Welcome to the fifth installment of this 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.
Not many studies reach that goal. Instead, they struggle with sluggish enrollment, vague and infrequent communication, sloppy and missing data, ineligible subjects, cost overruns, and avoidable protocol deviations. Why? The reasons are many, but they all derive from a lack of clear focus on the true objectives of every study: timely completion and high-quality data.
It’s not that study managers don’t want their trial to finish on time and deliver quality data. They surely do but, in their rush to get started, they too often rely on “comfortable” and “safe” measures that frequently fall short. For example, they recruit investigators from past studies who may not have the requisite patient populations or even be interested in the target indication. They rely on “experienced” monitors who may be travel-weary, careless, or impaired by bad habits. In short, they focus on the (familiar) means and not the (essential) end.
For a study to be truly successful, the desired end result must guide the selection of participants and the coordination of all study activities. This series will help you refine your focus and improve your process so that your next trial is a resounding success!
For those just joining the discussion, let’s review previous tips:
Tip #1. Clear Expectations. One of the most effective ways to prevent problems during a clinical trial is to set clear expectations for all project team members before the study even begins.
Tip #2. Comprehensive Planning. Planning for each phase of the clinical trial must involve all members of the project team and be comprehensive, detailed, and unambiguous.
Tip #3. Effective Investigators. Every investigator is a veterinarian, but not every veterinarian will be an effective study investigator. Only those who truly understand Good Clinical Practice Guidelines, actively recruit study subjects, and then closely follow the protocol will produce superior results.
Tip #4. Rigorous Training. Every study participant must have a thorough understanding of the protocol, their individual responsibilities, and the sponsor’s expectations. These can be imparted in a centralized training meeting, on-site instructions, or a webinar presentation. However, regardless of the training format, refresher training should be provided early and often to ensure continued protocol compliance and quality data.
Now, on to Tip #5: Proactive Subject Recruitment.
As I’ve noted on many occasions, 90% of all clinical trials experience significant delays, and a primary cause of those delays is slow enrollment. So, this definitely is a subject (pardon the pun) deserving our attention. There is no question that the more complex the protocol, the more challenging the enrollment. But there are several steps that every project team can take to make that challenge a little less daunting.
First, review the protocol with several high-performing potential investigators, paying special attention to the inclusion/exclusion criteria. Are all of the demographic, age, gender, prior treatment, and concomitant medication restrictions absolutely essential to the profile of an acceptable subject? Can wash-out periods be re-evaluated to allow more potential subjects? Have any important restrictions been overlooked? You would be surprised how often this exercise results in protocol amendments that boost enrollment.
Second, spend the time to comb the medical records of potential investigators to refine their enrollment estimates. Since veterinarians, by nature, try to please, their projections tend to be optimistic. Sometimes, one of the study technicians or the clinic manager has a better feel for potential enrollment than the investigator, so be sure to ask other members of the clinic staff for their thoughts.
A simple and usually free method of advertising for potential subjects is to include sponsor-approved information about the clinical trial on each participating clinic’s website and/or blog. Many clients interact with their veterinary team online, so digital advertising is a great way to expand awareness of the trial. Similar information can be included in the regular newsletters and other mailings that many clinics publish.
Another relatively easy and inexpensive way to advertise the trial is for each clinic to send a sponsor-approved mailer to each of their clients. While this method may seem wasteful since not all client animals are likely study subjects, it often identifies new pets in certain households as well as existing client pets that previously had not exhibited relevant symptoms (such as itchy skin, lameness, or incontinence). These mailers sometimes find their way to friends and family whose pets also might qualify for the study.
For especially challenging inclusion/exclusion profiles, there are more elaborate (and costly) enrollment enhancement programs like colleague referral bonuses, newspaper and radio advertising, enrollment contests, and other incentives to attract more study subjects. Depending on the study, the project team may want to plan (and discuss with the sponsor) one or more of these more aggressive techniques to deploy if enrollment lags once the study is underway.
Once a potential study subject has been identified, many clinics rush to schedule an appointment and sign them up for the study. Not so fast! Finding a potential study subject is only half the battle. Confirming that each subject truly satisfies the inclusion/exclusion criteria AND (this is the step that many clinics fail to complete) also determining whether each subject’s owner will fulfill their study responsibilities are equally critical elements of successful enrollment. Failing to ask whether an owner has planned vacation or surgery during the study period can result in missed study visits, inconsistent dosing, sketchy owner diaries…or worse… that often disqualify their pet before the study ends. Also, clients who are lackadaisical about their pet’s care, non-compliant with previous medication regimens, or careless about scheduled clinic appointments probably are not promising study candidates. Moreover, unless the protocol allows it, investigators may not enroll their own animals in a study or serve as surrogate “owners” for strays or shelter animals.
Enrollment can be challenging for almost any study. However, a detailed review of the protocol’s inclusion/ exclusion criteria, comprehensive team planning, thorough mining of each site’s patient population, online site advertising, and a backup marketing plan will help maximize subject recruitment. Then, a realistic assessment of each subject owner’s commitment to their study responsibilities before signing the consent form will increase the likelihood that each subject will complete the study and that owner-supplied information will be protocol-compliant. These two factors, combined with diligent investigator performance, will result in high-quality data.
Which just happens to be the subject (there’s that pun again!) of my next article. Please join me!
In the meantime, please let me know your thoughts, comments, and suggestions regarding these tips… or the clinical trial process in general…and how we, together, might make it better for all of us.
Thank you and see you next month!