All The World’s A Stage

Featured Blog by Denni O. Day

I’ve often thought of clinical trials as theater. As director, I know the playwright and the producer. Having read the script, I know the plot. All that I need for a box office bonanza is a killer cast.

While each role contributes to the story, the choice of protagonist can make or break an entire production…just as the choice of investigators can spell success or failure for a clinical trial. What would you be looking for during auditions?

Some companies prefer to conduct their clinical trials in-house using a select group of veterinarians as their investigators. This practice eliminates much of the uncertainty inherent in different groups of investigators but it could reduce the level of investigator objectivity. Other companies outsource some or all of their studies, but insist on investigators with previous trial experience. Such investigators might be easier to train, but may come with preconceived notions of proper trial conduct and other bad habits. Still other sponsors recruit investigators through broadcast-fax casting calls and hope to find a few stars.

When I started managing clinical trials, I thought experienced investigators would produce better results. Unfortunately, VICH GL9, Good Clinical Practice (3.1.2), provides minimal guidance regarding investigator qualifications: “The investigator should have sufficient knowledge, scientific training and experience…” On the human side, the FDA’s November 2012 draft guidance document offers even less direction: “The regulations do not specify the minimum requirements nor do the regulations specify what qualifications an investigator must have in order to be considered qualified by training and experience to conduct a study. Sponsors have discretion in determining what qualifications will be needed…”1

Once I had completed a few studies, I discovered that “experienced” investigators were of two types: Type 1, who skim the protocol and ad lib their way through the trial because they “know what to do” and, Type 2, who memorize their lines and follow the protocol exactly. Like theatrical prima donnas, Type 1 investigators may perform but can be a source of protocol deviations, sloppy data, and non-evaluable cases. By contrast, Type 2 investigators usually enroll quickly, rarely include an ineligible case, and generally produce better data.

The stark contrasts between these two types led me to search for the characteristics that drove Type 2’s superior performance. Then I began to look for those same traits when recruiting veterinarians who lacked prior trials experience. When the performance of these “inexperienced” investigators mirrored that of the Type 2 investigators, I knew I was onto something.

Over time, I developed my list of traits into an extensive checklist to screen potential investigators. Anyone can create such a checklist by analyzing the performance of their investigators and then cataloging the parameters that distinguish one from another. Using such a checklist to select investigators for each subsequent study ensures that every trial involves investigators who have either the “right” experience or the “right stuff.”

So, what traits result in superior investigator performance? I group them into three categories: attitude, dedication, and ethics. An investigator with a friendly, willing attitude is easier to train, open to suggestion, more accommodating when it comes to scheduling monitoring visits, and simply more fun to work with.

Also look for veterinarians who truly love what they do. Their dedication shows in their questions about the protocol and suggestions for improving the study design or simplifying the data forms. They are active participants during training and clearly enjoy interacting with their colleagues. A possible new treatment for the study’s indication and the related science are their primary motivators, not the budget. Some of the best investigators probably would do the work for free just to help their patients.

Lastly, hold investigators to the highest ethical standards. Anything less is a violation of the sponsor’s trust and a disservice to the individual subjects. All data must be recorded as observed and all missing data must be documented properly. Investigators who falsify or fabricate even one data point are unethical and a serious risk to the study’s success. No one should tolerate such behavior.

To paraphrase something a colleague told me long ago when I worked on the human side, every good investigator is a veterinarian but not every veterinarian is a good investigator. By carefully choosing investigators for your next study, you will dramatically improve your chances of getting a standing ovation when the curtain falls.

1Guidance for IRBs, Clinical Investigators and Sponsors, Food and Drug Administration, November 2012 (draft), page 4 (#5)