Prioritization of Nonclinical Data
Prioritization of Nonclinical Data
The Standards Roadmap Team created a survey for members of industry to understand the priorities of the many stakeholders of nonclinical data. We asked them to consider the entire expanse of nonclinical studies listed for Module 4 of the eCTD. Responders rated the study types with a scale of high, medium, or low priority or had the option of leaving it blank (indicative of no preference). A spot to comment on rationale for the preference was provided. Finally, responders were asked to indicate whether they were responding as an individual or on behalf of their organization. Results Respondents consisted of both companies/institutions (n=4) and individuals (n=11) throughout industry. Overall, there was no significant difference between company and individual respondents.
The results of the survey indicated that Carcinogenicity and General Toxicology were the highest priority study groups (Figure 1). This was not surprising and supports previous decisions by the SEND team to standardize these first. Developmental and Reproductive Toxicology (DART) and Safety Pharmacology were rated the next highest priorities. Indeed, standards for these two study groups are currently being developed. Pharmacokinetics studies were considered to be a medium priority, along with Genetic Toxicology studies. Respondents differed on the utility of pharmacology studies, which received both high and low priority status, hence it is labeled as lower priority in Figure 1.
The Roadmap team recognized value in keeping study types grouped since conventions of standardization may be applied to several study types within a study grouping. Study types for developmental and reproductive toxicity (DART studies: Segment I, II, III) were similar in their perceived high priority. Safety Pharmacology had both high and low priorities among their study types (Figure 2A). Note that Respiratory and Cardiovascular Safety Pharmacology study types received the highest priority and are presently being standardized. CNS Safety Pharmacology also rank high, while Renal, Autonomic Nervous System and Gastro-Intestinal systems are lower. Pharmacokinetic and Genetic Toxicity study groups received high/medium scores across their respective study types.
Figure 2B captures prioritization of miscellaneous studies. Immunotoxicity and Receptor Screens were ranked highest, while all other studies take medium to lower importance.
A prioritization of several data elements which can be applied across study types is also provided in Figure 3. Respondents considered creating standards for Historical Control data, Study Design/Logistics, and Clinical Signs of highest importance. Formulation Data, Biomarker Incorporation, and Metadata content also were important for standard implementation.
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Overall, Carcinogenicity, General Toxicology, DART, and Safety Pharmacology were ranked highest among study groups for creating standards. Work is already in progress for standard creation in each of these study groups. Additional study types that are high priority for standards development include CNS Safety Pharmacology, Pharmacokinetics, Metabolism, and Bacterial Reverse Mutation Assays. Further, there is a desire for historical control data, study design, clinical signs, formulation data, biomarkers, and metadata to be standardized sooner rather than later. These will be more challenging and difficult to implement.