Article type
Year
Abstract
Background:
Classical randomized controlled trials often meet difficulties in enrolment and compliance due to subjects’ preference for the randomization scheme. Zelen’s design can largely resolve these issues through randomizing subjects before the informing stage.
Objectives:
This study systematically reviewed the progress of Zelen’s design and its modifications in clinical research and clarified its methodological elements, advantages, and limitations.
Methods:
A systematic literature search was conducted for Zelen’s design from the inception of databases (PubMed, Cochrane library, Chinese National Knowledge Infrastructure database, WanFang, and Vip Chinese Science and Technology Journals database) to February 2023. The data were extracted, including sample size, population characters, length of followup, Zelen’s model, group shifting, and statistical methods.
Results:
One hundred and two trials were included. The range in sample size was from 15 to 23,024. The longest follow-up was 17.2 years. The dominant disease in this design was mental disorders (18, 17.65%), followed by osteoarthrosis diseases (15, 14.71%), cancer (10, 9.80%), cardiovascular diseases (9, 8.82%), and others. Regarding types of consent, more than half of the trials used a double-consent (56, 54.90%), 36 (35.30%%) used a single-consent, and others (10, 9.80%) did not report the consent procedure. Twelve trials (11.76%) used a modified Zelen’s design nested within an observational study. This design used a two-stage informed consent. Stage 1, patients were invited to participate in a cohort study; Stage 2, patients randomized in the experimental group were informed of the allocation result and asked whether they would like to follow the treatment. Five trials used the McNulty-Zelen design, which could be applied in cluster randomized controlled trials and overcome the potential bias of the Hawthorne effect, e.g., trials involving educational interventions. Informed consent was obtained from a third party on behalf of the participants. Intention-to-treat analysis was the main population used in Zelen’s design.
Conclusions:
Zelen’s design has a broad application in the foreground in clinical trials. It could also be used to adapt to research needs by combining with various observational studies.
Patient or healthcare consumer involvement: No patients or consumers participated in research activities.
Classical randomized controlled trials often meet difficulties in enrolment and compliance due to subjects’ preference for the randomization scheme. Zelen’s design can largely resolve these issues through randomizing subjects before the informing stage.
Objectives:
This study systematically reviewed the progress of Zelen’s design and its modifications in clinical research and clarified its methodological elements, advantages, and limitations.
Methods:
A systematic literature search was conducted for Zelen’s design from the inception of databases (PubMed, Cochrane library, Chinese National Knowledge Infrastructure database, WanFang, and Vip Chinese Science and Technology Journals database) to February 2023. The data were extracted, including sample size, population characters, length of followup, Zelen’s model, group shifting, and statistical methods.
Results:
One hundred and two trials were included. The range in sample size was from 15 to 23,024. The longest follow-up was 17.2 years. The dominant disease in this design was mental disorders (18, 17.65%), followed by osteoarthrosis diseases (15, 14.71%), cancer (10, 9.80%), cardiovascular diseases (9, 8.82%), and others. Regarding types of consent, more than half of the trials used a double-consent (56, 54.90%), 36 (35.30%%) used a single-consent, and others (10, 9.80%) did not report the consent procedure. Twelve trials (11.76%) used a modified Zelen’s design nested within an observational study. This design used a two-stage informed consent. Stage 1, patients were invited to participate in a cohort study; Stage 2, patients randomized in the experimental group were informed of the allocation result and asked whether they would like to follow the treatment. Five trials used the McNulty-Zelen design, which could be applied in cluster randomized controlled trials and overcome the potential bias of the Hawthorne effect, e.g., trials involving educational interventions. Informed consent was obtained from a third party on behalf of the participants. Intention-to-treat analysis was the main population used in Zelen’s design.
Conclusions:
Zelen’s design has a broad application in the foreground in clinical trials. It could also be used to adapt to research needs by combining with various observational studies.
Patient or healthcare consumer involvement: No patients or consumers participated in research activities.