A friend says n-of-1 experiments are unscientific — what gives?

It’s easy to see why many people, even some doctors, believe n-of-1 studies are “not statistically valid.”

Many doctors weren’t exposed to the voluminous literature on N-of-1 studies in medical school or, if they were, quickly forgot the concept. Once they moved into clinical practice, they’ve been inundated, day after day, by drug reps justifying their drug’s superiority over others based on large parallel group random control trials (RCTs).

“This study of 3,500 patients shows that our drug X results in a 17% improvement in symptom Y,” says the drug rep, pointing to the study’s title. Parallel group RCTs are often perceived as the “gold standard” for proving a drug’s efficacy and safety.

In fact, statisticians have long argued that the results of RCTs are not generalizable for any given individual.

First, the RCT’s participants often have nothing in common with a given patient, whether because of age, sex, fitness levels or other variables. Historically, women and minority groups in particular have been underrepresented in studies.

Second, even if a study’s participants do appear to match the patient, research indicates that drug efficacy varies strongly from patient to patient, whether because of genetics, microbiome or behavior. Behind the headlines of all large studies reporting “average” benefits is compelling evidence that most drugs don’t work equally well for all people. This is called “heterogeneous treatment effects,” or HTC.

“All RCTs do is show that what you’re dealing with is not snake oil,” according to William R. Shadish, PhD, a professor of psychological science at the University of California at Merced. “They don’t tell you the critical information you need, which is which patients are going to benefit from the treatment.”

This means that, for an individual, a drug can’t be proven to be effective, much less optimal, unless it’s been systematically tested for that individual, ideally with crossovers, placebos and blinding. In short, an n-of-1 trial.

In fact, it’s the trial-and-error drug experiments (formally called “trials of therapy”) used by most doctors to find the best drug for an individual patient that lack scientific rigor. “These so-called trials are unblinded, have no control, and involve no formal assessment of effectiveness, making them vulnerable to invalid conclusions about treatment response,” observe Dr. Sunita Vohra and Salima Punja, BSc.

>> More on the difference between n-of-1 trials and large group RTCs.

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