Ten Tips To Tremendous Trials #2 – A Continuing Series

Welcome to the second installment of my new series! The goal of each article in this series is to improve the quality of all clinical trials by reminding you, the reader, of another important step that will increase the likelihood that your next study will be completed on time, within budget, and with a minimum of complications.

Welcome to the second installment of my new series! The goal of each article in this series is to improve the quality of all clinical trials by reminding you, the reader, of another important step that will increase the likelihood that your next study will be completed on time, within budget, and with a minimum of complications.

That’s a lofty objective. But, since 90% of all clinical trials experience significant delays and a similarly hefty percentage suffer from mediocre data, ineligible subjects, or cost overruns, a return to basics is long overdue. Tip #1 focused on setting clear expectations for everyone involved before the study begins. Securing understanding of, and agreement on, key parameters up front ensures that everyone will be pulling their assigned load in the same direction.

Tip #2 explores another preparatory step: planning. Planning is one of those activities that most people understand, some actually do, and few execute with the level of detail and precision necessary to ensure successful execution. For me, the word “planning” always should be preceded by the adjective “comprehensive.”

In my younger days, I helped colleagues tape sheets of flip-chart paper around all four walls of a conference room as we created Gantt charts for our various projects. Today, there are many wonderful digital tools that simplify that effort and greatly enhance the planning process. One of the best is Microsoft Project. If you haven’t yet learned this program, it is definitely worth your time.

The beauty of such tools is that they display the entire life of a study, broken down into individual tasks, with start and end times for each. Tasks that must be completed in a certain sequence are readily apparent, as well as those for which order or timing is more flexible. Resources can be assigned to each task, which typically highlights segments of under- or over-staffing. This information enables the project manager to reassign tasks and resources to balance the work load throughout the study while maintaining the critical timeline from start to finish. However, whether you plan your trial using analog or digital tools, the discipline they enforce will minimize the tasks that you overlook and limit surprises once your study is underway.

Let’s consider several of the other important steps that often don’t get the detailed attention they deserve.

Protocol Writing

At the risk of stating the obvious, protocol development is the most important step in any clinical trial. It determines the activities to be performed by the investigators, the laboratory tests to be completed, the types and characteristics of subjects to be enrolled, the number and content of subject visits, and the specific data to be collected. Yet many trials rush to initiate study sites and begin enrolling before all aspects of the protocol and study design have been thoroughly checked and tested. Post-initiation amendments confuse investigators, complicate data review, and increase the likelihood of protocol deviations and unusable cases. Just as an incomplete recipe will not produce the finished dish you expected, so will a hastily-published protocol result in less-than-optimal data.

Site selection

Every investigator may be a good veterinarian, but not every veterinarian will be a good investigator. Therefore, it is essential that you define the characteristics of the ideal investigator and then evaluate each potential candidate against those criteria. Previous trials experience may be valuable if not offset by bad habits, sloppy data, or casual protocol compliance. Enthusiasm and interest are attractive but of little benefit if they wane under the demands of visit scheduling and query resolution. And don’t forget that those optimistic enrollment projections during initial discussions often fade into lackluster subject recruitment once the study starts. The success of your trial depends on timely completion and high-quality data. And both of those depend on the commitment and competence of your investigators. So, choose carefully.

Training

Sending a copy of the protocol to each investigator does not constitute effective training. Just as you should list the characteristics of the ideal investigator, you should define the essential understandings that you want each investigator to absorb from training. Whether your training is conducted in a centralized investigators’ meeting, through an online webinar, or in individual in-clinic sessions, it must impart those essential understandings. Design accordingly. And, if one or more investigators were not the most attentive students, retrain them as soon as possible. I cannot overstate the importance of effective training to the success of your next clinical trial.

Clinical supplies

Where is your study product being manufactured? Has supply adequate for the study already been produced? Are there any restrictions regarding its shipment? How is it being packaged, labeled, and distributed to the various investigative sites? What is your back-up plan if a particular shipment goes awry? How will you track each site’s inventory? These are just some of the questions that you will want to answer long before the first subject is enrolled.

Study initiation

Study initiation is one of the most exciting…and labor-intensive…activities of a clinical trial. It also is one of the most important. At no time during the study is the saying ‘Expect the best, plan for the worst, and deal with what actually happens” more appropriate than during site initiation. Getting each site off to a good start will build a foundation for consistent results throughout the study. The extra time that you spend planning…and conducting…each site’s initiation will pay huge dividends later on.

If you plan your next study, study your plan before launch to ensure that it is thorough, and then diligently execute your plan, your next study should run more smoothly than any previous trial. Will it be trouble-free? Of course not. There always will be the investigator who decides to retire one month after training, or the technician who calibrates the clinic scale using a bag of dog food instead of the proper weight you sent them, or the dispenser who unwittingly mixes the active and placebo inventories. But how quickly you catch and correct those mishaps will be a function of the thoroughness of your planning before the study even started.

I hope that you return next month for my tip on effective investigators! In the meantime, I’d love to hear your thoughts, comments, and suggestions regarding these tips…or the clinical trial process in general…and how we, together, might make it better.