CTMG’s CEO, Anton-Lewis Usala, MD returned to Washington DC this week to present at the Food and Drug Law Institute’s premier Annual Conference, focused this year on Recent Trends in Data Integrity Compliance and Enforcement. Dr. Usala profiled the key strengths of the SSRO approach – Adaptive Investigative-Site Management (AIM) – in ensuring that high quality human clinical data is generated efficiently from numerous qualified patients at each site using design-reviewed protocol-specific processes.
Dr. Usala was included in a panel of invited FDA, CRO and Legal experts1 asked to review data integrity issues and offer solutions. His presentation and subsequent discussion highlighted specific examples of data quality issues that were identified, investigated and overcome using the unique SSRO quality system review processes developed by CTMG. With the SSRO approach, the capture of study data as intended is verified through real-time review at study sites as patient visits are managed by SSRO clinical personnel working side by side with each Business Associate Principal Investigator.
Outcomes of two studies in distinct therapeutic areas were provided to show the power and necessity of this approach. Non-compliant electronic data capture for a phase 3 ADHD study provided uninterpretable study data from 15 of 16 non-AIM sites while a single SSRO AIM site with design-reviewed systems in place detected, verified and worked around this potentially fatal error in study design to enroll one quarter of the required study population. The SSRO, recognizing the flaw in the Sponsor’s EDC system, independently had their staff hand enter data into paper CRFs in parallel with the Sponsor’s EDC system, to protect the integrity of study data obtained at the SSRO-managed physician site. Only the AIM site data were acceptable for Agency review of the study.
In a pivotal phase 3 study addressing a high-risk cardiovascular condition, a synergistic Adaptive Investigative Site Management solution was proposed by the SSRO at the time the Sponsor’s RFP was sent out to prospective CROs. The SSRO proposed bringing up 15 of their Network Physician Sites to enroll and follow all 240 U.S. patients, with the traditional CRO providing all usual other services. The Sponsor decided to contract for only 7 SSRO sites to enroll half the U.S. patients (120) in six months, with the CRO contracted to enroll and follow the other 120 patients from their originally proposed 80 sites in six months.
The seven SSRO sites enrolled 125 patients in 4.5 months. The 80 traditional CRO sites enrolled only 100 patients, and 80% of their patients in one study arm were enrolled in violation of the complex I/E criteria. Proactively recognizing the need for experienced medical personnel to ensure these complex I/E criteria were met, the SSRO quality systems approach used seven different individuals to review each patient’s screening data before internal approval was given to randomize the subjects. The 125 subjects enrolled by the seven SSRO sites were 100% compliant with the protocol I/E criteria. The adherence to study timelines and rapid, superior quality data provided by the SSRO sites saved the Sponsor millions in direct costs, and will enable hundreds of millions in additional incremental sales revenue by accelerating FDA review and approval.
In both studies, CTMG subject matter expert assessment of study compliance and patient safety issues combined with persistent presentation of these issues to sponsor or study CRO personnel was required to successfully address and cure or prevent the problems identified. Rapid identification and correction of data integrity and patient safety issues preserved these requirements when fundamental study deficiencies threatened study and product success.
1Panel members included the following in addition to Dr. Usala:
• George J. Serafin – National Managing Director, Life Sciences and Health Governance, Regulatory and Risk Strategies, Deloitte and Touche, LLP.
• Cathy Burgess – Partner, Alston & Bird, LLP
• Paula R. Katz, JD – Director, Guidance and Policy, Office of Manufacturing Quality, CDER, Office of Compliance, FDA.
• Bob Rhodes – Sr. Vice President, Quality & Compliance Services, Quintiles