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Editors' Note: Commenting on “Behavioral and cognitive outcomes for clinical trials in children with neurofibromatosis type 1,” Walsh et al. disagree with the authors' suggestion to utilize a broad-based battery in clinical trials. Instead, they suggest researchers should select hypothesis-driven domains for a trial. They also encourage neurofibromatosis researchers to participate in the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration. Moll et al., authors of the study, defend their methods and suggest that the pragmatic approach and the explanatory approach can be used in parallel. To Dr. Kang, the “Moderate alcohol intake reduces risk of ischemic stroke in Korea” study may have overestimated the beneficial effect of alcohol because many of the nondrinkers may be ALDH2 deficient, putting them at a higher risk for vascular disease. Bae et al., authors of the study, agree in part with Dr. Kang but caution that there is not enough evidence for ALDH gene polymorphism as an independent risk factor for stroke and that further research is warranted.—Chafic Karam, MD, and Robert C. Griggs, MD
We commend van der Vaart et al. for addressing the important topic of outcomes in neurofibromatosis type 1 (NF1) clinical trials and their use of quantitative data to document areas of impairment and examine the psychometric properties of potential measures.1 However, the authors' suggestion to utilize a broad-based battery in clinical trials does not align with scientific methodology.
Researchers should select hypothesis-driven domains for a trial. Numerous measures are available to assess each domain, and careful selection of outcome tools is vital. Appropriate outcome measures must have adequate psychometric properties to detect change and demonstrate reliability and validity in evaluating targeted domains. As noted by the authors, there is a lack of consensus regarding which measures meet these criteria.
As research moves forward, it is crucial that the field identifies appropriate tools for consistent use in the NF1 population across trials. To this end, the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration has been working to reach consensus on clinical trials endpoints since 2011.2,3 Initial recommendations regarding cognitive and patient-reported outcome measures are forthcoming. We encourage neurofibromatosis researchers conducting clinical trials to participate in REiNS and consult the published guidelines when considering trial endpoints.
We thank Walsh et al. for the interest in our article.1 We also applaud the REiNS initiative for their efforts in finding consensus on outcome measures for neurofibromatosis.
Our article provided detailed information on the appropriateness of the outcome measures that were used in the NF1-SIMCODA trial, including psychometric properties and cross-correlations.1 This trial was a predominantly pragmatic trial seeking clinical improvement in measures relevant for patients, considering the notion that changes on intermediate or explanatory outcome measures are not final proof of clinically relevant effects. Nonetheless, some more explanatory outcome measures were selected based on hypotheses and included in the secondary outcomes.4
The choice for pragmatic outcome measures or for explanatory outcome measures depends on the goal of the clinical trial.5 If the goal is to provide a biological proof of principle, explanatory outcome measures may be used as we have done previously in NF1.6 If the goal is to decide whether a certain treatment should be given to children with learning disabilities, a clinically relevant pragmatic outcome measure is needed. In our experience, the pragmatic approach and the explanatory approach can be used in parallel. We anticipate that detailed analysis of existing data resources will help to improve future recommendations.
Footnotes
Author disclosures are available upon request (journal@neurology.org).
References
1.van der Vaart T, Rietman AB, Plasschaert E, et al. Behavioral and cognitive outcomes for clinical trials in children with neurofibromatosis type 1. Neurology
2016;86:154–160. [DOI] [PMC free article] [PubMed] [Google Scholar]
2.Plotkin SR, Blakeley JO, Dombi E, et al. Achieving consensus for clinical trials: the REiNS International Collaboration. Neurology
2013;81:S1–S5. [DOI] [PMC free article] [PubMed] [Google Scholar]
3.Widemann BC, Blakeley JO, Dombi E, et al. Conclusions and future directions for the REiNS International Collaboration. Neurology
2013;81:S41–S44. [DOI] [PMC free article] [PubMed] [Google Scholar]
4.van der Vaart T, Plasschaert E, Rietman AB, et al. Simvastatin for cognitive deficits and behavioural problems in patients with neurofibromatosis type 1 (NF1-SIMCODA): a randomised, placebo-controlled trial. Lancet Neurol
2013;12:1076–1083. [DOI] [PubMed] [Google Scholar]
5.Thorpe KE, Zwarenstein M, Oxman AD, et al. A pragmatic-explanatory continuum indicator summary (PRECIS): a tool to help trial designers. J Clin Epidemiol
2009;62:464–475. [DOI] [PubMed] [Google Scholar]
6.Krab LC, de Goede-Bolder A, Aarsen FK, et al. Effect of simvastatin on cognitive functioning in children with neurofibromatosis type 1: a randomized controlled trial. JAMA
2008;300:287–294. [DOI] [PMC free article] [PubMed] [Google Scholar]
