A sequential parallel comparison design (SPCD) trial involves two double-blind stages of treatment, with Stage 2 commencing immediately at the conclusion of Stage 1. Ideally, neither patients nor investigators are aware of when Stage 1 ends and Stage 2 begins and ends. The patients who are identified as placebo nonresponders (PNRs) during Stage 1 are re-randomized in Stage 2 and included in the primary efficacy analysis set, along with all patients from Stage 1.
Therefore, SPCD represents a partial enrichment for PNRs. Patients on active drug or placebo responders from Stage 1 continue in Stage 2 and contribute to the safety and tolerability analysis.
Stage 1 of a SPCD Trial
- Compares drug and placebo in all patients, as in a conventionally designed parallel arm trial, with the expectation of a higher placebo response
- Generates a cohort of PNRs
Stage 2 of a SPCD Trial
Stage 2 compares drug and placebo among the re-randomized PNRs from Stage 1, thus allowing the measurement of a therapeutic signal against a significantly reduced placebo response.
Please note that we refer to the investigational treatment as "drug," but such treatment can also be a medical device or other type of therapy, as long as the two-stage study design applies and blinding, as well as operational integrity, can be ensured.