Background: Since random treatment allocation is hardly understood by the majority of patients, a new 'nested consent design' for clinical trials is proposed.
Proposed design: The design consists of a two-step enrollment of study subjects. The first step is the enrollment of participants into a follow-up study, where consent to be subjects involved in the follow-up is obtained. The second step is the enrollment of randomly sampled eligible participants into a new treatment group. After the explanation of (1) treatment mode, (2) additional burdens associated with the proposed treatment and (3) expected effects and possible adverse events, written informed consent is obtained. Those who reject participation and those who are not allocated into the new treatment are treated by standard care. Endpoints are set to be the same for all follow-up study participants whether allocated into the new treatment or not, and follow-up is carried out in the same manner. Analyses are performed between those allocated to the new treatment and those non-allocated on an intent-to-treat basis.
Example: Although not a clinical trial, this design was applied in a smoking cessation program at Aichi Cancer Center Hospital for first-visit patients who answered in a questionnaire survey that they were smokers. Out of 1330 necessary participants, 324 were enrolled in the follow-up study during the first three months of enrollment.
Conclusions: The design was found to be feasible for prevention trials, and possibly for clinical trials to compare a new treatment with a standard treatment. There seems to be no ethical difference between this design and the one-arm study design.