The impact of the ambiguous definition of “month” on pharmacotherapy

Abstract Aim The Gregorian calendar divides a common year into 12 months of irregular length. As a result, whenever time is measured in months, an unavoidable degree of inaccuracy exists. We hypothesize that the use of this unprecise measure of time has profound implications for the field of pharmacotherapy from practical and drug safety issues, to variations in drug budgets, and pharmacoepidemiological, industrial and drug regulatory considerations, such as price-fixing policies. In this paper, we have tried to gather evidence in favor of our hypothesis, focusing on the particular case of antipsychotics. Methods First, we examined all monthly prescriptions of long acting injectable aripiprazole or paliperidone in the Basque Country from January 1st to December 31st, 2017. Second, we investigated how the WHO Collaborating Centre for Drug Statistics defines the defined daily dose (DDD) for these drugs. Third, we analyzed the pack size of oral solid formulations of antipsychotics on the market in Spain. Finally, we explored how evidence from clinical trials is transferred to clinical practice and how it may affect drug fixing-policies. Results We found that “monthly” and “every 4 week” injections were prescribed for approximately half of patients. We estimated that an extra cost of almost half a million euros (€495,420) would have been incurred if all prescriptions had been every 4 weeks. We also found that 21 additional adverse site reactions per year could be expected for aripiprazole. Besides, the WHO Collaborating Centre for Drug Statistics calculates the defined daily dose using a 30-day interval for these drugs. In addition, we found that pack sizes for currently available solid oral antipsychotic formulations are inconsistent, with 53% being sold as 28-day multiples and 46% as 30-day multiples. Finally, we found out that although the vast majority of clinical trials are performed in weeks, drug regulatory agencies frequently use the term “month” or “monthly” in the summary of product characteristics of marketed antipsychotics. Conclusion This study shows that the inconsistent definition of month has deep implications on various aspects of pharmacotherapy. Considering all the data given above, we urge drug regulatory agencies to specifically avoid the term “month” in the summary of product characteristics and adopt 4-week intervals instead. We also suggest that the WHO Collaborating Centre for Drug Statistics establishes a new 28-day based DDD for “monthly” antipsychotics. Finally, healthcare providers worldwide should abstain from using “monthly” frequencies in drug prescription software tools.