N-of-1: Clinical Trials for One Person; A Solution or an Impractical Workload?

 

The concept of N-of-1, or personalization of clinical care, originated in the 1980s according to an article in The Scientist.

It began with a sixty-five-year-old Ontario man who was being treated for extreme difficulty in breathing.  His doctor prescribed several medications for asthma.

The treatment consisted of ipratropium bromide and albuterol together with the oral steroid prednisone. Added to that was theophylline which has an anti-inflammatory effect.

After months on this regimen, he had no relief from symptoms. His case was brought to the attention of McMaster University’s Dr. Gordon Guyatt.

Dr. Guyatt had an interest in a novel clinical trial he had heard about whereby a patient and his doctor tested the efficacy of a treatment over several months.

The asthmatic patient seemed like the ideal candidate as his reasonably stable and chronic condition would probably not be resolved before test completion.

The doctors had doubts about the efficacy of theophylline and ipratropium bromide. Therefore, a protocol was designed by Dr. Guyatt and his team where the drugs would be administered to the patient for ten days and then the placebo would follow for ten days. This regimen would continue until the patient and his doctor agreed to conclude the experiment.

The placebo and the drugs were crafted identically. The patient would be responsible for rating his symptoms. At the same time, he would continue to take his other three medications as he normally would.

After four rounds the trial results were analyzed. It was clear to the doctors that theophylline was partially the cause of the patient’s breathing difficulty. They stopped the drug.

On the other hand, a subsequent trial proved that ipratropium bromide was improving the patient’s symptoms.

The trial was included in a 1986 paper arguing for the implementation of personalized trials. The argument was made that an individual patient would benefit and avoid being treated with ineffective drugs.

About the Next Phase

Dr. Guyatt and his team then set up N-of-1 services at McMaster University. Physicians from local medical communities could test the system for their patients. They could also refer patients to the McMaster trials.

Dr. Guyatt and others who were trained in the protocol oversaw these trials and joined the physicians in designing specialized therapies. They also assumed the responsibility of working with the pharmacists to source the placebos and drugs as well as collecting reports from participants.

By the late 1980s, the team had completed fifty-seven trials with fifteen resulting in changes to patients’ treatment.

The Case for Personalized Trials

Personalized trial details will vary between individuals but analyzing all trials in a particular series will reveal trends and capture patient response to treatment.

The majority of clinical trials are designed generally with two groups. One is an experimental group that receives the drug being analyzed. The second group either receives a placebo or another brand of drugs. The patients are randomly assigned to an experimental group or to a control group.

The downside, according to proponents of personalized trials, is that standard trials do not provide in-depth analyses of varied treatment responses.

A study conducted by the University of Queensland reported positive results for eighty-five percent of patients who had completed its N-of-1 trial for ADHD.

These patients stayed with the treatment after the trial ended for a minimum of one year. The study leaders suggested that boosting adherence can eventually be cost-effective.

The Case Against N-of-1

Opponents of N-of-1 refer to its slow acceptance by the research and health care communities. They attribute a lack of enthusiasm by some sectors to the workload involved in attempting to personalize research to such an extreme degree.

Richard Kravitz researches internal medicine at the University of California. Kravitz and colleagues have, using the N-of-1 program, monitored approximately two hundred individuals with chronic musculoskeletal disorders.

The patients reported that they had greater involvement in their own medical decisions and in managing their pain.

A Third Scenario

University of Exeter’s Nicky Britten and her colleagues are investigating the attraction to N-of-1 trials by people who have behavioral and mental disorders. She believes that some conditions are better suited to individual trials than others.

In a way, these arguments bring opponents and proponents together. Both sides agree that personalized trials can be of benefit to some patients more than others.

 


Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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