In “Gaga Over Clinical Research” (June 3, 2001), I noted that, while all investigators are good veterinarians, not all veterinarians make good investigators. Some have practices that are too small. Others are too busy. A few would participate in clinical trials for the money but, otherwise, don’t care. Some like the idea but can’t seem to follow the protocol. And then there are those who have participated in several clinical trials and, therefore, “know it all.”
Sorting through a list of veterinarians to find those who really care about the science, truly understand their responsibilities, and are willing to commit the necessary time and effort to generate superior results is a challenge.
So, in today’s highly-competitive, time-sensitive environment, how does a project team quickly find a group of investigators who will help them get their clinical trial completed? For expediency, some teams return to the same roster of investigators over and over, regardless of prior shortcomings or little experience with the indication. Others cast their lot with fate and send out email or fax solicitations to as many veterinarians as they can identify.
A better way would be to identify veterinarians who specialize in, or have extensive experience with, the study’s indication, and then recruit them. Please note that I said a “better” way. As with many things in life, “better” is rarely “easier.” Nonetheless, since the quality of the study data will determine the success or failure of the entire study, doesn’t it make sense to search for better investigators?
Let’s say that you have identified a group of veterinarians who look good on paper, sound good over the phone, have a nice web site, and are interested in participating in your trial. You even may have visited them and were impressed by their presentation, their clinic, and their staff. Certainly all good signs… but will they be good investigators? Whatever your decision metrics may be, your final choice will boil down to one key parameter: trust.
Whenever I hear the word “trust,” I am reminded of two famous phrases. The first is “In God We Trust,” the official motto of the U.S. that has adorned its coinage since 1864 and its paper currency since 1957. A corollary, which appears above many a cash register, states “In God, we trust, but all others must pay cash!” Apparently, some proprietors feel that trust is something rarely (if ever) extended beyond the Almighty. During clinical trials, however, we have few options other than to trust our chosen investigators.
Which brings me to the second phrase: a Russian proverb (Doveryai, no proveryai) that Ronald Reagan used often during the 1980s when discussing nuclear disarmament (Trust, but verify). This advice, while not fool-proof, is very helpful for controlling the risks inherent in outsourcing clinical research and, thus, enhancing the final results.
To illustrate these concepts, I’d like to share two real-world stories. To spare the guilty, I have changed names and locations.
Erik Jensen, a senior study monitor for a contract monitoring firm, has developed a healthy skepticism when it comes to investigators. He believes that most have good intentions but he also knows that the demands of a busy clinic, the carelessness of a technician, or the forgetfulness of an owner can undermine the best of intentions. He is willing to trust an investigator but he learned the hard way that trust should never be blind.
Dr. Rancone, the owner of Rocky Heights Veterinary Hospital, was one of the very first sites that Erik visited as a new monitor. During the site qualification visit, Dr. Rancone proudly boasted that she had “many years” of clinical trials experience and, consequently, would be a good investigator.
“I always wanted to participate in clinical research. But, once I began offering trial opportunities to my clients, I also realized what a great business it is. I actually can make more money from studies than I do from my practice. Rest assured, I’ll be one of your top sites.”
Erik was impressed by Dr. Rancone’s study experience. He also thought that her economic motivation would spur her to enroll more subjects. Since the sponsor’s
study team was looking for high-enrolling sites, Dr. Rancone seemed to be a perfect fit. Erik recommended Rocky Heights as a study site and trusted that Dr. Rancone would do a good job. He later would learn that boasts and promises do not justify trust.
By mid-study, Rocky Heights had enrolled the third highest number of subjects. Unfortunately, they also had the second highest number of protocol deviations and the highest number of queries. During his first interim monitoring visit, Erik discovered that Dr. Rancone had instructed several “busy” owners to administer two tablets every other day, rather than the specified one tablet every day because she thought it would be “easier” for them. The test article inventory did not reconcile and no one at the clinic knew why the numbers did not add up. Then, the treatment administrator admitted that they had not been collecting the owner diaries at every visit because Dr. Rancone felt it would be too much of a burden for the owners to bring them to their study visits.
When Erik asked Dr. Rancone why she was not following the protocol, she said: “Trust me. You’ll know that I did the right things when you see my data. It’ll be perfect.”
Those two words haunted Erik throughout the rest of the study as he struggled with the mediocre results from Rocky Heights. It was a very painful lesson for a new monitor. Fortunately, it was one that Erik has never forgotten.
“I got it. I got it. I know exactly what to do. Look, I read the protocol. I’m ready to enroll.”
Now a senior monitor for three years, Erik had heard this line many times. It went in one ear and out the other. Erik smiled politely and continued with his site qualification checklist for City Lights Animal Care Center. Just as Erik started to ask about the clinic’s client population, Dr. Flannigan interrupted: “Look, you don’t have to go through this with us. I know what I need to do so this trial gets done on time. Trust me.”
Two little words that told Erik he really needed to complete his checklist…despite Dr. Flannigan’s sighs and eye-rolls. When he had finished, Erik asked Dr. Flannigan and his team if they had any questions.
“Nope. We’re all set,” confirmed Dr. Flannigan. He quickly signed Erik’s site qualification visit report and, with a big smile, said: “We’re going to be your favorite site. We’ll be the first to reach our enrollment target, and our data will be great. Trust me.”
Two little words that ask so much, yet give so little. Erik packed up his bag, wished everyone well, and left the clinic. As he was driving to the airport, those two little words kept buzzing in his ears. For now, Erik gave Dr. Flannigan the benefit of the doubt. But, beginning tomorrow, he would pay special attention to Dr. Flannigan’s site.
Unlike the first story, this one has a happy ending. Dr. Flannigan, for all his bravado, proved to be an excellent investigator. He followed the protocol exactly, and his documentation was timely, thorough, and accurate. He quickly resolved queries and did not repeat errors. His study staff was equally dedicated and responsive. Even the owners’ diaries were mostly complete, and those with missed doses were supplemented with explanatory notes. Dr. Flannigan had justified Erik’s trust.
So, in the context of investigators and clinical trials, what is trust? And how is it earned?
Trust is one person’s feeling of confidence in the consistent reliability of another person. Promises alone do not generate trust but performance aligned with those promises does.
One little word. That means a lot.