Not surprisingly, the majority of nonclinical contract research organizations are not in glamorous locations. So arriving at the front door of one at 7:30 on a snowy or rainy morning isn’t likely on anyone’s bucket list. However, the experienced nonclinical scientist understands that no matter the duration, scope, or objectives of a study, monitoring visits are a critical part of any nonclinical (or preclinical) program. A monitoring visit is the opportunity to see your study, observe how the study director manages activities, assess the ability of the technical staff, and review overall adherence to the study plan.

Nonclinical study preparation

Each nonclinical study is a series of critical decisions that the nonclinical scientist monitors and oversees for every program. While highly critical, the in-life initiation of a study is simply the next step in the process of the program. Before study initiation, nonclinical study preparation includes determining the study objectives, designing the outline of the study, selecting a CRO with the necessary expertise and experience to complete the study (or at least the CRO with the most suitable timelines), and, of course, reviewing and approving the specific study plan.

From the comfort of an office, the nonclinical scientist will have spent the preceding days, weeks, and months engaged in multiple discussions with the study director around the study plan and the test item, with its expected pharmacology and toxicology. The dose formulation preparations and schedule of events will have been reviewed, with time-critical events identified.

As the monitoring visit gets closer, the nonclinical scientist will have reviewed the specific tasks that were appropriate for the day. The dose formulation instructions will have been provided and reviewed, ensuring that the proposed dose volumes are suitable based on the route of administration, dose volume, and animal species. Sampling schedules will have been reviewed, with preparations made to have the samples shipped to the appropriate labs for analysis.

Nonclinical study initiation

Back to that cold, snowy Montreal morning, when the nonclinical scientist is pulling on extremely comfortable shoes in anticipation of hours spent on site. Prior to arriving at the CRO, he or she will already have spent hours thinking through the study: how it was designed, the objective, the scope, the complexity — and always, how it could all go wrong. All of the possibilities for error and mistakes will have been considered and reviewed with the study director to ensure that steps are put in place to prevent their occurrence, or at least reduce their impact.

However, the experienced nonclinical scientist also knows that biology can be messy, imperfect, and susceptible to setbacks. It is for this reason that a monitoring visit must occur. It is never possible to anticipate how or what or why or when, but every study is susceptible to error and failure. The study monitoring visit is the best opportunity to observe, identify, respond to, and mitigate the unexpected problems that could derail the study.

Consequently, the nonclinical scientist will be prepared for the day, physically and scientifically. The study plan will have been read and reread, relevant sections highlighted, and critical issues circled in red. Copies of the study memos, formulation preparation, necropsy schedule, and daily events will be available, and the nonclinical scientist will have reviewed facility SOPs to have an appreciation of how technical staff will work. Finally, the nonclinical scientist will have an understanding of the investigational product and be aware of any unique potential issues that could arise due to the pharmacology or toxicology of the drug.

However, even in a simple study, there will be many activities that must occur simultaneously, making it impossible to review everything. Therefore, the nonclinical scientist must decide in advance those critical aspects that must be monitored, just those critical tasks that can make or break a study. Ideally this is where the nonclinical scientist’s experience will be evident, not only in understanding the new therapy and expected effects, but also in ensuring that the activities are being performed in accordance within the study plan and SOPs. Premier Consulting is deeply familiar with the CROs where it places studies, and that familiarity allows its scientists to make knowledgeable and informed decisions when preparing for and monitoring each study.

With all this preparation complete, the nonclinical scientist can complete the visit.

Nonclinical study monitoring report

The visit is followed by a monitoring report that summarizes of the visit to the CRO and lists study-critical activities that were monitored, be they Day 1 dosing, terminal activities, or data review. Occasionally, the report is a critical review of the problems and issues encountered during the visit and how they were resolved. More often, if the nonclinical scientist prepared correctly, the report is a detailed, comprehensive, and entirely predictable summary of a successful study. In either event, all members of the nonclinical development team can sleep a little easier, with greater confidence that the study is continuing and the development of the drug is proceeding.

Premier Consulting offers a full-service solution to support nonclinical study design, CRO selection, and on-site monitoring. Contact us to learn more.

Author:

Andrew Emanuel
Senior Project Director
Premier Partners