As I sat down to compose my next article for Animaf Pharm, I decided to reread some of my past articles for inspiration. I suddenly realized that I have been writing these articles for nearly five years. This prompted me to reflect on all of the topics I have addressed and I began to wonder whether things have changed in any significant way over the last half-decade.
In my very first article in July 2010, ‘Cutting Delay in Clinical Trials; I cited the shocking statistic that 90% of all clinical trials experience significant delay.
I then listed the four principal causes of study delay: slow subject enrollment; poor data quality; lax test article control; and weak project team communications. From my experience, I would say that these problems still exist, in one form or another, in most studies. However, I would now reclassify these causes of delay under two main categories: study planning and study execution.
So many study problems could be eliminated by better and more comprehensive planning, especially since there are a variety of project management systems that can track every step in the entire study process. Project teams that use one of these systems can more efficiently allocate their resources and avoid most last-minute ‘crunches’ and missed milestones.
Unfortunately, I still see protocols being revised right up to the night before the investigator training meeting. All too often , our project teams discover case report forms that have not been reconciled against the protocol’s data collection specifications and then tested for logic, consistency, and ease of completion.
This oversight increases the likelihood of high query volume , protocol deviations, and lost cases. In studies that employ electronic data capture, appropriate edit checks that could have been programed into the system to simplify data entry and reduce query volume have been left out.
All members of the project team should participate in the development of a comprehensive listing of all study tasks and an unambiguous assignment of those responsibilities to help prevent misunderstandings and missed deadlines. They also should agree on a communications plan that includes a schedule of regular project team teleconferences and clearly specifies what reports are to be delivered to whom, by whom, and when.
The old saying ‘plan your work and work your plan’ definitely applies to clinical trials. The best planning can be diluted by unorganized execution.
No trial can succeed without a team of dedicated investigators, each of whom should be evaluated and selected with great care. It is important to remember that, while every investigator may be a good veterinarian, every veterinarian may not be a good investigator.
Even years of experience as a clinical study investigator do not necessarily translate into top performance. Spending extra time to qualify each investigator and assess their level of interest in, commitment to, and understanding of the study will pay big dividends later on.
Study training is the next most important determinant of a successful trial. Regardless of which of the three training methods a sponsor chooses (group webinar, individual on-site, or centralized investigator meeting), training should be designed with different investigator learning styles in mind. Failure to do this could result in some investigators leaving training with an incomplete or inaccurate understanding of the protocol and other study requirements. Some form of testing should be included as well to identify areas needing additional instruction during site initiation visits.
Slow enrollment still seems to be the bane of many trials. Sometimes, the site has an insufficient patient population from which to recruit potential subjects. More diligent site qualification can minimize this situation.
Some investigators do not completely understand or misinterpret the inclusion / exclusion criteria, resulting in high screening failures but low enrollment. Proper training before the study starts, followed by close tracking of screening failures to identify the need for remedial training, can eliminate this problem. Some sites lose interest in the study, causing enrollment to drop or stop altogether. Again, thorough evaluation of potential investigators, paired with close monitor support, can keep enrollment on target.
Test article inventory control and reconciliation is another area requiring special attention. Confirmation that each site has a separate, secure storage area is an essential part of every site qualification visit. Dose counts should occur upon test article delivery and before and after every subject visit. A complete inventory reconciliation should be completed during each monitoring visit.
Such rigorous measures are critical for every study that is evaluating an unapproved product, and especially important for products that must comply with the US Drug Enforcement Administration’s regulations.
Of course, the ultimate goal of any clinical trial is a body of clean, complete, and accurate data that supports a regulatory decision regarding the new product. While progress has been made in recent years, some regulatory submissions are still derailed by defective or missing data that somehow eluded the study’s data reviewers. The phrase ‘attention to detail’ remains the mantra for everyone engaged in this activity. It is not an overstatement to say that the success or failure of each trial rests with them.
To use yet another old saying, the more things change, the more they stay the same. The business of clinical trials has evolved and improved over the last five years. The keys to success, though, remain unchanged.