EARLY-STAGE CLINICAL DEVELOPMENT
“The small and emerging biotech should ensure an adequate contingency has been identified to cover additional unplanned costs.”
considered or characterised in the risk-management plan. While this article is unable to reference all possible secondary implications, a number of key secondary implications are discussed below.
Secondary implications
A fully costed project budget would include overhead recovery (the largest component would 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 (while these employees are dedicating additional time and resource to this study, other current or potential future studies are 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 turned to whether the stability and shelf-life characteristics of the study drug lend themselves to such a significant extension of the study timelines, noting 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 a sufficient quantity of 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 that are at least the length of their proposed study, using a ‘conservative-case’ scenario (for instance, slower than anticipated recruitment, sluggish site activation, subject dropouts, screen failures, increased DLT observations, etc) to potentially mitigate the hypothesised scenario.
84 | Outsourcing in Clinical Trials Handbook If the stability and shelf-life study cannot be
extended or the current data supports a finding that the study drug is unstable beyond the current expiry date, further manufacturing batches are likely to be required, which could result in a recruitment hold until manufacturing is complete, jeopardising the conclusion of the study. Conducting additional manufacturing isn’t as easy as flipping a switch, however. The most critical component (besides adequate funding) will be the availability of your contract development and 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 they are 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 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 (to conduct a further fund- raising round, to meet a milestone of a previous fundraising round, etc), then the timeline extension presented between the two scenarios above may raise a ‘chicken and egg’ scenario. Additional funding may be required to be allocated to complete the study, although additional funding may not be able to be raised 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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