ObjectiveStuttering is a common childhood disorder. There is limited high quality evidence regarding options for best treatment. The aim of the study was to compare the effectiveness of direct treatment with indirect treatment in preschool children who stutter.MethodsIn this multicenter randomized controlled trial with an 18 month follow-up, preschool children who stutter who were referred for treatment were randomized to direct treatment (Lidcombe Program; n = 99) or indirect treatment (RESTART-DCM treatment; n = 100). Main inclusion criteria were age 3–6 years, ≥3% syllables stuttered (%SS), and time since onset ≥6 months. The primary outcome was the percentage of non-stuttering children at 18 months. Secondary outcomes included stuttering frequency (%SS), stuttering severity ratings by the parents and therapist, severity rating by the child, health-related quality of life, emotional and behavioral problems, and speech attitude.ResultsPercentage of non-stuttering children for direct treatment was 76.5% (65/85) versus 71.4% (65/91) for indirect treatment (Odds Ratio (OR), 0.6; 95% CI, 0.1–2.4, p = .42). At 3 months, children treated by direct treatment showed a greater decline in %SS (significant interaction time x therapy: β = -1.89; t(282.82) = -2.807, p = .005). At 18 months, stuttering frequency was 1.2% (SD 2.1) for direct treatment and 1.5% (SD 2.1) for indirect treatment. Direct treatment had slightly better scores on most other secondary outcome measures, but no differences between treatment approaches were significant.ConclusionsDirect treatment decreased stuttering more quickly during the first three months of treatment. At 18 months, however, clinical outcomes for direct and indirect treatment were comparable. These results imply that at 18 months post treatment onset, both treatments are roughly equal in treating developmental stuttering in ways that surpass expectations of natural recovery. Follow-up data are needed to confirm these findings in the longer term.Trial Registrationisrctn.org ISRCTN24362190

BackgroundAttention for Evidence Based Medicine (EBM) is growing, but evidence for orphan drugs is argued to be limited and inferior. This study systematically reviews the available evidence on clinical effectiveness, cost-effectiveness and budget impact for orphan drugs.MethodsA systematic review was performed in PubMed, Embase, NHS EED and HTA databases for 11 inpatient orphan drugs listed on the Dutch policy rule on orphan drugs. For included studies, we determined the type of study and various study characteristics.ResultsA total of 338 studies met all inclusion criteria. Almost all studies (96%) focused on clinical effectiveness of the drug. Of these studies, most studies were case studies (41%) or observational studies (39%). However, for all orphan diseases at least one experimental or quasi-experimental study was found, and a randomized clinical trial was available for 60% of the orphan drugs. Eight studies described the cost-effectiveness of an orphan drug; an equal number described an orphan drug’s budget impact.ConclusionsDespite the often heard claim that RCTs are not feasible for orphan drugs, we found that an RCT was available in 60% of orphan drugs investigated. Cost-effectiveness and budget impact analyses for orphan drugs are seldom published.

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