A randomized controlled trial of the ketogenic diet in refractory childhood epilepsy
We would like to thank Drs. Hansashree Padmanabha, Dr. Renu Suthar, and Dr. Naveen Sankhyan for their interest in our article.1
More information about the randomization procedure and the intervention (treatment with the ketogenic diet) is published in the design article in 2011.2 The diet was introduced and monitored (including compliance assessment) according to the Dutch guideline for KD.3 Ketosis which indicates compliance was measured at time points T0, T2, and T3. At home, urine ketone levels were checked daily, and if it was impossible to obtain urine samples, beta‐hydroxybutyrate was measured by finger‐prick three times a week. We have referred to this article and the guideline because of the limited number of words that could be used in the article.
As mentioned in Table 1, 57.1% of the patients in the ketogenic diet group had daily or almost daily seizures, compared to 59.1% in the care as usual group (CAU). Only one patient in the ketogenic diet group had <1 seizure a month and none in the CAU group. In our opinion, a baseline of 1 month is justified. Two previously published RCTs on the ketogenic diet used a 4‐week baseline period.5 Choosing a similar design made it easier to compare the results.
We have not used the terminology superiority, equivalence, or non‐inferiority. These terms are used in anti‐epileptic drug (AED) trials because regulatory authorities require proof of efficacy before a license can be granted to a new AED, comparing the new drug with the standard AED (or established treatment). In our opinion, it is not applicable in treatment with a diet with evidence for efficacy from clinical studies.
We fully agree with the definition of an ITT analysis which means including all patients after randomization for analysis irrespective of their compliance, the group which they were randomized in or any protocol deviation.7 In retrospect, the term modified ITT analysis would have been more appropriate. Modified ITT allows the exclusion of some randomized subjects in a justified way.7 In our study, designed as a cost‐effectiveness study of the ketogenic diet, we have used post‐baseline assessment.8 A dropout was defined as a child who drops out of the study before the first consultation with the neurologist, which was scheduled 6 weeks after either initiating the KD or after randomization to care as usual. Dropouts identified by this definition were replaced by other eligible participants.1
It is a good suggestion for future work to present all P‐values mentioned in the text, also in the tables and/or abstract.