SPIRIT Statement (Standard Protocol items) for n-of-1 trials

The SPIRIT Extension for N-of-1 Trials (SPENT 2019) provides guidance for developing complete, transparent and high-quality protocols for N-of-1 trials. Building on the SPIRIT Statement for interventional trial protocols, it introduces additional protocol items and detailed explanations that address the methodological features unique to individualized crossover trials. The guideline is intended to improve protocol quality, facilitate reproducibility, and promote consistent design and reporting of N-of-1 studies.

For protocol development, the guideline provides recommendations on defining eligibility criteria, specifying treatment periods and treatment sequences, randomisation procedures, blinding, washout periods, outcome selection, timing and frequency of outcome assessment, statistical analysis, data collection, and interpretation of individual treatment effects. It also highlights practical considerations for participant involvement, adherence, protocol deviations, and transparent documentation of methodological decisions. These recommendations help ensure that N-of-1 trial protocols are scientifically rigorous and sufficiently detailed to support implementation and interpretation.

Although N-of-1 trials are not appropriate for every rare disease, they can provide valuable evidence when evaluating symptomatic treatments, chronic stable conditions, or individualized therapeutic responses in very small populations. Researchers considering this design can use the SPENT guideline to develop robust protocols that align with international standards for protocol content and reporting while maximising the quality and interpretability of individual patient evidence.