Ever wondered how easy or hard it might be to run a clinical trial, or what researchers have to do to be able to run a study? Here we’ll outline some key differences between an academic study and an FDA-regulated study, and talk about our own ketamine clinical trial planned to start this fall. If you didn’t realize there were 2 types of studies, you’re not alone.
An academic study is one where the physician or researcher at the site often takes full responsibility for the study design, conduct, and reporting, and acts alone to complete the study or may work in collaboration with a pharma company to use a treatment supplied by them. Often an academic study is done in one or a few centers. The researcher receives permission from their local regulatory body, the Institutional Review Board (or IRB), to conduct the study at their site. Every site that performs research will have an IRB to regulate and approve research. In a drug study for example, IRBs often consider how often the patients come to the clinic, what dose levels the patients receive, and ensure enough safety measures are in place to protect patients. Only studies that are IRB-approved may be conducted.
Once the academic study is approved, the study can begin to recruit patients and treat them exactly as described in the protocol. All patients must provide written informed consent to participate in the study. Deviations from the protocol are not allowed and often need to be reported to the IRB so they can assess if the patients are at an increased risk due to the deviation. At the end of the study, the researchers can analyze and write up the data collected, often from excel spreadsheets, and publish their findings in a scientific journal.
An FDA-regulated study, in addition to meeting local IRB requirements, must also adhere to federal regulations as well as international standards for data integrity and patient protection. FDA requires an auditable database for the study data, which means a database (most often an electronic database) must be designed and built with the ability to track changes to the data points, know who changed them, why, and when. All data must be submitted to the FDA as well as they will conduct their own analyses on the data, which is important especially if the study sponsor is trying to get a new drug on the market.
Another requirement is data monitoring, which means independent consultants must review the data collected, verify that the data corresponds to a real patient, and the data recorded in the study database is accurate representation of the patient’s medical record. Once the database is considered clean and no more changes or updates are needed, the database is locked. A pre-planned statistical analysis will be performed on the dataset to determine safety, efficacy, and other outcomes planned for the study. The statistical analysis plan for the study is completed prior to the database lock to ensure analyses aren’t biased and altered based on the results of the study.
In addition to the statistical analysis plan, every other aspect of governing the study must be clearly documented so that FDA can review how the study was conducted, how it was recorded, and how compliant the research was with the study plan. Due to these requirements, most FDA-regulated studies are conducted by pharma companies and their affiliates who specialize in these types of tasks and documentation. The pharma company is then responsible for meeting all of the FDA requirements for their FDA-regulated study.
However, academic studies may also be regulated by the FDA, and often FDA-regulation is requested by researchers if a treatment is being used differently than intended as in a new route of administration (IV to oral, for example), in a patient population that is considered vulnerable (children, for example), or for a disorder where patients can’t consent to the research directly (as in a neurodevelopment disorder like Rett syndrome). RSRT is funding an FDA-regulated academic study to evaluate ketamine dosed orally in Rett syndrome patients aged 6-12 years, for exactly these reasons. We are glad to know that our study will be held to the highest standards as industry-sponsored studies are, and we are hopeful that our ketamine study will provide additional experience to our Rett Investigators to facilitate the success of other FDA-regulated research in Rett syndrome. To learn more about our clinical trial, visit www.clinicaltrials.gov and search “Rett Syndrome” and “ketamine”, or NCT 03633058.