open access to clinical trials for everyone regardless of where they live, what they look like, or how much money they have. Fox specializes in legal and financial translational sciences with a focus on ensuring clinical research stakeholders (sponsors, PIs, site staff, and, importantly, patients) have everything they need, from payments and SOPs to protocols, equipment, and networks, to perform successful quality research and advance healthcare technology as quickly, efficiently, and safely as possible.