March 13, 2018 | Norman Goldfarb is Editor of the Journal of Clinical Research Best Practices and Chairman of MAGI. His passion is advancing the practice of clinical research by standardizing best practices in incremental steps, so every day is better than the last. He joins Clinical Informatics News with a monthly column highlighting new ideas for advancing clinical research. This month he speaks with Chris Beardmore, CEO & Co-founder of Anova Enterprises.

Chris, what do you think it's about time for the clinical research enterprise to start doing?

It’s is about time clinical trials change their traditional focus from observing large groups of largely undifferentiated patients to the individual patient as the unit of observation.

What are clinical trials focused on the response of individual patients called?

They’re called “N=1” clinical studies. An N=1 study attempts to determine what makes a specific patient’s disease unique, and then uses that information to design treatment. In cancer, for example, there can be multiple omic factors (e.g., gene, protein or metabolome). Physicians and researchers would recommend a best treatment or combination of treatments for different combinations of these factors.

Does that mean each study will have just one subject?

Yes and no. Yes, in the sense that a treatment is tailored to each subject. No, in the sense that analysis of treatments and outcomes will reveal clusters of subjects in closely related or the same N=1 studies with good outcomes or even cures.

Don't you need at least two study subjects, with one as the control?

Actually, no, provided the disease process and related genetic and other variability is well understood.

Then why are studies still enrolling more than a single patient?

Four things have to happen: First, we need a much better understanding of most disease processes and individual variability. Second, biopharma companies, physicians, patients and regulatory authorities need a new mindset that favors very specific and accurate treatments over those that work on an unknown subset of patients. Third, we need to think of clinical research and clinical care as an integrated learning system. Fourth, we ne need a new economic model that rewards the biopharmas without punishing the patients.

Could N=1 data be collected in a different way?

Yes, the FDA’s expanded access programs should incorporate an N=1 methodology. Eventually, until a disease is completely understood, the treatment of every clinical patient should be an N=1 study.

What's been done so far and by whom?

N=1 trials have been undertaken. Nikles et al. set up a nationwide N=1 service in Australia for patients with attention deficit and hyperactivity disorder, where individual variations in intervention responses are common. There have also been studies examining the feasibility of N=1 trials from a cost perspective.

Well, Chris, we have our work cut out for us on this one, don't we?

Yes, and it's work well worth doing.