Case Study: Timely Communication within Clinical Trials is Essential for Success
How effective use of text, notifications, email, fax, reports, and alerts enable us to connect with hundreds of clinical study participants and personnel.
- Duplication of Screening/Registration and Randomization via integrated Interactive Web and Voice response systems
- On-Screen and Voice notifications embedded in our applications to direct site users to enter timely data that impels subjects’ progress through the study
- Real-time online reports for study operations personnel, pharmacists and CTM managers
- Custom reminder and documentation emails and faxes, designed for study personnel with blinded and unblinded roles
- Automated guidance in the system that diminished time delays and errors
To communicate study events and real-time subject status using flexible and automated custom reminders, alerts, notifications, instructions and reporting, in order to achieve per protocol 6 hour “registration-to-randomization and dosing” window, with no delays or errors.
The short timeline between initial presentation of subjects and enrolling / dosing eligible subjects to the study was efficiently managed with extensive automation. By using collaboratively well-designed IWRS & IVRS applications and by utilizing and customizing many modes of communication, we were able to keep personnel in the clinical loop at all times and ensured maximum enrollment and error-free clinical activities.
- Phase III, stratified randomization, double-blind, placebo-controlled, parallel-group, study of IMP as compared to placebo at 1:1 ratio
- Therapeutic area: infectious disease
- Indication: necrotizing soft tissue infections (NSTI)
- Approximately 60+ sites in the United States
- 600+ Clinical personnel
- ~290 subjects
- Individual Patient participation was up to 29 days, with 3 month follow-up and termination
- Study duration was anticipated to be 24 months, FPI-LPI
IVRCC systems collected screening and registration information based on preliminary clinical diagnosis of NSTI and initial determination of inclusion/exclusion criteria prerequisite. Screening lasted until study drug administration.
Study drug administration took place during or after Standard of Care (SoC) surgical procedure, when diagnosis of the NSTI was surgically confirmed, but no later than 6 hours from clinical diagnosis of NSTI and the decision at the study site for urgent wound exploration and SoC surgery.
Subjects scheduled for urgent SoC surgical intervention were randomized to IMP/placebo IV administration within 6 hours of initial screening/registration and enrolled to study and dosed only when diagnosis of the trial NSTI was surgically confirmed.
- Short timelines (6 hours) between subject screening/registration where initial clinical diagnosis of NSTI and decision for urgent SoC surgery occurred
- Final confirmation of NSTI was determined at surgery
- Real-time stratified randomization assignment was predicated on recording dosing information and confirmation for previous subjects at the site.
- Protocol indicated that a pharmacist would be constrained from reconstituting study drug until after final NSTI diagnosis was confirmed at surgery, in order to conserve drug, clinical resources, and to maintain balance of stratified randomization/treatment arms
- Timely IMP preparation, with the unblinded pharmacists providing IV preparation based on body weight
- Study procedures required 24/7/365 availability
- Without real-time subject status updates over this short period of time and between a sizable clinical study team, there could have been significant delays, resulting in lost subjects
- Poor, restricted or unpredicted unavailability of Wi-Fi access could present an issue, considering the short timeline for subject screening to surgery/dosing
IVRCC Solutions to Meet Challenges
Since Wi-Fi access in hospital/clinic surgery locations is not always a guarantee, a suitable interactive voice backup system (IVRS) to be able to randomize and dose per protocol was necessary.
IVRCC’s duplicate interactive web and voice subject screening applications were available to register and screen subjects in the event of poor Wi-Fi access or study coordinator preference. Inclusion/exclusion and stratification information was collected in IVRCC’s systems to start the 6-hour clock to potential dosing.
Randomization was performed via IWRS or IVRS. If “Stratification Locked” was noted on screen or by voice, the site user was notified to complete subject dosing status for previous subjects to unlock the ability to randomize the current patient. Coordinators also received daily emails listing subjects for whom dosing had not been recorded as of early that morning.
Surgical confirmation of NSTI was required to be recorded through IVRCC’s interactive systems, with on-screen and voice instruction reminders. This confirmation allowed subjects to be enrolled to the study and dosed. Subjects whose NSTIs were not confirmed in surgery were screen failures and did not receive dosing. Unblinded Pharmacists received emails and faxes reporting the non-confirmation with instructions to discard any drug that had been prepared for that subject. “Unused” randomization codes were returned and “reused”, thus ensuring that the 1:1 IMP:placebo treatment ratio would be sustained.
Real-time alerts, notifications, instructions, reminders and reports for numerous engaged clinical study personnel were essential to ensure efficient and appropriate randomization, dosing and CTM management.
The automated communication functions through every step of the study apprised relevant clinical study personnel of the status of subjects within the study. IWRS web pop-up instructions and IVRS voiced responses guided clinical personnel to provide all information needed to correctly screen, register, randomize, and dose subjects per protocol. Roles and permissions determined the extent of study subject detail communication that was available to certain study personnel. Potential errors and delays were mitigated thanks to the built-in automated communication features designed to be generated through both the IWR and IVR applications.
Specific Communication Features
Automated Notifications, Reminders, Alerts via email, fax, and within study web and voice applications (web pop-ups or voice call-outs), User Manuals, field edit checks, and final confirmation of entered data to prevent incorrect, invalid or missing data.
User Manuals: Overview instruction to blinded study coordinators and other study personnel on how to use system, self-register, update password, register, randomize and update subject information. Unblinded for Pharmacist/CRA Monitors for managing manual replenishment to or removal from inventory due to breakage, temperature excursions, and non-use.
Event-triggered emails and faxes to site-specific Unblinded Pharmacists provided randomization and IVRCC system-calculated dose determinations, including number of vials needed, based on the subject weight captured at IVRCC’s screening/registration pages.
Event-triggered emails to site-specific unblinded CRA monitors and pharmacists were provided to initiate site supply replenishment when programmed low-supply limits occurred.
Daily emails provided blinded study personnel (Blinded Study Coordinators, Sponsor/Blinded Monitor Roles) a list of subjects who had not yet had dosing status recorded into the IWR or IVRS for their site-specific subjects.
When invalid information was entered, or information was missing, on-screen or telephone instructions appeared automatically to remind users to record data that would allow further progress in the study.
When the study coordinator entered the final surgical confirmation of NSTI diagnosis, separate customized email notifications and/or faxes were sent to blinded Study Coordinators, confirming that NSTI had been recorded.
Real-time Web Reports and activity confirmation pages displayed up-to-date progress of data entry to blinded clinical personnel.
Custom-designed notification emails and/or faxes, triggered by milestone events, were sent to blinded and unblinded roles as appropriate when a subject was registered, randomized and when subjects were confirmed /not confirmed as NSTI subjects and if/when dosed. Study summaries were updated in real-time.
Because our system detected when emailed or faxed notifications were occasionally rejected as “undeliverable”, IVRCC was able to personally notify sites of the failures so that apparent fax machine malfunctions or incorrect email addresses could be resolved.
Why was IVRCC the right choice for this study?
IVRCC’s 25+ years of building interactive applications for clinical trials ensured high quality recommendations and innovative design suggestions for the specific challenges of this study.
We combined the most suitable modes of communication, utilizing our wide array of tools for web and voice based systems to achieve efficient real-time results, while lessening the burden on clinical personnel.