Author: toxlaw

Two stimulant studies can report different remission percentages even if their treatments are not meaningfully different. Before comparing the numbers, determine whether “remission” meant the same thing.

The mixed-salts reanalysis

Adler and colleagues reported post hoc analyses from two adult ADHD trials of oral SHP465 mixed amphetamine salts extended release. One used dose optimization over seven weeks, 12.5–75 mg; the other used fixed doses of 25, 50 or 75 mg over six weeks.

The intention-to-treat populations were 268 in the optimization study, comprising 136 active and 132 placebo participants, and 405 in the fixed-dose study, comprising 302 active and 103 placebo participants. These were reanalyses of existing trials, not newly recruited replication cohorts.

Several response definitions were examined

The authors considered a 30% symptom-score reduction plus clinician improvement, a stricter 50% reduction plus clinician improvement, and an absolute ADHD rating score of 18 or less. Remission, however, required a score of 12 or less.

At the final treatment week, the remission criterion was met by 37.2% receiving mixed salts versus 19.7% placebo in the optimization study. Corresponding fixed-dose percentages were 39.7% and 10.0%. These are percentages under a particular threshold and observation rule.

Why a lisdexamfetamine percentage is not directly comparable

A separate 2013 lisdexamfetamine analysis defined symptomatic remission as a score of 18 or less. The same score that counted as remission there was treated as one response definition in the mixed-salts report.

A stricter cutoff generally classifies fewer observations as meeting the target. Thus a lower reported remission rate cannot automatically establish inferior pharmacologic efficacy. Different populations, doses, trial lengths and missing-data handling add further obstacles to comparison.

Final week and endpoint also differ

The mixed-salts report distinguished the final treatment week from endpoint, which could include earlier termination. Remission percentages at endpoint were lower than the final-week figures. Quoting one study’s final-week percentage against another study’s last-observation percentage creates another mismatch.

Time-to-event analyses also answer a different question from maintaining remission at every later visit. Their nominal significance does not establish permanent recovery.

How to use these findings

The post hoc analyses support symptom improvement over placebo under several definitions. They do not create a universal remission standard, validate cross-trial treatment rankings or establish normal work and driving performance.

Any comparison should specify the scale, cutoff, required change, denominator and timing. The secondary lisdexamfetamine source used for the definition comparison is Mattingly et al., BMC Psychiatry 2013;13:39, doi:10.1186/1471-244X-13-39. Both reports are historical research, not current prescribing guidance.

Scientific source

Adler LA, Robertson B, Chen J, Sarkis E. Post hoc Responder and Remission Analyses from Two Studies of SHP465 Mixed Amphetamine Salts Extended-Release Among Adults with Attention-Deficit/Hyperactivity Disorder. Journal of Child and Adolescent Psychopharmacology. 2020;30:427–438. doi:10.1089/cap.2020.0012. Original commentary on the supplied paper.

Evidence about a stimulant must retain the formulation and dose tested. A 2020 trial of low-dose SHP465 mixed amphetamine salts found no significant advantage over placebo, despite positive studies using other regimens.

The actual exposure

The randomized double-blind trial tested oral SHP465 mixed amphetamine salts extended release, 6.25 mg once daily, for four weeks in children aged 6–12 with ADHD. This dose refers to the specified mixed-salts product, not methamphetamine or an interchangeable amount of every amphetamine formulation.

Eighty-nine children were randomized: 45 active treatment and 44 placebo. One placebo participant received no medication. The safety set therefore contained 88 participants, the full analysis set 87 and the completed-study population 83.

The primary result was null

The primary outcome was change in the ADHD Rating Scale, fifth edition, child home version. At week four, the least-squares mean treatment difference was −1.9 points, with a 95% confidence interval from −6.8 to 3.1; p = 0.451.

The clinician global-improvement comparison was also nonsignificant: −0.1 points, 95% confidence interval −0.5 to 0.3. Exploratory age-subgroup analyses did not establish superiority either. The data therefore did not demonstrate efficacy of this regimen under the trial conditions.

What does a null comparison leave open?

Failure to establish a difference is not proof of precisely zero effect. The confidence interval includes both improvement and a difference favoring placebo. The result also cannot establish that higher doses work, even though other studies may address that separate question.

Likewise, a positive study of another dose cannot erase this null trial. Combining the evidence requires retaining dose, population and outcome rather than reporting only the favorable experiments.

Safety was a separate outcome

Treatment-emergent adverse events were reported by 24.4% of active recipients and 16.3% of placebo recipients. Headache and appetite reduction occurred, and vital signs were monitored.

The short study and modest sample do not establish absence of uncommon or long-term adverse effects. “Well tolerated” in the authors’ discussion should not become a claim that low-dose exposure is harmless for every child.

The appropriate historical conclusion

This trial did not establish a four-week symptom benefit from 6.25 mg/day of this extended-release product in its selected pediatric ADHD population. It did not measure drug concentrations, driving or functional impairment from illicit methamphetamine.

The study is useful precisely because it supplies a controlled null finding. It supports careful dose-specific interpretation, not a prescribing instruction to increase treatment or a blanket conclusion about the stimulant class.

Scientific source

Mattingly G, Arnold V, Yan B, Yu M, Robertson B. A Phase 3, Randomized Double-Blind Study of the Efficacy and Safety of Low-Dose SHP465 Mixed Amphetamine Salts Extended-Release in Children with Attention-Deficit/Hyperactivity Disorder. Journal of Child and Adolescent Psychopharmacology. 2020;30:549–557. doi:10.1089/cap.2020.0005. Original commentary on the supplied paper.

Two treatments may look similar under one outcome definition and different under another. A 2011 reanalysis comparing lisdexamfetamine with mixed amphetamine salts illustrates how changing a response threshold changes the scientific question.

The original comparison

Fifty-two children aged 6–12 entered a crossover classroom study, and 50 completed it. An open-label period first optimized mixed amphetamine salts extended release at 10, 20 or 30 mg/day. Children then received that formulation, approximately corresponding lisdexamfetamine doses and placebo during randomized blinded periods.

These were repeated observations in the same children. They were not three independent groups of 50. The optimization procedure also selected doses using one active formulation before the comparison.

What did the primary outcome show?

Both active treatments improved classroom deportment relative to placebo. The original primary efficacy comparison did not establish a difference between the two active treatments. Their mean deportment scores were similar.

The later report examined clinician global-improvement ratings. Combining “very much improved” and “much improved” produced response percentages of 74% with lisdexamfetamine, 72% with mixed salts and 18% with placebo.

What happened with a stricter threshold?

The post hoc analysis isolated “very much improved,” the highest improvement category. Sixteen of 50 children, 32%, met that threshold on lisdexamfetamine, compared with eight, 16%, on mixed salts.

Ten children met it only with lisdexamfetamine, two only with mixed salts, six with both and 32 with neither. The paired McNemar comparison was p = 0.0386. The discordant pairs, rather than treating all observations as independent, determine that test.

What does this difference mean?

It supports a difference under this particular post hoc clinician-rating threshold in this small crossover sample. It does not overturn the null active-treatment comparison on the original primary classroom outcome.

The category boundary was examined after reviewing the data. Multiple possible outcomes and thresholds increase the importance of replication and prospective specification. Approximately equivalent dosing also does not make the formulations pharmacokinetically identical.

Why not declare one medicine generally superior?

Different measures captured different aspects and times of improvement. A single global rating and repeated classroom observations are not interchangeable. Small sample size, short periods, prior dose optimization and industry involvement further limit broad conclusions.

For interpretation, state the exact threshold and design: a post hoc difference in the highest clinician-improvement category, not universal superiority across all outcomes. The study provides no individual impairment or driving-safety determination.

Scientific source

López FA, Scheckner B, Childress AC. Physician perception of clinical improvement in children with attention-deficit/hyperactivity disorder: a post hoc comparison of lisdexamfetamine dimesylate and mixed amphetamine salts extended release in a crossover analog classroom study. Neuropsychiatric Disease and Treatment. 2011;7:267–273. doi:10.2147/NDT.S17002. Original commentary on the supplied paper.

Charts showing different averages across age or sex groups can invite conclusions that the investigators never formally tested. A lisdexamfetamine item-level analysis deliberately used descriptive presentation, making that boundary central to its interpretation.

What data were reanalyzed?

Weisler and colleagues examined two previously reported four-week randomized placebo-controlled trials: one in children aged 6–12 and another in adults aged 18–55. These were secondary analyses of existing trials, not new participants or independent replications.

The analysis grouped participants by age bands and sex and examined individual items on the ADHD Rating Scale IV. Adult ratings used prompts intended to capture adult manifestations of symptoms. The original studies used oral lisdexamfetamine doses of 30, 50 or 70 mg/day.

What did the descriptive patterns suggest?

Baseline symptom-item means were generally numerically similar across age-by-sex subgroups. Inattention item scores tended to exceed hyperactivity/impulsivity scores in older participants. Mean endpoint scores were lower after active treatment across the displayed subgroups.

Those observations describe the plotted data. They do not quantify a statistically established treatment-by-age or treatment-by-sex interaction. A numerical difference alone cannot establish that one subgroup responds more strongly.

Why did the authors avoid a comparative test?

The paper expressly chose descriptive presentation rather than comparative statistical analysis. Subgroup composition, sample limitations and the exploratory purpose influenced that decision. The absence of a formal test also means the analysis did not demonstrate equivalence between subgroups.

A phrase such as “regardless of age or sex” must therefore be understood as a description of broadly similar observed patterns, not proof that demographic characteristics never modify response.

The recruitment criteria matter

The pediatric trial excluded predominantly inattentive ADHD presentations. That selection can influence apparent sex differences because the sample does not include the full distribution of symptom presentations seen clinically.

Adults and children were also drawn from separate trials with different rating contexts. Comparing their averages is not a longitudinal study showing how the same people’s symptoms evolve with age. Endpoint included early termination, rather than exclusively complete four-week follow-up.

What is the defensible use of this evidence?

The report helps identify questions about symptom composition and shows why total scores can conceal item-level patterns. It does not establish a demographic rule for prescribing, a biological explanation for sex differences or a universal amphetamine-response profile.

This historical, exploratory reanalysis should accompany, rather than replace, the original randomized trial results. It also provides no individual measurement of intoxication, functional incapacity or driving performance.

Scientific source

Weisler RH, Adler LA, Kollins SH, et al. Analysis of individual items on the attention-deficit/hyperactivity disorder symptom rating scale in children and adults: the effects of age and sex in pivotal trials of lisdexamfetamine dimesylate. Neuropsychiatric Disease and Treatment. 2014;10. doi:10.2147/NDT.S47087. Original commentary on the supplied paper.

A large treatment-response percentage can sound like a cure rate when its definition and denominator are omitted. Mattingly and colleagues’ 2013 analyses show why adult ADHD response, symptomatic remission and maintenance need separate descriptions.

Two studies, different designs

The report reanalyzed a four-week randomized placebo-controlled trial and a subsequent open-label extension. The short trial randomized 420 adults; 414 contributed to efficacy analyses. Oral lisdexamfetamine doses were 30, 50 or 70 mg/day.

The extension enrolled 349 adults, with 345 in its efficacy population. Participants underwent dose optimization followed by maintenance. Extension findings were not an independent placebo-controlled replication of the initial experiment.

The definitions drove the percentages

Clinical response was defined post hoc as at least a 30% reduction on the ADHD rating scale plus a clinician global-improvement rating of one or two. Symptomatic remission meant a total ADHD rating score of 18 or less.

In the short trial, 69.3% receiving lisdexamfetamine met the response definition, compared with 37.1% receiving placebo. Remission percentages were 45.5% and 16.1%, respectively. Neither definition required permanent absence of symptoms or independently demonstrated normal functioning in every setting.

Any-time response is not final-visit response

In the extension, 325 of 345 met response criteria at some point, while 286 met remission criteria at some point. At the final visit, including early termination, the corresponding numbers were 285 and 227.

A participant can meet a threshold once and later cease meeting it. An any-time percentage therefore cannot be substituted for an endpoint percentage or a continuous-maintenance percentage.

Maintenance used a selected subgroup

The maintenance analyses excluded participants without evaluable maintenance data. Among those already classified as responders at entry to maintenance, 209 of 278, or 75.2%, did not subsequently lose response under the reported rule. For remission, 140 of 213, or 65.7%, did not lose remission.

These percentages describe selected initial achievers. Reporting them as the percentage of all enrolled adults who remained well for a year would change the denominator and overstate the evidence.

What should remain uncertain?

The definitions were post hoc, the extension was open label, and treatment discontinuation and selection affect interpretation. The analysis establishes symptom-scale patterns under historical research conditions, not permanent recovery or an individual prognosis.

For a client-ready explanation, specify the threshold, observation window and eligible population whenever quoting a percentage. This report does not establish driving safety, work capacity or a current prescribing recommendation.

Scientific source

Mattingly GW, Weisler RH, Young J, et al. Clinical response and symptomatic remission in short- and long-term trials of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder. BMC Psychiatry. 2013;13:39. doi:10.1186/1471-244X-13-39. Original commentary on the supplied paper.

Calling a study setting a workplace does not make every result an employment outcome. A 2010 lisdexamfetamine trial tested adults in a simulated workplace, with a repeated mathematics measure as its principal outcome.

Who reached the controlled comparison?

The study enrolled 142 adults aged 18–55 with ADHD. They received four weeks of open-label oral lisdexamfetamine optimization, 30–70 mg/day, before a randomized two-week crossover comparing optimized medication with placebo.

There were 127 randomized participants, 105 in the intention-to-treat efficacy population and 103 study completers. The controlled efficacy sample was therefore smaller than both the enrolled and randomized populations. Participants with several psychiatric, substance-use or medical conditions were excluded.

What was measured?

The Permanent Product Measure of Performance, or PERMP, used mathematics problems calibrated to ability. The primary outcome combined problems attempted and correct, averaged across postdose sessions. It was not the number of paid work products completed or a supervisor’s evaluation.

Testing occurred before dosing and from two through 14 hours afterward. The placebo-adjusted least-squares mean difference in average total score was 23.4 points, with a 95% confidence interval of 15.6–31.2. Individual postdose comparisons also favored lisdexamfetamine.

What does the time course establish?

The trial demonstrates a group difference at the sampled times under the protocol. It does not prove that every participant benefited continuously, establish the earliest possible onset or show that effects ended at 14 hours.

Neither PERMP improvement nor ADHD symptom improvement establishes a plasma amphetamine threshold. The study did not validate a concentration-based rule for safe work or driving.

Safety denominators differ again

All 142 enrolled participants contributed to the initial safety population. During optimization, 79.6% reported a treatment-emergent adverse event; appetite reduction, dry mouth, headache and insomnia were prominent. Crossover event rates came from smaller treatment-exposed groups.

A lower event frequency after optimization should be interpreted alongside selection, discontinuation and prior exposure. It does not establish that treatment became harmless once participants entered the blinded phase.

Where does the evidence stop?

The short, industry-sponsored crossover supports improved structured task performance in selected adults with ADHD who reached the randomized phase. It does not independently establish improved employment retention, fewer workplace accidents or better performance in every occupation.

The useful forensic distinction is between a measured laboratory function and the real-world function in dispute. Evidence connecting those functions must be assessed rather than assumed from the study setting’s name.

Scientific source

Wigal T, Brams M, Gasior M, et al. Randomized, double-blind, placebo-controlled, crossover study of the efficacy and safety of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder: novel findings using a simulated adult workplace environment design. Behavioral and Brain Functions. 2010;6:34. doi:10.1186/1744-9081-6-34. Original commentary on the supplied paper.

“Better than placebo” and “better than the same morning’s predose score” are different comparisons. A 2009 lisdexamfetamine laboratory-school study reported both, with different late-day results. The distinction helps prevent a time-course finding from becoming an overstated claim about continuous improvement.

How the study was organized

Children aged 6–12 with ADHD first underwent four weeks of open-label oral dose optimization at 30, 50 or 70 mg/day. The trial then used two one-week crossover periods of optimized lisdexamfetamine and placebo.

Of 129 enrolled children, 117 were randomized, 113 entered the intention-to-treat efficacy population and 111 completed the study. Safety observations came from the 129 exposed during optimization. These denominators serve different purposes and should not be interchanged.

The placebo-adjusted result

Classroom observers rated deportment and attention. Children also completed an individualized mathematics task measuring attempted and correct responses. Assessments occurred before dosing and at specified times from 1.5 through 13 hours afterward.

Lisdexamfetamine separated significantly from placebo on the primary deportment scale at all postdose assessments, including 13 hours. Mathematics outcomes also favored treatment at all assessed postdose times. The first sampled time was 1.5 hours; the study did not establish effects before that observation.

The predose comparison

In a post hoc analysis within the lisdexamfetamine condition, deportment improved significantly from predose at earlier observations. At 12 and 13 hours, scores were numerically worse than predose but not significantly different.

The placebo condition worsened from its predose score across the day. Consequently, an active-treatment score can resemble its own predose level and still be better than the placebo score measured at the same late time. These findings are compatible rather than contradictory.

Why the design limits interpretation

The late comparison does not establish a plasma amphetamine concentration, a pharmacokinetic cutoff or a universal 13-hour effect in every child. It reflects group behavior under a structured classroom protocol after dose optimization.

Adverse events were more common during optimization than the crossover phase; decreased appetite and insomnia were prominent. Some participants discontinued before randomization, meaning the crossover sample had already passed a treatment-selection stage.

How to state the conclusion

This historical trial supports placebo-adjusted classroom benefits through the final assessed time in its selected ADHD sample. It does not show that every outcome remained better than predose, that benefits continued after 13 hours or that the same timeline applies to driving. A careful description names the outcome, time and reference condition.

Scientific source

Wigal SB, Kollins SH, Childress AC, Squires L, for the 311 Study Group. A 13-hour laboratory school study of lisdexamfetamine dimesylate in school-aged children with attention-deficit/hyperactivity disorder. Child and Adolescent Psychiatry and Mental Health. 2009;3:17. doi:10.1186/1753-2000-3-17. Original commentary on the supplied paper.

A trial can show a favorable secondary result while failing to establish a benefit on its primary endpoint. Ezard and colleagues’ 2025 methamphetamine-dependence trial illustrates why the observation window must remain attached to the conclusion.

What was tested?

Six Australian outpatient clinics randomized 164 adults with methamphetamine dependence and at least 14 use days in the preceding 28 days. Eighty were assigned lisdexamfetamine and 84 placebo.

The oral regimen involved induction to 250 mg/day, 12 weeks of maintenance and a two-week reduction, followed by follow-up. This was a specialist research regimen, not a dose recommendation or evidence that results from lower-dose ADHD treatment automatically transfer to dependence treatment.

Nine randomized participants never started medication and were excluded from analyses: five assigned lisdexamfetamine and four placebo. The treated analytic population was therefore 155, not all 164 randomized participants.

The primary endpoint

The primary efficacy outcome was methamphetamine-use days in the preceding 28 days at week 13. The adjusted difference was reported as 2.2 days, with a 95% confidence interval from −0.5 to 5.0. The trial did not establish a statistically significant primary-endpoint benefit.

This finding should not be replaced by the statement that the trial proved reduced use at treatment completion. The authors characterized evidence at that endpoint as weak.

The positive result covered another period

Across the whole 12-week maintenance phase, the lisdexamfetamine group reported fewer methamphetamine-use days in total: a difference of 8.8 days, 95% confidence interval 2.7–15.0, p = 0.005.

An accumulated difference across 12 weeks is not the same estimand as use in the final 28 days. Early reductions can contribute to a favorable total even when the final-period comparison is uncertain. Neither result establishes abstinence in every participant.

Retention and safety remain part of the result

Only 57% remained on study medication to the primary endpoint. Low retention reduces precision and raises concern about assumptions used for missing outcomes. The COVID-19 pandemic disrupted recruitment and study procedures, and medication adherence relied substantially on self-report.

Serious adverse events occurred in four lisdexamfetamine recipients, reported as 5%. A treatment-group adverse event is not automatically caused by the drug, but it should not disappear behind a general statement of tolerability.

What does the trial support?

The randomized evidence supports a possible reduction in use during treatment, with uncertainty about sustaining that difference at the primary endpoint. It does not establish a cure, an individual impairment threshold or a prescribing instruction. Primary and secondary outcomes must both remain visible when this study is discussed.

Scientific source

Ezard N, Clifford B, Siefried KJ, et al. Lisdexamfetamine in the treatment of methamphetamine dependence: A randomised, placebo-controlled trial. Addiction. 2025;120:1345–1359. doi:10.1111/add.16730. Original commentary on the supplied paper.

A randomized-withdrawal trial asks whether benefits persist when established treatment continues rather than stops. It does not answer the same question as a trial enrolling previously untreated patients. That distinction is central to a 2014 lisdexamfetamine report on quality of life and functioning.

Selection occurred before randomization

Children and adolescents aged 6–17 first received at least 26 weeks of open-label oral lisdexamfetamine, with dose optimization between 30 and 70 mg/day. The open-label full analysis set contained 262 participants. Many came from an earlier European trial, creating cohort overlap with previous publications.

Only 153 entered the randomized-withdrawal phase: 76 continued their optimized dose and 77 switched to placebo for up to six weeks. The study therefore compared selected participants who had already tolerated and continued treatment, rather than an unselected population beginning amphetamine therapy.

What happened to parent-rated quality of life?

Parents completed CHIP-CE and functional-impairment questionnaires. During withdrawal, significant between-group differences favored continued treatment in the Achievement, Risk Avoidance and Satisfaction domains. The reported effect sizes were 0.696, 0.829 and 0.636, respectively.

The findings were not uniform across every domain and subdomain. Within Resilience and Comfort, significant group differences were limited to particular subdomains. A favorable result in selected domains does not demonstrate preservation of every aspect of health or daily life.

The endpoint was not six complete weeks for everyone

Only 57 continued-treatment participants and 16 placebo participants completed the randomized-withdrawal period. Endpoint included the last valid visit or early termination. Describing all 153 as completing six weeks would substantially misstate follow-up.

Withdrawal after a period of successful treatment is also different from receiving placebo without prior treatment. The design addresses maintenance in an enriched population; it cannot independently identify the optimal starting medicine or predict outcomes for initial nonresponders.

How strong were the statistical claims?

These quality-of-life and functional outcomes were secondary objectives. The reported p values were nominal and not corrected for multiple comparisons. The positive results should therefore retain their exploratory or descriptive qualification across the many domains examined.

The open-label improvements before randomization are less causally secure than the randomized comparison. Expectations, time and selection can contribute during a period without a control group.

Practical interpretation

The historical evidence supports maintenance of selected parent-rated benefits among children and adolescents who reached randomization after prolonged treatment. It does not establish a universal need for indefinite therapy, a safe stopping schedule or individual driving capacity. Those questions were not tested, and the report should not be treated as current prescribing advice.

Scientific source

Banaschewski T, Johnson M, Lecendreux M, et al. Health-Related Quality of Life and Functional Outcomes from a Randomized-Withdrawal Study of Long-Term Lisdexamfetamine Dimesylate Treatment in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder. CNS Drugs. 2014;28:1191–1203. doi:10.1007/s40263-014-0193-z. Original commentary on the supplied paper.

Reducing symptoms and improving daily life are related goals, but they are not the same outcome. A historical lisdexamfetamine trial measured parents’ perceptions of achievement, comfort and functioning separately from the main ADHD symptom assessment.

The randomized comparison

Banaschewski and colleagues analyzed secondary outcomes from a seven-week trial in participants aged 6–17. The study randomized 336 children and adolescents to once-daily oral lisdexamfetamine, placebo or osmotic-release methylphenidate. Lisdexamfetamine doses were optimized at 30, 50 or 70 mg/day; the reference methylphenidate doses were 18, 36 or 54 mg/day.

The full analysis set contained 317 participants: 104 receiving lisdexamfetamine, 106 placebo and 107 methylphenidate. Among this set, 77, 42 and 72 completed the study, respectively. Thus endpoint analyses were not simply a comparison of 317 complete seven-week records.

What did parents rate?

The CHIP-CE parent form measured health-related quality of life. Achievement was the prespecified primary quality-of-life domain. The WFIRS-P assessed functional difficulties in domains including family, school, life skills and social activities.

These were parent-reported scales. Achievement ratings are not independent school transcripts, and a scale labeled risk avoidance is not a road-driving experiment. Each outcome retains the meaning of its questionnaire.

The positive and null findings

Lisdexamfetamine improved the Achievement domain versus placebo, with a reported standardized effect size of 1.280. Risk Avoidance, Resilience and Satisfaction also improved significantly. Comfort did not show a significant placebo-adjusted improvement.

On functional impairment, significant effects were likewise not uniform across domains. For example, the Life Skills comparison did not reach significance for lisdexamfetamine. This prevents summarizing the trial as improvement in every aspect of life.

An effect size is a standardized group difference. It is not the proportion of children whose functioning became normal or the probability of benefit for one patient.

Why comparator and endpoint matter

Methylphenidate served as a reference treatment. Separate comparisons of each medicine with placebo do not establish a statistically tested difference between the active medicines.

Endpoint used the last on-treatment visit with valid data, potentially including early termination. Differential discontinuation, especially for lack of efficacy in placebo recipients, complicates interpretation. Seven weeks also leaves uncertainty about sustained functional change.

What can reasonably be concluded?

This industry-sponsored trial provides randomized evidence for selected parent-rated benefits in a defined ADHD population. It does not validate a general claim that amphetamine improves every person’s functioning, establish driving safety or separate every expectation-related influence on parent ratings. This is a secondary analysis of the original trial, not an independent replication.

Scientific source

Banaschewski T, Soutullo C, Lecendreux M, et al. Health-Related Quality of Life and Functional Outcomes from a Randomized, Controlled Study of Lisdexamfetamine Dimesylate in Children and Adolescents with Attention Deficit Hyperactivity Disorder. CNS Drugs. 2013;27:829–840. doi:10.1007/s40263-013-0095-5. Original commentary on the supplied paper.