Table 1. Indications and contraindications for single-patient trials (SPTs).
| Feature | Description | Indication | Contraindication |
|---|---|---|---|
| Heterogeneity of treatment effects (HTE, [8]) | Treatment effect varies across patients; one size does not fit all | With HTE, evidence based on specific patient is essential to personalize treatment decisions (e.g., serotonin reuptake inhibitors for treatment of depression) | Homogeneity of treatment effects (e.g., insulin [titrated to need] for reduction of blood glucose) |
| Chronicity | Long-term treatment for chronic condition | Chronicity allows knowledge gleaned from single-patient trials to inform future treatment decisions (e.g., gastroesophageal reflux disease) | Acute conditions (e.g., influenza) One-time treatment with long-lasting effects (e.g., surgery) |
| Stability | Stable treatment effecta | Stability ensures that knowledge gleaned from single-patient trials informs future treatment decisions | Lack of stability (e.g., in an individual whose dietary intake of vitamin K fluctuates widely over time, the effects of warfarin may be unstable relative to the effects of aspirin) |
| Effect onset and carryover | Transition periods between two treatment periods may be needed for the effect of previous treatment to extinguish, and the effect of new treatment to commence and stabilize. Insufficient length of either might confound estimation of long-term treatment effect | Negligible or modest duration for onset and carryover (e.g., short-acting psychostimulants for ADHD) allows single-patient trials to provide valid knowledge about long-term treatment effect, especially when accompanied with appropriate washout or analytic strategies to untangle slow onset and carryover effects from long-term treatment effect | Long duration of onset and/or carryover (e.g., long-acting medications) |
| Lack of adequate evidence | Existing clinical evidence not adequate to inform treatment decision for individual patients | Lack of adequate evidence creates the need for evidence to be gleaned from single-patient trials (e.g., effectiveness of prophylactic antibiotics in spinal cord injury patients with frequent urinary tract infections) | Adequate evidence: there is no need for further evidence from single-patient trials (e.g., effectiveness of HMG-CoA reductase inhibitors [statins] for reduction of cardiovascular risk in individuals with established coronary artery disease) |
Abbreviation: ADHD, attention-deficit hyperactivity disorder.
a
The assumption of stable treatment effect is weaker than the assumption of stable treatment outcome under both treatments. With the assumption of stable treatment effect, it is possible for treatment outcome to manifest a time trend, say, a gradual deterioration over time, as long as the trajectories are parallel for the two treatments, so that the difference between the treatments remains constant (stable). In other words, this assumption amounts to a requirement that treatment effect and time trend are additive, that is, there is no treatment × time interaction.