Single-patient drug trial methodology for allergic rhinitis

Abstract

Background: Historically, single-patient trials (SPTs) have been specifically designed for each patient, requiring significant time and effort for execution. There has been no previous attempt to standardize an SPT for routine commercial availability.

Objective: To validate the use of an SPT method to discriminate effectiveness and adverse events while comparing drugs/doses in patients with allergic rhinitis.

Design: Double-blind, randomized, 4 paired-period, multiple-crossover SPT.

Setting: Academic and commercial investigative sites.

Patients: Thirty-six patients with allergic rhinitis were evaluated for the most appropriate treatment; 6 of these participated in 2 different SPTs.

Interventions: Treatment of symptoms of allergic rhinitis by comparing either loratadine with chlorpheniramine maleate or loratadine with placebo in a series of SPTs.

Measurements: Effectiveness endpoints were selected from a modern, Food and Drug Administration (FDA)-approved new drug application. Expected adverse events were directly solicited; unsolicited events were also recorded. Total signs and symptoms cumulatively included sneezing, runny nose, itchy nose, teary eyes, and itchy eyes. Quality of life was measured by the most bothersome symptom and the patient's global evaluation.

Results: Of 42 initiated SPTs, 40 (95%) provided complete data and 1 (2%) provided partial data, resulting in 41 (98%) evaluable tests. Thirty-one evaluable SPTs compared loratadine 10 mg/d with chlorpheniramine maleate 12 mg twice daily, and 10 SPTs compared loratadine 10 mg/d with placebo. Four of 31 SPTs (13%) showed significant superiority for loratadine over chlorpheniramine maleate and 5 of 31 (16%) for chlorpheniramine maleate over loratadine. Twenty-two of 31 (71%) showed parity performance between loratadine and chlorpheniramine maleate. Loratadine was significantly superior to placebo in 3 of 10 trials (30%), consistent with rates found in 3 pivotal group trials used for FDA approval (24%, 17%, and 0%). Sleepiness could be discriminated for loratadine versus placebo and for chlorpheniramine maleate versus loratadine.

Conclusions: The allergic rhinitis SPT proved to be acceptable to patients, feasible to administer, and reproducible. It can statistically discriminate effectiveness and adverse events, serving as a useful, prognostic tool in community practice.