During the clinical development of pharmaceuticals, it is not uncommon for a program to end prior to licensing agreement or commercialization. From regulatory filings and clinical development plans; chemistry, manufacturing, and controls (CMC) and quality management; preclinical and clinical results; the reimbursement landscape; and the competitive landscape, successfully conquering the dynamic terrain requires an equally dynamic approach. Regardless of the stage of product development or functions for which you are responsible, setbacks and failures will occur, whether it is ambiguous data, rejected batches, stability issues, or a global pandemic.
But biotech companies can avoid some of these common pitfalls during the clinical trial phase of drug development through dynamic and humble management techniques.
Hiding Behind PowerPoint: The Under-Developed Plan
Presentations are an effective tool to guide audiences while information sharing. Clinical development slides are often presented to external stakeholders to obtain funding. These presentations are a static, a point-in-time snippet of information. Nevertheless, many companies and individuals mistake these presentations for a comprehensive, dynamic, and integrated drug development plan.
Clinical development is truly an applied science. Unlike a series of PowerPoint slides, the path to commercialization is seldom a linear process and never simple. For example, what if the regulatory agency doesn’t agree with the pharm tox plan? What are the downstream impacts of changing manufacturers or manufacturing methods? An integrated clinical development plan (CDP) should have contingency plans and risk-mitigation strategies in place.
Setbacks should not be the first time the CDP is revisited. While no one wants to “waste time” updating an internal document, CDPs should be reviewed and updated on a regular basis as it:
- Acts as a consensus builder
- Serves as the primary location to track and manage key planning data
- Unearths unexpected expertise from team members
- Offers a rallying point when failures occur—to recalibrate and see a future ahead
Another common mistake or missed opportunity is making presentations to regulatory agencies for the sole purpose of documenting a hypothetical business plan. The communication should be complete, non-fictional storytelling, informing the regulatory agency of the plans to comply with their requirements, whether by generating new data or providing existing data to support your strategy. This can provide an opportunity to obtain true guidance and feedback from the regulatory agency. The regulatory presentations help to define the path forward, but do not illustrate how to proceed, or what activities can be activated on parallel tracks. While you may share enough information to get them to clear the Investigational New Drug Application (IND) or advance clinical studies, you will not be informed that there are more efficient ways to develop your technology.
A common pitfall is a hyper focus on short-term goals at the expense of the long-term health of the clinical development of a product. For example, you may have decisions to make related to spending on nonclinical verses clinical activities. Clinical spending looks much sexier than nonclinical spending, particularly when presented to external stakeholders or in a press release. However, jumping ahead of necessary nonclinical activities may later hinder your program.
This can result in a cognitive bias during clinical development, explaining away results that deviate from plans or stopping a clinical program to obtain more nonclinical data. In this scenario, attempting to keep a program alive comes at a cost, and narrowly positioning information is a perilous path for development.
Myopia can occur when focusing only on selling an asset or company as soon as it hits a specific stage. While it is possible to successfully sell off a product or company without performing all necessary nonclinical or early-stage clinical work, it will likely be at a lower valuation and may burn bridges for future deals.
There is a battle between positive and negative news. Positive news and positive data generate revenue, which is used to generate more data, which advances the program. However, negative news due to poor decision-making is insidious and can infect not only the present program but also the future development of the technology.
Another way of practicing myopia in clinical development is by not investing adequate time or resources in key infrastructure relevant to the current and near-term development phase. Often, vendors are selected based on personal history and/or their willingness to provide services within the company’s parameters. Documented processes, audits, and formal supplier qualifications are pursued only when problems arise, or when requested by external stakeholders. It’s important to have documented processes and a thoroughly negotiated Quality Agreement with your suppliers. Plus, defending your decision-making to third-parties is easier when they are documented along the way.
Another common mistake is under-communicating under the guise of reduced bureaucracy. Leaders who insist that “failure is not an option” cloud the ability to see the early harbingers of failure. Staff may not share directionally negative news, not wanting to be the person or the department that impedes the program. Avoiding or delaying information limits the company’s ability to make the adjustments needed to keep their development plan on-budget and on-schedule. Communicating in a balanced, healthy way is an art; great leaders know their own formulas for successful communication and there is no one-size-fits all approach. Practice is essential and, like much of clinical development, requires recalibration to adapt to changes such as corporate growth and the product development stages.
One simple way to encourage communication across an organization is to adopt a Fail Forward mindset, which implies that issues will arise and that everyone is responsible to call them out and suggest solutions. Some ways companies encourage a Fail Forward mindset include:
- Conduct regular internal and cross-functional meetings
- Use AI to predict target activity
- Acknowledge the need of redundancy and/or internal contingency planning
- Revisit the CPDs to ensure the decisions and actions remain consistent with your goals.
Under-communicating can also extend to regulatory agencies. The most important goal is to obtain guidance and feedback from the regulatory agency to ensure the most robust clinical development program possible. Whenever possible, ensure CMC, non-clinical, and clinical activities are congruent with the expectations of the regulatory agency. Deferring key discussions may delay product approval or jeopardize targeted label and reimbursement efforts. Additionally, the process adds significant value to external stakeholders who are looking to invest in your product, buy your product, or purchase your company.
Many tools and technologies are available that can and should be utilized to create state-of-the-art clinical studies and products. Nevertheless, simple, data-driven management that promotes effective planning, a strong balance of short- and long-term goals, and transparent communication can build effective leadership teams, companies, and healthcare products. These strategies are necessary to lead a healthy clinical development program to success.