6 Common (But Easily Avoided) Risks Observed In Clinical Research
April 20, 2018
Analysts report that more than 90% of all drug candidates entering the pipeline fail to make it to FDA approval and commercialization. If categorized by phase, a higher failure rate is understandable in early phase, exploratory trials such as Phase II trials that see a failure rate of approximately 70%. But what is surprising is that even Phase III trials that are much further along in the discovery process report failure rates of nearly 50%. Compound that with the fact that more than 30% trials are often significantly delayed, and that the high rates of failures and delays not only takes a huge financial toll but also results in wastage of precious time and effort on the part of sponsors, sites, researchers and patients; and you have a domain that begs a closer look at the reasons that so many trials fail or are delayed and what, if anything, can be done to improve the process.
Widely known reasons for failure are issues with efficacy and safety, and failure to demonstrate value compared to existing therapies. And while these are all critical issues, often the reason for failure or delay is not due to one of these reasons that is an inherent part of the scientific discovery process but rather due to problems with process management, missed deadlines, lack of clarity and mis-communications – many of which are avoidable if managed correctly from the initial stages. Listed below are some of the risks that can be avoided through detailed planning, effective management and efficient oversight of a clinical research program.
1. Starting your research with a protocol that is not fully developed or lacks details causing ambiguity in the process
This may seem to be an obvious point to most readers, but often trials resulting in failure or delay have missed incorporating key elements or have not clarified them adequately. It is important to start the process with a detailed, clearly written, and fully thought out protocol since this becomes your foundation for all subsequent steps. Having an experienced peer group review and critique the protocol further strengthens the base for your research through helpful input and suggestions.
2. Failure to develop a detailed project plan leading to missed deadlines
Another commonly observed problem in clinical research is not being able to meet required criteria and timelines specified by regulatory, institutional and other agencies. While research teams are typically aware of common milestones such as IRB approval, database lockdown, and FDA submission etc., there are many other tasks that they may not be aware of or have failed to include in their project plan thereby not accounting for them when estimating resource effort and timelines. This can include trial-specific reviews, special trainings, need for specific documentation and communication, among others. It is therefore important that all steps required for the entire project are outlined upfront and a detailed timeline created to keep all tasks on track. Once again, getting peer input for this process is very helpful. Also, do not forget to share this plan and timeline with all appropriate members of your team so that everyone is on the same page!
3. Difficulty in finding appropriate sites/researchers leading to delayed activation and overall prolonged timelines
Although this is one of the most critical and rate-limiting steps, the process of identifying appropriate sites and investigators to participate in a study often begins later in the cycle than it should. Without having sites on board, the study’s conduct phase cannot be initiated. And without having the adequate number of sites on board, reaching the protocol’s specified accrual sample size in a timely manner is in danger. Although most protocols include a plan for how sites will be trained and initiated (after they have been recruited), they often forget to think through the details around how they will go about identifying appropriate sites and contingencies that they should plan for if they face challenges on this front.
4. Failure to recruit according to the protocol’s recruitment plan leading to delayed trail completion
Subject recruitment is a complex topic with multiple factors that can have an impact on the overall recruitment effort. Among the multiple risks is one that can be easily managed through upfront meticulous planning that helps in making this a more streamlined process. In addition to being clear about the inclusion and exclusion criteria in the protocol, it is important to make sure you have a written recruitment plan that will be followed during the study. Be sure to include elements pertaining to subject engagement and retention, and for an oversight program that ensures constant monitoring of your recruitment efforts.
5. Shortcomings in the informed consent process that can have severe downstream consequences
Staff members involved in the screening and enrollment process are trained to understand the value of following a compliant informed consent process for each subject being recruited for a study. However, it is surprising that there is still a great deal of variability in how complete and thorough this understanding can be. Issues can arise if subjects do not properly understand what they are signing up, if the consent captured is incomplete or performed at an incorrect time, and other such deviations that can be avoided by maintaining fully trained staff and a compliant program.
6. Inconsistencies in clinical research data capture and not addressing the errors in a timely manner leading to delays or rejection
The final stage in determining the success of a trial is dependent on the data collected during the process and therefore it is a critical output that must be clean, accurate and evidence-based. This means that the process to capture data must be well managed, data cleaning should occur in a timely manner, and all source documentation must be available for verification. Electronic systems have certainly helped improve the overall data capture process, but due consideration must also be given to critical related aspects such as data integrity, monitoring and analysis.