Completing clinical study enrollment

Next steps for your clinical study

Great job on completing enrollment! Reaching this major milestone is a big accomplishment as it marks the start of the data collection stage of the study. After enrollment, there are on-going tasks to tackle.

Subject retention

Patients are well within their rights to withdraw from a study for any reason, but there are ways to foster a subject-friendly study environment to help promote subject retention. Minimize subject burden by allowing them to meet with study staff virtually or during extended hours. Depending on the location, some sites may help coordinate transportation for on-site visits. Patient reported outcomes should be collected in a way that is tailored to the subject population. For instance, an older subject population may prefer paper questionnaires to electronic surveys. Sending reminders to attend follow-up visits or to take medication might reduce subject non-compliance with study procedures. Throughout the study, remind the patient that their involvement is important and appreciated. Also, by offering patients the opportunity to provide feedback, patients feel their perspectives are valued and it can help identify trends or areas that should be changed.

Product shipment

In addition to keeping track of any product shipments during the study, sponsors should also be ready to receive any returned product. The site may send back any unused, expired, or damaged product. In studies for implanted devices, the site may need to send explanted devices and samples for manufacturer analysis. When commercial products are used in the study, if there is a recall, it will need to be communicated to the sites and regulatory agency(ies).

Data management

The bulk of work after enrollment is managing clinical data and medical imaging. Upon receiving data, the data coordinating center should review the data for safety concerns and completeness, generating queries as needed. Depending on how the data are submitted, it may need to be entered in a database. The data coordinating center should track where the data and images are in the process (i.e., received, reviewed, archived). Based on the statistical analysis plan, interim analyses may be performed at pre-determined timepoints throughout the study. Data may also need to be prepared for submission to a data safety monitoring board (DSMB) or a clinical events committee (CEC).

Monitoring

The clinical study will be monitored periodically according to the monitoring plan to verify the protection of human subject rights and well-being, data integrity, and compliance with clinical protocols and relevant regulatory requirements. Based on the study and location, monitoring may be on-site or remote . To reduce bias, monitors, independent of the site and sponsor, should be selected. Particularly for blinded studies, the use of independent monitors will mitigate risk of sponsor unblinding. Regardless of method, monitoring reports should be reviewed by the sponsor to check for quality monitoring and respond to any concerns. For more about monitoring, read our blog and whitepaper.

Noncompliance and deviation follow-up

Monitors, auditors, or other sources may observe potential noncompliances or deviations. The sponsor should then plan and take corrective action as needed. This may include retraining, increasing monitoring activities, or providing increased oversight. The noncompliance/deviation and corrective action must be documented and reported to the necessary parties as appropriate.

Adverse event management

Adverse events could occur at any time. The sponsor and the site must be prepared to respond quickly to adverse events and report to the relevant parties as required. Good data management can save time collecting the necessary documents. Depending on the seriousness of the event, data and reports from independent reviewers of adverse events such as clinical events committee (CEC) and data safety monitoring boards (DSMB) are reviewed and sent to the ethics committee and regulatory body. If study pausing and stopping criteria are met, then the decision of the DSMB should be communicated with the sites , IRB/EC, and regulatory authorities.

Maintaining compliance

Throughout the study, approval from the institutional review board (IRB) or ethics committee (EC) and regulatory body will need to be maintained. The reports required for maintaining approval may differ based on local regulations. The EC or IRB will review study progress at intervals determined upon initial review of the protocol that are based on the risk level of the investigational product or intervention. In the United States, IRBs are required to review a study at least once per year per 21 CFR 56.109(f). FDA guidance recommends that IRBs request a summary of study progress including patient status, updated investigator’s brochure, current versions and any proposed modification to study documents, and safety reports.

For regulatory authorities, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Guideline E2F outlines the standards for an annual Development Safety Update Report. This guideline incorporates national and regional requirements for the US Investigational New Drug Annual Report and the EU Annual Safety Report. The Japan Development Safety Report is prepared according to the ICH E2F guidance, but also contains additional Japan-specific elements.

In the United States, regular progress reports (at least yearly) are required for Investigational New Drug (IND) and Investigational Device Exemption (IDE) clinical studies. FDA has recommended outlines for these reports on their website for IND and IDE studies. For significant risk IDE studies, the sponsor must submit a current list of names and addresses of all investigators every 6 months per 21 CFR 812.150(b)(4). A waiver may be granted to include this information in the annual progress report instead of every six months.

As the study progresses, there could arise ideas to optimize study operations or improve patient safety. Especially in pilot and early-stage clinical studies, amendments and modifications to plans and procedures may be needed. Amendments are submitted to the proper governing bodies for approval, and after an amendment is approved by the regulatory body and EC or IRB, the site will need to be re-trained. For applicable clinical trials registered on ClinicalTrials.gov per 42 CFR Part 11, study information must be verified annually. Changes in study information and status must be updated on the site as well.

Communication records

“Relevant communications” are considered essential documents according to ICH Good Clinical Practice (GCP). This includes emails, meeting/call notes, and letters regarding trial administration and conduct, non-compliance, and adverse events. It is much easier to save these communications as they happen instead of searching for them before study close-out.

Conclusion

In conclusion, study management after enrollment is essential for the success of a clinical study. CROs can be leveraged at any point of the study to help with one or all of these after-enrollment tasks.

MED offers a variety of clinical trial services and is a full-service CRO. We have over 40 years of experience designing and executing clinical trials, ranging from early feasibility studies to multinational, controlled pivotal trials to post-market registries.

Contact us today to start your project discussion!
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