“If you don't know what you want, you end up with a lot you don't.” ― Chuck Palahniuk, "Fight Club" 1999
I have been a clinical investigator for 16 years, engaged in phase I to IV company-sponsored trials as well as NIH and investigator initiated studies. There are certain rules - written and unwritten - for participating in research as an investigator.
Being part of clinical trials is like joining an elite club—it is by invitation only, and things can get ugly if you are unfamiliar with the process. Clinical trials are important in the drug approval process and can help augment a clinician’s resume and support salaries, but if not conducted properly, they can ruin your reputation and land you in jail, even if you are not the problem. This document will help you navigate this process and allow you to be successful and fulfilled by medical research.
Rule 1: Understand your goals
What do you hope to gain by conducting a clinical trial? Do you want to make a name for yourself? Get your name on important publications? Are you interested in making extra income? Is this a requirement of your employment? Is there a specific clinical question that needs to be answered, and you want to be part of this process? Perhaps you want to help your patients’ access medications they would not otherwise be able to get?
Based on your specific goals, choosing a clinical trial that suits you and your needs will allow for smoother contract negotiations and facilitate enrollment. The trials that Dr. Cush and I select are usually based on a novel concept, potential for patient benefit, and won’t lose money. Be realistic about how many patients you can enroll. Many investigators tend to overestimate the number of subjects they can enroll so their site will be selected, but this can backfire. Budgets are based on how many patients will be in a study; if the sponsor finds that you are under-producing, you may not be invited back to play or end up returning monies provided at the start.
Rule 2: Avoid losing money
Contracts and budgets are long, tedious, often boring, and time-consuming. Legal terms sound like a foreign language. Your initial instinct is to sign what is placed in front of you because you feel that the lawyers have already hammered the terms out with other institutions. If the other guy thinks the contract is okay, then it must be okay.
Take your head out of the sand; what works for one facility is not a one size fits all. Check the line items; consider reasonable tangible and intangible costs and put it in the budget: cost for facilities, cost for training and retraining (BILAG training can take hours!!), cost for switching monitors (this latter can be gigantic sinkhole of time), and cost of monitoring visits (lost income). You need someone to be masterful at contracts and budgets to insure you don’t lose money.
Note that monitors of your studies are either employed by the the pharmaceutical sponsor or may be provided by independent contract companies called clinical research organizations (CRO). Their job is to ensure the accuracy of the data collected and that the protocol is followed according to Good Clinical Practice (GCP) guidelines.
What you may not know is that the monitors, especially CRO monitors, may be padding their "billable hours" to profit the CRO or themselves. They may do this by extending their visits, or scheduling multiple visits to “complete their job.” You need to set the rules for your research site: no more than one monitor, for one day each month; any more than that needs to be approved, negotiated or become a contracted mandated charge for you and your coordinator time.
If your goal is to avoid losing money doing research, restate it: your goal is to be profitable. There is no such thing as “breaking even”.
Rule 3. Know your studies and know your patient population
I like to talk to other practices who are conducting clinical research trials to gauge how they are doing; many have a hard time recruiting. Some practices have 8-10 rheumatologists, but usually the only one who is actively recruiting is the principal investigator.
Even though the other rheumatologists are listed as sub-investigators, they usually do not contribute. They may be disinterested, unmotivated or distracted. Most are incapable of remembering they are trying to recruit for a trial while the perfect study patient is sitting in front of them in the clinic. Successful recruiters are ones who will always consider research as a treatment option when change is needed. All investigators should fully understand the potential benefits of the study and have conviction that the study is good for patients and good for your facility. If the investigators are not convinced the study is benefical, why even participate? How can they convince the patients of the potential benefits of the trial if they do not believe in it themselves? The real trick is finding who amongst your peers is capable and interested in doing research.
If you are committed to recruiting and enrollling patients, the first step is understanding the drug or study question under examination; the next step is familiarity with the inclusion and exclusion criteria. In our practice, all patients who establish care with us know that we conduct research; at their first visit, they are asked if they have interest in participating in clinical trials. We also keep a list of studies with abbreviated inclusion/exclusion criteria in the exam room to remind us to review whether or not the patient in front of us would be a good candidate for the study.
Often, investigators will only approach certain patients about participating in trials: patients without access to care, retirees, or those who have failed every conventional treatment. These investigators, unfortunately, miss opportunities to enroll patients who might otherwise be good candidates.
I have study patients who are professionals and hold full-time jobs, some travel from far away, and many just want to participate because they like to be part of “cutting edge” medicine. Finally, talk to your colleagues. Let them know you are conducting a trial and share with them how important the study is. Ask your patients who are already in the study if they know anyone else who might benefit from the trial. Word of mouth is very important.
Rule 4. The buck stops here! You are the boss.
By signing the 1572, a form that holds the investigator responsible for the conduct of the trial in accordance to FDA regulations, you are personally accountable for everything.
In 2006, Dr. Eric Poehlman was the first scientist to be imprisoned for falsifying a grant application. He fabricated scientific data on obesity, menopause and aging for over a decade while receiving millions of dollars in federal grants from the National Institutes of Health (NIH). His lab oversaw students and postdoctoral researchers, carrying out his projects. The guilty verdict led to the retraction of 10 scientific papers, and he was banned forever from receiving public research money.
Subsequently, other researchers have been indicted: Dr. Scott Reuben, an anesthesiologist, spent half a year in federal prison for contriving data in his studies with Pfizer. Dr. Dong Pyou-Han was arrested and charged with falsifying his data on a potential HIV vaccine. Scientific fraud is considered a crime. Perhaps these researchers' mistake was lack of oversight of their postdoctoral students versus intentional malfeasance; the law and federal government do not care. They only care whose name is on the 1572. While you rely on your research coordinators and monitors to alert you of problems, ultimately, you are the one accountable for how the research is going at your site. There are no shortcuts.
Speak up if you find issues with the study process, particularly if it pertains to the safety and integrity of the trial; talk to your colleagues who might have similar problems. There was a central lab that would not process our samples properly, and we had to resubmit samples multiple times; the duration it took for results to come back made our patient miss the screening window. The patient was screen-failed and rescreened again; unfortunately, the same lab issue happened again. The patient and I felt like we were in a hamster wheel, unable to get off. The patient was a perfect candidate for the study, but the labs took too long for him to enroll within the window.
The lab blamed us, claiming my coordinator did not send the tubes in proper containers or the tubes were missing. We had two coordinators and a research manager check and recheck the tubes of blood prior to sending them out, but we still had issues. I talked to other sites who noted similar complaints. We finally were able to resolve the problem but only after escalating it to the medical monitor.
One final note: if the study is frustrating despite your best effort to make it better, it is okay to quit that study and find a company, drug and trial that facilitates good research where you want to be part of the action.