Currently most sponsors perform randomization using an Interactive Voice Response System (IVRS) so that treatment codes for individual patients are no longer available at the sites for inspection.
The IVRS utilizes a dynamic randomization system using an adaptive minimization technique for pre-specified stratification variables. The randomization algorithm evaluates previous treatment assignments across the different strata to determine the probability of treatment assignment. There are no fixed randomization lists available prior to enrollment of patients and there are no pre-determined randomization schedules. The randomization algorithm is the source document and is supposed to be signed and dated prior to the time when the first patient is randomized into the study. An external vendor is used to manage the treatment allocation codes. Once a subject is found to be eligible for a trial, the investigator contacts the IVRS vendor and provides details about the subject including their stratification factors. Typically sites receive confirmation faxes from the IVRS vendor that include relevant patient information such as the date of randomization, the date of last visit and the date the last medication was assigned.
In emergences, investigators must call the IVRS vendor to break the treatment code since there are no longer envelopes with patient numbers and treatment codes for investigators to open at the sites. Treatment codes may be released to external vendors prior to the final analysis in order for plasma concentration analyses or PK modeling to be performed in patients receiving the new investigational treatment. Treatment codes may also be released or partially broken up to the code level (e.g. treatment A, B) for the Data Safety Monitoring Board (DSMB) and may be completely unblinded if the chairman of the DSMB requests it. Treatment codes are released to the sponsor or contract research organization after the official analysis database lock.
Nowadays, the IVRS moves to the web-based system. The term is also becoming IWRS (interactive web response system). It could be the situation, when we use the term IVRS, it actually means IWRS.
The utility of the IVRS/IWRS is not just limited to the randomization. It can be used in other areas as well:
- Collecting the clinical efficacy outcome. For example, in IBS (Irritable Bowel Syndrome) study, the IVRS is used to collect the information about the presence or intensity of several IBS related symptoms daily (such as satisfactory relief, Abdominal discomfort or pain, Bloating, Stool frequency, Stool consistency...)
- Patient Reported Outcome (ePRO)
- Outcome research
- Cohort management (open/close a cohort) in dose-escalation studies
- Patient registry / registry studies
- Drug supply managment / Study drug inventory tracking