Navigating the landscape of vital drug development? Discover the five crucial areas that could make or break your success.
Early-stage drug development encompasses the initial phases of researching, testing, optimizing, and evaluating new therapeutic treatments in early-phase clinical trials.
The high-risk, high-reward nature of early-stage drug development compels stakeholders to seek and capitalize on every opportunity to enhance the chances of success. ProPharma's experience serving clients in this sector has enabled us to identify five, relatively common yet often overlooked development program "blind spots": Organizational Misalignment, Inadequate Planning, Arbitrary Decision-making, Incomplete, and insufficient Risk Management. Addressing these shortcomings proactively through effective leadership and expert program management significantly enhances the likelihood of success in early-stage drug development.
1. Organizational Misalignment
Organizational alignment improves the team's capacity to make high-quality decisions quickly by ensuring that every stakeholder across the organization, regardless of their position, possesses a clear understanding of program strategy, objectives, and constraints. This, in turn, enhances both decision-making and implementation. Organizational alignment may be especially beneficial during preclinical and first-in-human clinical development lifecycle stages, when there are significant constraints on timelines, budgets and critical expertise where scientific and regulatory uncertainty is at its highest.
Proactive Program Management invests the time and resources necessary to develop and maintain effective and constructive communication amongst the impacted functions. Despite its apparent simplicity, this remains an area of consistent neglect due to the diverse priorities of each key stakeholder group. The program manager provides the essential function of driving organizational alignment by purposefully and continuously integrating organizational alignment with deployment of project status, risk management activities, task prioritization, and communication tools.
2. Inadequate Planning
In Early-Stage Drug Development, the primary focus is on remaining research, candidate optimization, and early trial design and execution activities. While there's agreement that some level of agility is necessary for success during this stage, we've observed that excessive agility often sacrifices efficient execution and proactive issue identification due to a lack of structured planning.
Charging ahead at full speed without a well-defined project plan, schedule, and governance process is a common shortfall of early-stage drug development programs. Often, leadership tries to comprehend and manage this complex program through a collection of functionally siloed "plans" of varying formats such as Excel, PowerPoint, Smartsheets, MS Project, or conveyed verbally. These plans are typically created and 'owned' by functionally accountable SMEs and senior leaders, often without established standards for timely, meaningful, and systematic updates. This approach heightens the risk of overlooking, concealing, or rendering critical program information difficult to comprehend. The typical outcomes are missed milestones, unidentified dependencies, cost overruns, emergency leadership meetings to course correct, and last-minute changes in execution strategy, thereby delaying important decisions and negatively impacting quality, cost, and timeline.
Effective program management dedicates the time and resources needed to develop and maintain a comprehensive, cross-functional, integrated, value-added project plan. This plan offers a realistic representation of each workstream through a single, visible, technological solution, accessible to all stakeholders involved. The Program Manager drives this approach by proactively engaging Program leadership and functional SMEs in an easy-to-understand, flexible and on-going governance process and the deployment of situationally appropriate project management tools to capture timelines, resources, scope and systematically refining them through cross-functional collaboration.
3. Arbitrary Decision-making
Commonly observed in less mature early-stage drug development is the design and execution of a process or analytical development protocol without rigorously establishing objective, cross-functionally agreed-upon acceptance criteria. Common misconceptions underpinning this occurrence include the belief that the lack-of-knowledge, "small" sample sizes and Program timeline constraints make use of "I'll know it when I see it" acceptance criteria preferable to creating objective acceptance criteria.
Conversely, the cost and time constraints in early-stage drug development emphasize the importance of rigorously adhering to the scientific method, which involves setting objective acceptance or rejection criteria. Mature programs that prioritize the establishment of objective acceptance criteria create room for thoughtful discussions on experimental design, including considerations of objectives, cost, and complexity before execution. This approach also enhances the value of post-execution work, such as recognizing and preventing non-value-added tasks, by maintaining a focus on objective criteria Time invested in objective decision-making likely has the added benefits of dampening the impulse of some to make last-minute, under-the-radar experimental design changes (which can greatly diminish experimental power) and fostering the forward-looking paradigm that all development program activities must fit together to create the knowledge needed for success, e.g., creating objective criteria for technology transfer.
Effective Program Management invests the time and resources necessary to develop and maintain an objective decision-making governance process. The Program Manager drives this approach by engaging Program leadership and functional SMEs in an easy-to-understand, flexible and on-going governance process. They also deploy situationally appropriate project management tools to assure that an objective decision-making process is followed.
4. Incomplete Analysis
Generating the required process and analytical data necessary to drive early-stage development takes a major investment of precious program time and money. With the pressure to move quickly, the analyses of partial datasets typically do not result in robust outcomes; it potentially undermines downstream activities and viability of future investment by funding entities. The problem is usually rooted in an inadequate system of governance characterized by contradictory, confusing and variable norms and infrastructure for data generation, capture/access and analysis. This erects formidable barriers to effective team collaboration on this critical, ongoing program imperative. "Talk-through" analysis, where one or two credible experts verbally discuss hypothesis and provide "conclusions" in a single meeting, frequently prevails as the predominant form of analysis in this setting. This analysis technique is biased toward the notion of the leader(s), glosses over historically relevant data, underplays the expertise of multiple functional area SMEs, and is very difficult to document objectively. The harmful effects of these erroneous conclusions are amplified as they cascade forward as the basis for the next data collection protocol.
Effective Program Management invests the time and resources necessary to be agile, develop and maintain a comprehensive, value-added data generation, capture/access and analysis governance process. Program Managers drive this approach by engaging Program leadership and functional SMEs in an easy-to-understand, flexible and on-going governance process and by deploying situationally appropriate project management tools to assure that data generation, capture/access and analysis processes are followed.
5. Insufficient Risk Management
A broad consensus, as evident in regulatory and professional literature (e.g., ICHQ9 and PDA) underscores the integral role of formal Quality Risk Management (QRM) in early-stage drug development. This comprehensive approach encompasses risk identification, ranking, mitigation, acceptance, and communication. And yet, having no clearly defined process to manage quality risk remains a common shortfall of early-stage drug development programs, usually grounded in an underappreciation of the power of QRM to focus attention on the highest risks, drive objective decision-making, prevent or substantially mitigate the impact of failures and to unite Program efforts around acceptable level of acceptable risk tolerance per the company's definition. A properly implemented and managed QRM process facilitates the realization of these benefits within a rapid decision-making environment, reducing program delays and cost overruns, and even preventing outright
Effective Program Management commits the necessary time and resources to establish, apply and sustain the QRM process right from the program's inception. This approach extends QRM principles to scientific and regulatory activities under workstreams for:
- Non-GMP & GMP drug product manufacturing and analytical development
- Technology transfer
- Preclinical Proof of Concept and Toxicology
- First-in-Human clinical study.
The Program Manager drives this approach by engaging Program leadership, QRM Process Owner/SME(s), and cross-functional SMEs as part of the project team's existing governance process. The combination of QRM tools and the team's proactive integration of QRM into their execution process should enhance the execution and realize the benefits of the early-stage drug development program.
Conclusion
Early-stage drug development is the cornerstone upon which patient well-being and the aspirations of investors thrive. Program managers must extend their efforts beyond mere scheduling, recording minutes and action items, and prioritizing tasks based on the ad-hoc preferences of individuals. They should concentrate on employing advanced tools and techniques for the effective execution of a structured, early-stage drug development Program. Proactive program managers who address the five identified programmatic shortcomings significantly boost the likelihood of success in early-stage drug development. They should actively involve leadership and functional SMEs in an ongoing governance process that is easy to understand and flexible, while also using project management tools suited to the situation.
Ready to redefine your early-stage drug development strategy? Get in touch with ProPharma now, and let's start your journey.
