Blinding and randomization

A Norwegian pharmaceutical preparation company, Kragerø Tablettproduksjon, over-encapsulated the medicine used in the study. They used gelatin capsules where red iron oxide was used for color and titanium oxide as an opacifier. The final product was tested before the trial started to ensure that the capsules had the same look, feel, weight, and taste. The study medicine was packed in 2 different kits, one with 9 capsules containing 200 mg pivmecillinam each, the other with 9 capsules containing 600 mg ibuprofen each. Each kit was labeled with a study number. The labeling was done following a computer-generated randomization list created by an independent statistician using randomized block sizes of 2, 4, 6, or 8, stratified by country [16]. Different study numbers were assigned to each study site: Oslo, 1000–1299; Bergen, 1300–1399; Denmark, 1400–1499; and Sweden, 1500–1599. The list linking the study number to the active substance was kept at Kragerø Tablettproduksjon. The list was retrieved only at the end of the study, when all data had been collected and entered into the study database, and the SAP was completed and signed.

Following the randomization list, Kragerø Tablettproduksjon distributed the study medicine to each study site, where it was kept in a locked facility. At inclusion, each patient received a kit labeled only with the study number. Neither the research nurse/doctor nor the patient knew which active substance was given, thus resulting in blinding for both the nurse/doctor and patient.