Case Study: Detecting Pain During a Hemophilia Treatment Clinical Trial

Pain is a symptom of many diseases and conditions in a wide variety of therapeutic areas and indications. Measuring pain characteristics during clinical trials/studies and healthcare settings can provide critical insight that may increase understanding and improve treatment therapies for pain. 

Because hemophilia is a serious and sometimes life-threatening condition, patients with hemophilia are very compliant about self-reporting clinical study/trial data. Using a novel ediary developed for a hemophilia gene therapy treatment study, one of the data points collected was patients’ reported pain characteristics at specific points during treatment interventions for bleed episodes. 

Collaborating with the client, IVRCC created a complex, interactive, novel, web-based ediary enabling patients to capture details about bleed circumstances, severity and symptoms—including pain experienced during bleed recovery treatments, and regular and on-demand treatment infusions.

Objective

• This study was designed to investigate and monitor the effects on efficacy and safety of systemic administration of experimental gene therapy treatment of adult patients with severe or moderately severe hemophilia B and severe bleeding type.

Study Statistics

• Phase 1/2 interventional
• Male, Adults with congenital hemophilia B classified as severe to moderately severe 
• Completed ~10 patients 
• Multi-center, multiple countries
• Duration of patient participation ~5 years/total data collection per patient

Features

• Patients self-reported their bleed and infusion episodes in detail 
• Novel web e-diary, BYOD
• Patient training, with documentation, and retraining option  
• Patient self-registration
• Seven native language translations
• Patient engagement over an extended period of time with minimal burden on patients 
• Accuracy and completeness and e-diary compliance
• Reporting in real-time, review options 
• e-source data collection

Our Solutions to Meet Study Challenges

Novel e-diary, including custom pain scale

IVRCC and Sponsor/CRO created a pain scale specifically for this study. In addition to capturing data associated with the events and outcomes assessments, the e-diary application was used for tracking characteristics of bleed events and the effect of treatments throughout the study. Pain categories specific to the disease and conditions were identified, utilizing qualitative, quantitative, location and relative descriptors to characterize effects of treatments, and summarized in a patientive Evaluation of Effect 4-point scale: Excellent – Good – Moderate – None for patients to use for pain evaluation. 

Translations

Several languages were required for the sites participating sites. IVRCC interfaced with experienced translation providers through several steps: translation, reverse translation and review by clinical site personnel native speakers, certification and final deployment. Any updates and additions to survey/ediary questions were released rapidly due to IVRCC’s automated translation module for changes in wording and languages.

Patient Self-Registration to the e-diary

After patient eligibility was confirmed, study coordinators generated the patient ID info in the site application. Patients self-registered with personal information for identification and authentication.  Passwords were confidential and could be reset through an automated module or, though rarely needed, IVRCC’s helpdesk.

Training

Upon eligibility and ICF acceptance, patients automatically trained and familiarized themselves with e-diary formatting, content and navigation. Training was documented and follow-up trainings were available as needed during in-clinic visits.

PRN e-diary for Patient Engagement

Because patient engagement was an important factor for the 5-6 years of participation required for patients, a P.R.N. e-diary (pro re nata, “as the thing is needed”) was the ideal type of e-diary to avoid overburdening patients with unnecessary interaction when no recordable events had occurred.   

Reminders for Patient Engagement

The system was set up to send intermittent reminders to patients’ own devices at intervals such that, when combined with in-person clinic visits, high levels of engagement and compliance were maintained. 

Accurate and valid data entry, completeness and high e-diary compliance

Accuracy resulted from training, interactive guidance and complex coded data entry logic. A web-based application, available on patients’ and sites’ own devices, was developed with data entry logic guidance, allowing only valid entries. Patients and sites were sent notifications and real-time instructions identifying areas needing attention. For example, the system did not allow a Bleed Start time to be entered as after an End time for the same event. The coding prevented incongruous (impossible) entries that were incompatible with previous data entries. 

Reporting and Review in Real-time

Reporting: Rescue Infusions and Treatments for Pain and Bleeding

Patients were encouraged to review their own entered data. Red text indicated which entries were incomplete or needed attention.

Read-only access of all patient ediary data was implemented for certain permissioned personnel at sites and for CRO staff. Permissioned study personnel reviewed patient entries during clinic visits with patients, for completeness and additional clarification, helping to maximize patients’ timely and accurate data entry.

Data Management

IVRCC’s system collected, managed and stored diary data utilizing easy-to-use custom web eCRFs, including the patient-reported pain data. IVRCC’s systems integrated with a third-party study database system for patients to pull their personal user ID that study coordinators created there, allowing patients to easily and securely self-register and report outcomes through use of IVRCC’s esource user-friendly IVRCC ediary.

Why was IVRCC the right choice for this study?

IVRCC is an experienced and collaborative partner.

Decades of design experience and collaborative approach result in quality surveys that yield high compliance from patients even in challenging situations, such as need for multiple native language versions, or where there is no internet connection in hospital emergency and operating rooms. When creating novel web based and voice questionnaires and ediaries, IVRCC works closely with clients to ensure ease-of-use and efficiency.

We specialize in providing custom solutions and recommending the best data collection methods for both standard and unique clinical trial circumstances. IVRCC’s original phone Telediary® was an innovation for clinical trials and patient ePRO/ediaries in the early evolution of e-source, non-paper data collection. Our experience with pain ePRO and ediaries in many therapeutic areas and sub-indications allows us to tailor and optimize the design for patients, patients, caretakers and clinicians. 

Sponsor Outcome

FDA Biologics License Approval (BLA) 2022

Investigational product (IP) was approved for patients who use Factor IX prophylaxis therapy or have serious hemorrhage or spontaneous bleeding episodes. This IP is the first and only FDA-approved gene therapy for hemophilia B. As a one-time infusion that offers elevated factor IX levels for years, which is proven to reduce annual bleed rates and reduce/eliminate the need for additional prophylactic therapies, this treatment will generate life changing results: significantly lowering the economic and quality of life burden of hemophilia B. The review of this product was associated with several relevant National Clinical Trials (NCT), one of which was this 5+ year study for which IVRCC provided the technology solutions.