A good protocol is critical to the success of a study. It is important that the Sponsor/CRO spend time in the design of the study and writing the document so it is clear to all those who participate in the study and to the Food and Drug Administration (FDA). Both the Regulatory and the Clinical Groups with the Lead Investigator provide valuable information on the inclusion/exclusion criteria, a possible comparator and the standard practice of medicine. Careful consideration of the inclusion/criteria helps to assure that enrollment will be successful.
The literature is also reviewed for relevant information to help design the study. Data Management reviews the protocol to determine how best to collect the data from the study. They also consider the appropriate database and design the Case Report Forms (CRFs) for data collection. Statistical input is also required for the protocol. The primary and secondary safety and efficacy endpoints are determined along with an explanation of which statistical methods will be applied at appropriate times during and/or after the study is completed. The Biostatistician will also work with Data Management to ensure that the data exported can be analyzed. The Informed Consent Form is created as an appendix to the protocol.
Clinical Site Selection
Clinical site selection is often the key to any successful clinical trial. What are the elements of site selection that will help ensure steady enrollment and good compliance?
- Has the site been inspected by FDA and what was the outcome of that inspection? Is the Investigator on the FDA Debarment List?
- Are there enough clinical sites to meet enrollment timelines?
- Budget constraints may reduce the number of clinical sites at study start-up; however, when enrollment is sluggish, sponsors are forced to add more sites which results in lost valuable time.
- Ensure your pool of candidate clinical sites is robust.
- Consider more clinical sites if inclusion/exclusion criteria is complicated and screening failures will be unusually high.
- Enrollment projections founded on realistic (more conservative) goals rather than best case scenarios will create a positive environment for the entire study team.
- Central versus Local Institutional Review Board (IRB). An example of local IRB would be “University of College” IRB which are often affiliated with a college, university or hospital institution. Western IRB (WIRB) is an example of a Central IRB. A Central IRB can have several advantages over Local IRBs including:
- Shorter review periods leading to faster site activation and enrollment.
- Sponsor may be able to submit documents on site’s behalf saving time.
- Standardized forms and templates.
- Consistency across reviews and reviewers.
- Increased likelihood of familiarity with your medical device and therapeutic area because of the high volume of clinical trials.
- Academic sites tend to require use of their local IRB where private practices are more likely to allow the use of a central IRB. Along with this, clinical trial agreements take longer to execute at academic sites versus private practices.
- Does the study site have the patient population to support the clinical trial?
- Assess the site’s patient volume in your therapeutic area. A prestigious institution may not have the volume of patients to support your medical device. It is important to inquire about patient population during site qualification.
- Investigate the site’s previous and current experience on medical device trials. Information may be available on ClinicalTrials.gov, PubMed or Google Scholar.CAUTION: Assess whether or not there are competing studies that would funnel patients away from your trial.
- Site Training/Staff Availability.
- Does the site have the necessary staff available to execute your clinical trial?
- Is there a dedicated study coordinator?
- Has staff turnover been minimal?
- Will the clinical staff be available for training throughout the study?
- If you are using a teaching institution, will Resident Physicians be staffed on the clinical study? Resident Physicians may be rotated on and off the trial by the Principal Investigator.
- Seasoned versus Inexperienced clinical sites. Seasoned sites may have the expertise you need, but do they have the bandwidth to give your study the attention it deserves? Key Opinion Leaders may not always be the best researchers – it’s important to balance marketing needs versus quality of execution of the clinical study
- Inexperienced sites may require more time and effort. Keep this in mind if a new site is selected.
- Good communication
- Assess communication with a site during the qualification and site selection process. If emails and phone calls are not returned, it may be a precursor to what lies ahead.
- Find the sweet spot for the amount of Sponsor communications and engage each site in how they best prefer to receive information. Emails are great, but our practice is to have phone conversations whenever possible.
- Confirm site’s Standard of Practice does not disrupt study requirements. If Standard of Practice is disrupted, can the site still execute the trial?
- If first enrollment is long after initial site training, re-train the site as soon as possible. Re-training the site will help create momentum for your study and may improve compliance.
- Consolidate study communications to sites.
- Balance quality versus quantity—your study is likely not the only study, so, to ensure your study gets the attention it deserves, make your communications count. Do I really need to send this email? What happens if we wait to implement a new protocol?
- Is our study becoming part of the static (background noise)? If so, enrollment may suffer.
Selecting optimal clinical sites is important to clinical success. Choosing sites that have more positive attributes will pay dividends in the end.
Look for Medical Device Development: Clinical Studies, Part 2, where we will discuss monitoring, clinical data and more.
If you missed the previous post in this series, Medical Device Development: Design Validation and Preclinical, Part 2, you can view it here.
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This post was written accompanied by Mike Grillo, former Senior MRM at NAMSA.