Efficacy and safety of betahistine treatment in patients with Meniere’s disease: primary results of a long term, multicentre, double blind, randomised, placebo controlled, dose defining trial (BEMED trial)
We are unclear how the primary outcome was defined in this trial--specifically, whether it is a rate or a count, and how missing data were handled.
The publication in The BMJ defines the primary outcome as a rate "The primary efficacy outcome was the individual attack rate standardised on a 30 day interval (starting from timepoint 1—defined as the date of first intake, with the day of first study drug intake being day 1). The number of evaluated days was defined as the number of days with non-missing information about the patient’s vertigo status, as provided by the daily diary recordings. For example, a patient with 12 attacks during 75 documented days (that is, 75÷30=2.5 intervals) has the rate 12÷2.5=4.8. The 15 undocumented days out of the prespecified 90 day assessment period (starting day 181, ending day 270) were considered as missing at random." [1]
However the protocol [2], and two registry entries [3] [4] define the primary outcome as a count, e.g. the protocol states: "Primary efficacy endpoint is the number of vertigo attacks in the three treatment arms during the last three months of the nine months treatment period." [2]
Could the authors clarify this point, as the two methods would seem to treat missing data differently?
Rapid Response:
Question about primary outcome definition
We are unclear how the primary outcome was defined in this trial--specifically, whether it is a rate or a count, and how missing data were handled.
The publication in The BMJ defines the primary outcome as a rate "The primary efficacy outcome was the individual attack rate standardised on a 30 day interval (starting from timepoint 1—defined as the date of first intake, with the day of first study drug intake being day 1). The number of evaluated days was defined as the number of days with non-missing information about the patient’s vertigo status, as provided by the daily diary recordings. For example, a patient with 12 attacks during 75 documented days (that is, 75÷30=2.5 intervals) has the rate 12÷2.5=4.8. The 15 undocumented days out of the prespecified 90 day assessment period (starting day 181, ending day 270) were considered as missing at random." [1]
However the protocol [2], and two registry entries [3] [4] define the primary outcome as a count, e.g. the protocol states: "Primary efficacy endpoint is the number of vertigo attacks in the three treatment arms during the last three months of the nine months treatment period." [2]
Could the authors clarify this point, as the two methods would seem to treat missing data differently?
References
[1] http://www.bmj.com/content/352/bmj.h6816
[2] http://www.bmj.com/content/bmj/suppl/2016/01/21/bmj.h6816.DC1/adrc027003...
[3] http://www.isrctn.com/ISRCTN44359668?link_type=ISRCTN&access_num=ISRCTN4...
[4] https://www.clinicaltrialsregister.eu/ctr-search/trial/2005-000752-32/DE
Competing interests: Peter Doshi is an associate editor at The BMJ.