A qualitative study on the facilitators and barriers to adopting the N-of-1 trial methodology as part of clinical practice: potential versus implementation challenges

Figures & data

Table I. Overview of the major categories and themes based on the CFIR model.

Domain	Theme
1. Intervention characteristics	Reliability and validity
	Trial design
	Financial aspects
2. Outer setting	Paradigm shift towards personalized medicine
	Patient’s needs, resources, and perspective towards care
	External policy and incentives
3. Inner setting	Internal preconditions for implementation
	Continuous methodological education
	(Time) investment
	Ethical issues
4. Characteristics of the individuals	Patient skills
	Physician skills
	Patient acceptance
	Other psychological aspects

Table II. Overview themes, barriers, and facilitators for the domain intervention characteristics.

Theme	Barriers	Facilitators
Reliability and validity	Safeguarding validity in a real-world setting without blinding and randomization.	Triangulating subjective and objective data gives a more comprehensive overview.
	Uncertainty about which measurements patients can accurately do at home.
	Unexpected confounders and difficulty in determining causality.
	Patients may be able to distinguish the intervention from the placebo.
Trial design	Dealing with variation in the progression of a medical condition is challenging.	Informal N-of-1 trials provide great value for hypothesis generation.
	Complex interventions are difficult to standardize.
	Dealing with predefined treatment protocols can hinder tailoring the intervention to the needs of the individual.
Financial aspects	Expensive in the short term.	Reduce long-term costs by eliminating under- and overtreatment.
	Major time investments from healthcare workers.	Innovation grants from insurance providers.
	Insurance providers do not reimburse personalized treatments or medicines tried in a different context than originally intended.

Table III. Overview themes, barriers, and facilitators for the domain outer setting.

Theme	Barriers	Facilitators
Paradigm shift towards personalized medicine	System built on treating acute diseases instead of chronic conditions.	Personalized medicine is gaining momentum.
		Shared decision making is becoming increasingly commonplace.
		Patient-led communities are using informal forms of N-of-1 to improve their quality of life within chronic conditions.
Patient’s needs, resources, and perspective towards care	Patient attitude and health skills determine success of N-of-1.	Healthcare providers can harness proactive patient desires to try alternatives in a collaborative and relatively controlled setting.
		Patient feels taken seriously.
External policy and incentives	Communication and collaboration with insurance providers is difficult.
	Interprofessional collaboration does not happen enough.
	Data sharing is fragmented and hampered by privacy laws.

Table IV. Overview themes, barriers, and facilitators for the domain inner setting.

Theme	Barriers	Facilitators
Internal preconditions for implementation	Logistics are challenging if patients live far from the clinic.	N-of-1 trials may be more easily accepted in an academic hospital with an additional research focus.
	Setting up a baseline is challenging, making it difficult to interpret findings.	Informal N-of-1 trials may be good enough for tailoring treatment plans.
	Reliable data infrastructure is lacking.
Continuous methodological education	Clinicians can allocate limited time to staying up to date about new approaches and methodologies.	N-of-1 trials must be incorporated into medical curricula.
(Time) investment	Requires significant time investment from healthcare providers.
	Organizational incentives and rewards for personalized care are often low.
Ethical issues	The patient will be deliberately misinformed during the trial.	Patients are willing to give ethical consent if it will result in health gains for them or their community.
	The patient will not have access to their data until after the trial.	Providing care according to non-optimized processes (i.e., not N-of-1) might be considered unethical.
	The patient will have to engage in blocks of placebo or alternative treatment even if the experimental treatment is effective.

Table V. Overview themes, barriers, and facilitators for the domain characteristics of the individual.

Theme	Barriers	Facilitators
Patient skills	Not all patients can handle the relatively tedious task of continuous data gathering.	Patients who understand why they are given a certain treatment are more likely to be motivated and therapy compliant.
	Not all patients have sufficient insight in the fluctuations in their physical condition.
Physician skills	Not listening well enough to the patient’s needs and conception of their disease.	Shared decision making is becoming more accepted in medical practice.
		The importance of basic coaching skills in shared decision-making is being recognized.
Patient acceptance	Strong patient beliefs may hinder acceptance of treatment.	A physician’s enthusiasm for a certain type of treatment and N-of-1 for the benefit of the patient can help to change a patient’s attitude.
	Cultural differences in beliefs are not always accounted for.
Other psychological aspects	Full trust between patient and healthcare provider is not always present.	Recognition for patients’ efforts and close involvement of healthcare providers can make patients feel understood.
	A patient’s past negative experiences can lead to resistance to new treatments.	Patients altruistically contribute to science, and their results can help their fellow patients.
	Willingness to transition to new treatment block in N-of-1 trial is low if patients do well on a certain treatment.
	Continuous measurement at home may make patients feel more ill than they are.

Figure 1. Barriers and facilitators comprising key barrier 1.

Figure 2. Barriers and facilitators comprising key barrier 2.

Figure 3. Barriers and facilitators comprising key barrier 3.

Figure 4. Barriers and facilitators comprising the key facilitators.

Figure 5. Potential interaction between barriers and facilitators.