Disruptive technology with a $40 per patient clinical trial price tag...
The randomized clinical trial (RCT) is the gold standard for clinical research. In an RCT, patients are recruited and enrolled into a study, assigned one treatment or another randomly, and followed-up as their disease of interest progressed or improved. Outcomes are compared between the treatment groups, and standard statistical tests are used to analyze the results to ascertain whether one treatment is better than the other.
Because the rigor in establishing causality using this procedure, RCTs are the basis of establishing effectiveness for the vast majority of medical treatments. RCTs are also used by the Food and Drug Administration (FDA) and other governmental agencies in the approval for specific medications or medical devices.
As consumers, we can feel somewhat reassured that the FDA stamp means a set of data has been reviewed such that the medication has been convincingly shown to be effective, and the side effects are under control and predictable.
The Value of RCTs
Despite well-known, albeit rare, mistakes (i.e. Vioxx), RCTs are one of the most instrumental developments in modern medicine, providing a firm scientific foundation for all existing treatments. They are the heart of evidence-based medicine (EBM).
RCTs and related methodologies also have deeply contributed to a wide variety of other disciplines, including public policy, marketing and operations research, and education. In fact, some have argued scientific rigor of RCTs makes discoveries through large RCTs more convincing than many basic research results because of the careful control, larger sample size, and common practice of multiple replications. There are numerous examples in which results of RCTs point to important insights in disease processes that are subsequently further studied in animal models ("top-down translation"). However, RCTs have a few problems:
- RCTs are Expensive
Everything about RCTs is expensive. It costs about $15,000 (conservatively) to randomize one patient in a traditional RCT. Effect sizes are often small and a large number of patients have to be enrolled. For a modestly sized study of 100 patients, the simple act of getting enough patients would cost approximately $1.5 million. And that's not counting the cost of expertise for analysis, execution, and safety monitoring throughout the study.
- RCTs may not be Generalizable
You can test treatments and follow patients in ideal situations, but people in the real world do unpredictable things. They drop out of treatment. They move. They develop other diseases that would disqualify them from entering the study in the first place. This begs the question: Are the results from your study really applicable in the real world?
Here is the Uber-ification idea for RCTs: Is it possible to peg electronic medical records to a centralized research facility so that each time a diagnosis is made in the community it automatically triggers a protocol that begins the enrollment, consent, randomization, follow-up process?
Safety monitoring would be conducted by the physicians the patients see and improving generalizability would be a no-brainer.
The idea behind this study is the Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia (TASTE) trial. The New England Journal of Medicine hailed it as the next "disruptive" technology in clinical trials. The perspectives article, which aims at non-specialists, is worth a read. In the TASTE study, people with a specific kind of heart attack were randomized to either getting thrombus aspiration or not (which is a procedure that occurs during "Percutaneous Coronary Intervention", a jargon that means, colloquially, stenting). The most remarkable thing is that they were able to randomize 5000 patients at around $40 each by using a standardized electronic medical records system.
Basic schematic of how registry based research can be funded and operationalized. The data streams need to be provided by current users of EMR registries, which would be designed by centralized investigators. Publicly funded research would support specific initiatives that have important public health concerns but may not be profitable. Privately funded research would R&D potentially profitable programs. End users would be hospitals and consumers who look for data driven "precision" care.
Maybe this is only doable in Scandanavia; maybe not. We probably have the resources here in the U.S. - if we can leverage productive private-public collaborations. The enrollment of large integrated care systems (e.g. Kaiser) is larger than the entire population of some Scandinavian countries. And while it is often hard to make regulatory headway (i.e. centralizing EMR) in the U.S., it tends to be faster to push these initiatives through in a private system with large Managed Care Organizations/Venture Capital/foundations and other alternative funding sources.
Questions Related to Addiction and Substance Abuse
So, what are some addiction-related questions I would like answered if we had a system like that? I would perhaps consider redoing PROJECT MATCH for psychotherapy. I would consider a large RCT on the efficacy of telemedicine-driven TES and, of course, various medication comparisons.
What else should we consider? What is an easy outcome? For heart attacks mortality is the easiest outcome. For substance abuse, it's not so easy. The crown jewel organization in large multi-center RCTs substance abuse research is the National Institute of Drug Abuse Clinical Trials Network. People just started thinking about these issues in the newly formed Data Science Task Force.
One thing’s for sure: we are dying for all the help and ideas we can get.
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