CLINICAL OPERATIONS


likely be salary and wages of staff involved in conducting study oversight and other critical study activities. However, with the dose- escalation recruitment timeline almost doubling, a well-written risk management plan should consider the additional internal costs incurred, resource allocation consequences and opportunity cost. For example, while these employees are dedicating additional time and resource to this study, other current or potential future studies may be negatively impacted. The small and emerging biotech should ensure an adequate contingency of human and financial capital has been identified and allocated to the project to cover additional unplanned costs. Consideration should also be given to whether the stability and shelf-life characteristics of the study drug lend themselves to such a significant extension of the study timelines. Note that the timelines presented above only concern enrolment of subjects, and not the length of potential therapy. Should the stability and shelf-life study be ongoing, then consideration could be turned to potentially extending the number of data points (assuming that sufficient material has been reserved and is available for stability and shelf-life studies) to extend the expiry date of the study drug. As a guiding principle, the small and emerging biotech should conduct stability and shelf-life studies, which are at least the length of its proposed study, using a ‘conservative-case’ scenario to potentially mitigate the hypothesised scenario. These might include slower than anticipated recruitment, sluggish site activation, subject drop-outs, screen failures, increased DLT observations, etc.


If the stability and shelf-life study cannot be extended, or the current data supports a finding


“Consideration should be given to whether the stability and shelf-life characteristics of the study drug lend themselves to such a significant extension of the study timelines. Note that the timelines only concern enrolment of subjects and not the length of potential therapy”


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that the study drug is unstable beyond the current expiry date, then further manufacturing batches are likely to be required. This could result in a recruitment hold until manufacturing is complete, therefore jeopardising the completion of the study. However, conducting additional manufacturing isn’t as easy as flipping a switch. The most critical component (besides adequate funding) will be the availability of your contract and development manufacturing organisation (CDMO) partner having sufficient capacity to conduct further manufacturing. Where possible, the small and emerging biotech could consider booking additional production slots upfront, especially if it is able to negotiate reasonable cancellation terms or, alternatively, utilise those production slots for another product or a later phase study, as a risk mitigation tool. Corporate timelines are also likely to significantly influence the risk mitigation activities undertaken by the small and emerging biotech. Should preliminary clinical data be required for a major corporate or commercial event (for example to conduct a further fundraising round to meet a milestone of a previous round [ie a further tranche of a committed investment] etc), then the timeline extension presented between the two scenarios above may raise a chicken-and-egg situation. As such, additional funding may need to be allocated to complete the study – however it may not be possible to raise the additional funding without the data from the study. While the clinical operations professional may be able to influence and provide input to corporate events (as they relate to clinical development), the scenario presented above demonstrates the requirement to provide not only best-case scenarios, but to also explore a number of conservative analyses of less-than-ideal scenarios.


Summary Clinical development for the small and emerging biotech is frequently a trade-off between certainty and uncertainty, and between over- planning and under-planning. While it is unrealistic to aspire to perfection, and unacceptable to aspire to less, the small and emerging biotech must appreciate the nuance of clinical study design and how different circumstances can have such drastic time and cost implications to the project.


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