Case Studies

Diabetes Post-Authorization Surveillance Study (PASS)

The study objectives were to design a Post-Authorization Surveillance Study (PASS) as a component of a Risk Management Action Plan (RiskMAP), to evaluate the overall RiskMAP success, and to designa PASS as a component of a RiskMAP.The main objective was to successfully negotiate the RiskMAP/REMS under time-sensitive conditions (i.e. peri-approval period). The ideal situation would allow for planning during clinical development (developmental REMS), extensive discussions with internal/external stakeholders, pre-testing of tools in clinical studies or via focus groups, and feedback-driven revisions.

REGISTRAT-MAPI services provided:
  • Evaluation of pre-marketing data
  • Preparing for the pre-NDA meeting
  • Submission of the RiskMAP/REMS
  • Negotiation of the REMS components and approved indications (e.g. type 1 and 2 diabetes)
  • Development, implementation, and management of the prospective observational study and pharmacovigilance plan designed to characterize product use following marketplace introduction
  • Development of a 2-year prospective, longitudinal, match-controlled registry of pregnant diabetic women through delivery, including 6-month infant follow-up (although this was not included in the Risk Management description)
Outcome:
  • Very low rate of MASH among spontaneous reports
  • No increase in MASH incidence in observational study for patients with type 1 and type 2 diabetes relative to that observed in clinical use submitted with original NDA
  • Achieved safe introduction of the product into the marketplace
Critical Sucess Factors:
  • RiskMAP/REMS was successfully negotiated under time-sensitive conditions (i.e. peri-approval period)
  • Knowledge of the key product risk issue
  • Clear definitions (MASH)
  • Epidemiology and characterization of risk attributes
  • Characterization of likely prescribers and implications for risk issue
  • Alignment of organization on objectives (“safe introduction of product”)
  • Education of prescribers, patients, pharmacists was key
    • Who “owns” patient education?
    • Knowledge influences behavior (but does not ensure it)
  • Simple Evaluation Metrics
    • Objective and quantifiable (spontaneous and observational, Rx data, surveys)
    • Defined monitoring/assessment cycle

Paediatric Inflammatory Bowel Disease

A multicenter, prospective, long-term, observational registry of pediatric patients with inflammatory bowel disease (IBD). The objective of the registry is to obtain long-term safety and clinical status information on pediatric patients with IBD.

Challenges / Issues:

  • Site recruitment of pediatric gastroenterologists at largely hospital/academic sites
  • Management of three protocols, including interventional and non-interventional study designs
  • Regulatory compliance in participating countries
  • Patient management as pediatric patients transition to adult care
  • Attrition due to long duration of the Registry
  • Management of patient visit schedules and safety reporting at high enrolling sites

Services Provided:

  • Combination of Remote and On-site Monitoring
  • Ongoing Site Training through Webex as well as face-to-face Investigator and Study Coordinator Meetings
  • EDC and Study Portal for collection of data and dissemination of Registry information
  • R-M managed direct-to-patient Transition Plan to follow patients who leave their pediatric gastroenterologists and who agree to continue participation in the Registry
  • Option of site-managed follow up for patients who leave the care of their Registry physician, but who agree to continue telephone follow up visits with Registry physician
  • Global Safety Reporting
  • Biostatistical and Programming support of Annual Reports

Outcome / Recommendations:

  • Hybrid approach to remote site management and on-site monitoring
  • Linguistic control for Patient Reported Outcome Tools
  • Site refresher training at periodic intervals due to staff turnover and Registry duration
  • Study tools to support critical activities: including patient visit reminders, SAE and Adverse Events of Special Interest reporting instructions, and Transition Plan materials

OSKAR: Observational Study on Reported Outcomes of Treatment with KAletRa® forPatients infected with HIV

HIV treatment implies tolerance issues related to complexanti-retroviral (ARV) regimens that may impact upon patient adherence, resulting in sub-optimal response to treatment. Several studies have shown the impact of the disease and its treatment on health-related (HR) QoL, which is an important predictor ofadherence to therapeutic strategy. The study objectives included: To develop and validate a simplified HIV-specific questionnaire for the clinical management of HIV-infected patients; Marketing department - to promote an ARV drug (KAletRa®); Medical department - to evaluate patient's perceptions of HIV and its treatment

 

Challenges / Issues:
The current available questionnaires are too long for use in daily practice and none are specific for therapeutic management.

Creative Approach and Solutions:
HIV-positive adults treated with an ARV combination including Kaletra® were enrolled in this multicenter, observational, longitudinal study to evaluate Patient-Reported Outcomes.

The study design consisted of an inclusion visit and three follow-up visits (at 3, 6 and 12 months) as part of the routine and usual patient follow-up. A medical questionnaire was filled out by the physician at each visit.

REGISTRAT-MAPI developed the simplified questionnaire after interim statistical analysis of the baseline and 3 months data. Items were selected based on their content and discriminant properties. The simplified questionnaire was then administered at the 12 months visit.

Lessons Learned / Outcome:

The simplified questionnaire included 12 items:
  • 3 HR QoL scores (physical well-being, psychological well-being and global HR QoL)
  • A score of tolerability (13 side-effects items)
  • A visual analogue scale measuring adherence

The final statistical analysis confirmed the validity of a global score and showed acceptable internal consistency of the physical, psychological and global scores; both the marketing and medical expectations were attained.

The HIV-SQUAD® was born (HIV - Symptom Quality of life Adherence).

RADIUS

A prospective, observational study designed to collect and document the patterns of use, effectiveness and safety of DMARD treatments currently used in the management of rheumatoid arthritis.

Challenges / Issues:

  • Range of research experience at sites
  • Site attrition
  • Patient attrition
  • Data submission frequency & accuracy / query resolution
  • Regulatory Compliance

Study Design:

5-year prospective, observational study to collect and document patterns of use, effectiveness and safety of DMARD treatments currently used in the management of rheumatoid arthritis
  • 780 US Sites
  • 10,000 Patients
    • 5,000 exposed to an anti-TNF
    • 5,000 enrolled as a comparator cohort receiving other DMARDS
  • 8 year data collection period

Services provided by REGISTRAT-MAPI:

  • Study materials (develop, distribute, update, collect and track)
  • Enrollment / Regulatory Binder and content
  • Investigator Agreements / Contracts, W9
  • CRFs (all visits included HAQ)
    • Baseline: 7 pages
    • Follow-up: 6 pages
  • CRF and SAE Report Form instructions
  • Withdrawal Form: 1 page
  • FAQs / Tip sheets
  • Site training
    • Annual Investigator Meetings
    • Webex / telecons

Lessons Learned / Outcome:

 

Recommendations:

  • On site & remote monitoring
  • Collection of blinded Informed Consent Forms
  • SAE reconciliation
  • Study tools to ensure consistency and accuracy of data
  • Sharing best practices / empowering the Study Coordinators
  • Training