Nand Kishore Rawat is a Director and Head, Early Phase Biostatistics based in the King of Prussia, PA Cytel office. We recently spoke with Nand for the Cytel podcast to gain his thoughts on the unique aspects of Phase 1 development and where innovative approaches supported by thorough planning can meet these challenges head-on. Read on for key insights or listen to the podcast.
A Candidate Product Reaches Phase 1
The introduction to Phase 1 clinical testing is a significant milestone for any candidate medicinal product. After several years of In-vivo safety pharmacology and toxicology studies, a multi-disciplinary team has evaluated all the data, and decided to invest in clinical development: from the laboratory to actual testing in humans.
The traditional development model leads to sizeable Phase I trial packages requiring multiple studies, each months long.
However, our conversation with Nand reveals that with thorough planning and flexibly-written protocols, many objectives can be addressed in a single protocol to streamline the acquisition of data that hopefully justifies continuance to Phase 2.
Key Development Planning Considerations
Nand Kishore Rawat recommends when planning such a multiple objective “combination study”, the sponsor ensures that all study aspects are clearly explained. For example, the stopping rules at the individual, cohort and study level, the maximum number of subjects and especially the dose selection decision rules must all be well defined.
Nand also advocates for instituting an appropriate data review process for each key decision stage and identifies these key consideration points for data review meetings:
Determine the required data to base decisions (PK, adverse events, lab results, etc.)
Build in sufficient time needed for sample analysis and data transfer
Account for time required by the Pharmacokineticist, statistician and other study team members to analyze and report
Dose escalation decisions are usually made jointly between the clinical development team and the investigators. To ensure the trial’s integrity, the decision participants must avoid revealing anything about the treatment blind with the investigator or other study personnel.
On Choosing and Retaining Phase 1 Trial Subjects Nand next emphasizes the importance of avoiding dropouts. He advocates for better communicating the Phase 1 trial’s exploratory purpose and the motivation to the healthy volunteer subjects especially. Withdrawals occur when the study is too complex and interferes with daily life. With their comparatively limited sample sizes, many Phase 1 studies risk of failure from even a handful of withdrawals.
It’s also important for sponsors to understand the consequence for protocol design complications. Sponsor do well to listen to the clinical site team – seek feedback on any procedures or tests that could place compliance at risk.
The Optimal Early Stage Development Partner Nand concludes with a discussion on the advantages of conducting Phase 1 trials with a data-driven expert provider. Cytel addresses Phase 1 challenges by helping sponsors and their stakeholders to achieve:
Alignment between data management, biostatistics, and statistical programming groups supports the efficient data analysis post-lock
Consistent data handling approach and analytical rules across studies reduces the sponsor’s oversight burden
Significant efficiencies gained from globally-based personnel (US, EU, India): shorter turnaround time, cost efficiencies (e.g. standalone PK/PD reports). It’s especially critical where there are at risk populations, or safety concerns in play, that any interim analyses can be produced within tight timelines
Access to pharmacokineticists and pharmacometricians with in-house licenses of Phoenix WinNonlin. Displays of PK concentration and parameter data across studies make for rapid study review
Adoption of standardized CDISC format for Phase 1 traceability, for future data pooling and subsequent submission
Click below and listen to the podcast.
Interested in our Phase 1 development services? Learn more about our Quantitative Pharmacology and Pharmacometrics pages and our Cytel Strategic Consulting pages or click here to arrange a discussion with one of our team.
About Nand Kishore Rawat
Nand Kishore Rawat, Ph.D. is a Director and Head, Early Phase Biostatistics at Cytel, with extensive statistical design and analysis knowledge to guide sponsors toward achieving their early Phase 1 development goals. In addition to his early phase statistics background, Nand is an active event organizer and regular contributor to Biostatistics, statistical programming, quantitative pharmacology and pharmacometrics conferences, including JSM, PhUSE, ASCPT and ACoP. Nand earned his PhD in Statistics from the University of Rajasthan. He is an adjunct faculty of statistics at Thomas Jefferson University in Philadelphia and Statistics.com. Prior to joining Cytel, Nand held statistics positions at Ranbaxy (now Sun Pharma), Novartis and Bristol-Myers Squibb.
Read Nand Kishore Rawat’s and our Pharmacometrics team members’ impressions of key topics at ASCPT 2017here.