BioMed Research International / 2013 / Article / Tab 2

Research Article

Practical Guidance for Implementing Predictive Biomarkers into Early Phase Clinical Studies

Table 2

Predictive biomarker checklist.

Team formation
Form team; include representatives from assay development, clinical therapeutic area, program management, regulatory affairs and clinical statistics
Establish regular team meetings
Sample collection considerations
Determine source tissue for biomarker analysis
Minimize amount of specimen required; use non-invasive techniques if possible
Allow 1–3 months if sample collection method does not exist
Train personnel at clinical site, if needed; create visual aids for training
Retain extra specimens for potential bridging studies
If utilizing a bridging strategy, initiate sample stability studies
If using FFPE specimens, establish minimum percent tumor specification
Select clinical sites with licensed pathologist able to mark slides and perform macrodissection
Collect extra sections before and after sections being analyzed for H&E staining
Perform sample collection experiment to qualify each clinical site, if necessary
Assay considerations
Clearly define and document assay intended use, how positive and negative calls are made and how results determine patient eligibility
Select assay technology platform, consider assay output, establish clear requirements
Develop validation strategy, validating each sample type or collection method
Allow several months to complete vendor agreement
Allow time for vendor qualification, if new vendor
Obtain clinical specimens for analytical validation and decision-point threshold
Allow 1–6 months for assay development for a CTA; at least 24 months for a IVD
Sample analysis considerations
Document anticipated turn around time from patients’ perspective
Document sample logistics from acquisition to patient test report
Request hour-by-hour workflow of assay from vendor
Have clinical site send specimen directly to testing lab if possible
Ask vendor to accept Saturday shipments, to work weekends or to work longer days
Avoid the use of local labs
Reduce cost by batching samples, for example, biweekly sample analysis
Explore alternate control strategies to reduce cost of running process controls
Consider performing assays sequentially if using multiple predictive markers
Calculate and document anticipated screen failure rate
Regulatory considerations
Identify CLIA lab with appropriate state licenses or allow 1–6 months for lab to obtain necessary licenses
Discuss high complexity assays with FDA before implementing in clinical trials
Set up pre-submission meeting with FDA in advance of clinical trial
For companion diagnostic development, work closely with partner on timelines

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