The main issue in this study is the use of an n of 1 trial for the evaluation of treatments for nausea and vomiting in pregnancy. These trials are used to decide what treatment benefits an individual patient and are a more scientific method of decision making than the usual method used by general practitioners: asking the patient to return if the first treatment doesn't work and trying a second one.1 As I have pointed out before, R A Fisher, one of the greatest statisticians, discussed at length an n of 1 trial investigating whether a woman could tell whether milk was added before or after the tea,2 and this has even become the title of a book.3 They are usually used in chronic illness, such as arthritis, to evaluate the best long term treatment for a patient. A recent good example showed that paracetemol may be used instead of non-steroidal anti-inflammatory drugs in some patients with osteoarthritis.4
However it is worth mentioning a few problems associated with n of 1 trials.5 In terms of design an investigator needs to decide:
How many treatment periods
How long to treat within each period.
Since nausea in pregnancy obviously has a limited duration, few treatment periods will be available, and a compromise will have to be made about the number of periods compared with the length of each one. The trial had only five pairs of treatment periods, and so did not have much power to detect an effect unless it was large. However, that is what we would be hoping for in this case. To accommodate even five pairs of treatment periods within the time span, the treatment was given for only two days, and several respondents commented that two days of active treatment is unlikely to be enough to correct a vitamin deficiency.
N of 1 trials are crossover trials, and like crossover trials they are also vulnerable to carry over effects, where the effect of treatment extends to the next treatment period. This may be a problem in this case, because if the treatment did in fact cure the deficiency, it is unlikely to reappear again after two days.
An interesting problem (discussed at length by statisticians since it affects the P value) is what Ms Reynolds knew of the allocation. Was she simply told that she was going to be treated for 25 days with either vitamin B-6 or placebo allocated at random or did she know that there were five matched periods? Despite these caveats, it would be nice to see more general practitioners conducting these type of trials.
Competing interests: None declared.
References
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