Expanded Evaluation Guidelines for Certain Types of Trials:

Although the NCTN-CCSC gives highest priority to validation studies, exceptions may be made. NCTN and legacy Group clinical trial biospecimens MAY be considered available for use for broad exploratory/discovery studies (such as, but not limited to, unsupervised discovery of molecularly defined disease subtypes) under certain circumstances. The following conditions will be viewed as supportive (not necessarily definitive) for these uses, and the review of the proposal will occur within the usual framework of oversight by the NCTN-CCSC:

• The clinical trial involved a rare cancer, as defined by ≤3-6/100,000 new cases per year, and had a negative result.
• There are fewer than 50% of the biospecimens remaining from the clinical trial.
• The clinical trial was a phase 3 randomized trial that had a negative primary endpoint outcome and was published >5 years previously.
• The clinical trial was a phase 3 randomized trial published ≤5 years ago that had a negative primary endpoint outcome, and for which the experimental agent is no longer under active investigation in this or a different setting.
• The proposal does not consume specimen (such as a slide imaging study) and the specimens used will be returned unaltered to the Bank. If the digitization has not already been conducted, the proposal will be reviewed by the NCTN-CCSC. If the digitization has already been conducted, the proposal should be completed on the NCTN-CCSC Proposal Submission Form and submitted via PIO for review by the NCI Protocol Review Committee, not the NCTN-CCSC.
• Note: If specimens are requested from a Network Group biobanking protocol and have no association to treatment trials, exploratory studies may be considered. (These proposals would be reviewed by the NCI Protocol Review Committee, not the NCTN-CCSC. Also, there are other situations in which the review is not done by the CCSC – e.g., NCI Clinical Trials Sequencing Project; Expedited Review, Collaborative Trials with Outside Organizations with Steering Committees that oversee handling of biospecimens, small single arm phase 1 and phase 2 trials.)

Examples of proposed exploratory/discovery studies making use of biospecimen collections conforming to the scenarios above could include, but are not limited to:

• Purely exploratory analyses aiming to discover novel biological subgroups irrespective of clinical outcomes;
• High-throughput screening of very large numbers of molecular characteristics, individually or in combination, for their association with clinical outcomes or other clinical or pathological phenotypes (e.g., identification of lists of genes having expression level that correlates with survival or disease phenotype, or building a predictor of clinical outcome or adverse event with no strong a priori biological or mechanistic hypotheses).
• Such studies must have appropriate statistical plans to demonstrate adequacy of the proposed sample size (e.g., statistical power or precision calculations) and to demonstrate that statistical techniques will be employed to avoid generation of spurious results (e.g., false discovery control) and to identify and avoid overfitting of complex models (e.g., internal and external model validation).