A number needed to treat, or NNT, of three does not mean that exactly one in every three new patients will be cured. In a 2023 secondary report of a dextroamphetamine patch trial, the NNT summarized the difference between active and placebo response proportions after participants had already undergone open-label dose optimization.
Selection happened before the blinded comparison
The underlying trial enrolled children and adolescents aged 6–17 years with ADHD. Of 110 entering the five-week open-label optimization phase, 106 were randomized into a two-week, double-blind crossover comparison. Each participant received the optimized active patch and placebo in different treatment periods.
The research used nominal patch doses of 5, 10, 15 and 20 mg, corresponding to labeled delivery doses of 4.5, 9, 13.5 and 18 mg over nine hours. Patch content, delivered dose, oral dose and a measured blood concentration are different quantities. Those numbers should stay attached to their formulation and wear interval.
Because optimization preceded randomization, the blinded comparison concerned people who had reached that stage. It was not a blinded first-treatment comparison in all potential users. This distinction matters for both benefit and tolerability.
The NNT depended on the response definition
The authors calculated NNT post hoc as the inverse of the active-minus-placebo response proportion. Among 104 participants with ADHD Rating Scale IV assessments from both periods, remission, defined as a score of 18 or less, occurred during active treatment in 73/104 and during placebo in 24/104. The reported NNT was three.
For at least a 50% symptom-score reduction, the corresponding counts were 71/104 and 25/104, again giving a reported NNT of three. These endpoints are not interchangeable: reaching a low final score and improving by a specified percentage depend differently on the starting score.
The global-improvement endpoint counted participants rated much or very much improved. Its proportions were 89/104 during active treatment and 25/105 during placebo, producing a reported NNT of two. Those denominators differ from the paired symptom-scale sample and should not be silently replaced by 106.
One participant contributed to both treatment conditions
This was a crossover, not two independent parallel groups. The symptom responder comparisons used the McNemar test for paired data. The active and placebo totals describe conditions experienced by overlapping participants; they do not identify a fixed fraction of people who can benefit only from the drug.
The NNT is also tied to these endpoints, study duration and selected population. It cannot be transferred unchanged to another age group, dose, treatment interval, clinical setting or comparator. Comparing this number with an NNT from an unrelated trial does not establish comparative superiority.
Benefit alone is not the full benefit–harm calculation
The report did not calculate number needed to harm or likelihood of being helped versus harmed. During open-label optimization, 105/110 participants reported treatment-emergent adverse events, mostly mild or moderate; three discontinued because of such events. No treatment-emergent-event discontinuations occurred during the blinded phase.
The later absence of discontinuations cannot erase the earlier events or establish absence of harm for a newly treated patient. The authors specifically recognized that the open-label lead-in complicated a complete benefit–harm calculation. They also noted short duration, the artificial classroom setting and the lack of a carryover assessment for the secondary endpoints.
What the report adds
The secondary results document symptom and parent-rating benefits in the studied group, while making the chosen response thresholds visible. This is a further analysis of the pivotal trial, not an independent replication. It supports an endpoint-specific description of benefit; it does not supply a universal probability of cure, a safety guarantee or an impairment rule based on drug detection.
Source
Cutler AJ, Suzuki K, Starling B, et al. d-Amphetamine transdermal system in treatment of children and adolescents with attention-deficit/hyperactivity disorder: secondary endpoint results and post hoc effect size analyses from a pivotal trial. Journal of Child and Adolescent Psychopharmacology. 2023;33(5):176–182. doi:10.1089/cap.2023.0005. Historical secondary report of trial NCT01711021.
Leave a Reply