As clinical operations specialists, we have the responsibility to execute clinical programs in a way that offers the highest probability of success. We lead the cutting edge of the clinical development process and our role is to synthesize scientific, business, regulatory, and global project management needs into a coherent path forward.
If we are doing our jobs properly, this should yield the best possible results – compliance to GCP, timeliness, and scientific and business content that are of the highest caliber. As we are all too aware, clinical studies are an inherently risky proposition and a failed study can negatively impact a company’s valuation as well as wasting irrecoverable time and resources.
So what kind of crystal ball do we use to look into the future? Instinct, metrics and performance to milestones should give us a pretty good idea of how well a program is planned and executed. As the program heads down the path toward regulatory approval, enrollment, and beyond, we sometimes encounter warning signs that the project won’t likely succeed or will need a major reset to have any chance of success. Here, I would like to propose 10 warning signals for consideration:
1) Poorly Chosen Scientific Endpoints
Of any item on this list, an incorrect choice of scientific endpoint is the most insurmountable. No amount of post hoc analysis can correct for it. When a careful analysis of preclinical and early stage clinical results is not done, or when the scientific rationale for a study isn’t well considered, successful results are unlikely to come your way.
2) Poorly Developed Protocol
Even a study with brilliantly conceived endpoints can fail if the protocol is not well thought out in terms of practical elements, such as execution, device deployment, and GCP compliance. Sometimes a protocol can be “over-engineered” without consideration of coordinator time or skill level requirements of other project associates. It may also be that the device you are testing requires a lot of expert advisor/application support in the operating room, and these resources simply do not exist at your clinical sites.
3) Improper Planning and Staffing
In smaller biotech firms, there may be naivety about what is involved to implement even a straightforward drug or device study. Is there enough critical mass to move the study forward? Sometimes management-rich clinical departments don’t budget the appropriate day-to-day resources essential to clinical trial execution. This can translate to poor timeline performance and a lack of translation between the scientific and practical elements required for study implementation.
4) Overuse of Consultants
There is no shortage of expert clinical research consultants, therapeutic key opinion leader consultants, and other subject area experts. Without question they are often superb and valuable resources. However, they may not have the focus, access to in-depth sponsor information, or the overall desire to ensure that a thorough and complete analysis of the project is done. Consultants will do a good job of understanding and advising you on how to proceed, but the sponsor shouldn’t always take any advice at face value.
5) Unrealistic Timelines/Rush to get to FPI
Often, we face steep timelines and a myriad of interrelated tasks. This can be challenging. Clinical research has many moving parts, some less obvious than others. When a study has been scheduled for implementation, a lack of appreciation for these moving parts can lead to unrealistic timeline performance milestones. In situations like these, corners are cut and overall quality of the plan may be sacrificed. One common example is when protocol development time is excessive and the time needed for proper planning and execution is rushed.
6) Top-downward Management
Input from field staff is essential during the tactical stages of planning. If a team wise approach to clinical operations is not observed, there can be a lack of alignment, leading to a situation where the field simply cannot accomplish the impossible, case in point, poor enrollment due to unrealistic enrollment criteria.
7) Command Failure
A clinical project can be thought of in military terms because of the similarity between launching a campaign and that of executing a study. Detailed research, a thorough understanding of the situation and terrain, attention to detail, and clear planning will lead to well executed studies. When the focus wanders, good results are not likely to follow. A well-led clinical development program that utilizes team planning has the greatest likelihood of success.
8) Under-resourced Device Implementation in the Operating Room
Some trials may involve numerous external specialty CROs, partners, device proctors, etc. Failing to understand the complexity of these requirements can have extremely serious consequences. Take care to completely understand this issue and resource appropriately.
9) Going into a pivotal study with insufficient data
Among smaller drug and device companies, there is the hope of “one and done” in terms of the studies needed to obtain either an approval and/or to generate compelling data to attract a buy-out. This can bea short-term solutiondriven by financial constraints. Sometimes a longer approach will lead to better chances of success.
10) Unrealistic Operational Elements
And finally, ALWAYS check and check again for unrealistic elements within your protocol. Eliminate anything that can cause expensive or negative consequences, eliminatecostly “want to have” items; these can hinder enrollment, create massive cost overruns, and demotivate your research team.
Summary: A well thought out, well-organized and well-executed approach offers the greatest chances of scientific and operational success.