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Methodological issues in analyzing psychological test scores in pediatric clinical trials
J C Lindsey1, K O'Donnell, P Brouwers
1Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Insights
Pediatric clinical trials face unique data challenges. Ignoring issues like un-normable scores and instrument transitions can lead to incorrect conclusions about drug safety and efficacy in children.
Area of Science:
- Pediatric clinical pharmacology
- Biostatistics
- Neurodevelopmental assessment
Background:
- Clinical trials in children increasingly use cognitive tests to assess drug safety and efficacy.
- Analyzing repeated measures data in pediatric trials presents unique challenges beyond standard incomplete data issues.
- Common issues include un-normable raw scores due to severe illness and transitions between age-specific assessment tools.
Purpose of the Study:
- To highlight the unique data analysis challenges in pediatric clinical trials involving cognitive assessments.
- To discuss the potential consequences of ignoring these challenges on treatment efficacy and safety conclusions.
- To propose a simple approach for evaluating the impact of these issues on statistical analyses.
Main Methods:
- Review of common data complexities in pediatric drug trials, such as un-normable scores and instrument changes.
- Description of the potential impact of these complexities on statistical inference.
- Illustration of a proposed impact assessment method using data from a Phase III HIV-infected children trial.
Main Results:
- Cognitive assessment data in pediatric trials can be compromised by severe illness affecting raw scores.
- Children transitioning between age-appropriate cognitive instruments create analytical complexities.
- These issues, if unaddressed, can lead to erroneous conclusions about drug efficacy and safety.
Conclusions:
- Standard statistical methods may be inadequate for pediatric clinical trial data with unique complexities.
- Careful consideration and appropriate methods are crucial to avoid biased results in pediatric drug development.
- A proposed simple approach can help assess the impact of these data issues on trial outcomes.
Abstract:
Clinical trials to address drug dosing, safety, and efficacy issues in the pediatric population are becoming more common. In some studies, tests of mental ability are administered at regular intervals in drug trials for treatment of children with HIV, certain types of cancer, sickle cell anemia, and diabetes. The test scores are used to examine differences between treatments in efficacy and safety over time. In addition to the well-known problems of analyzing repeated measures with incomplete data profiles, the analyses of these data are complicated by a number of unique features, including that children can be so ill that their raw scores cannot be mapped to a normed scaled score, and that children may be in the studies long enough that they transition between the age-appropriate instruments. These issues are often ignored in data analyses and can potentially cause incorrect conclusions regarding treatment efficacy and safety. This article describes these issues and their possible consequences. A simple approach to determine their impact on the statistical analysis of a particular clinical trial is suggested. The approach is illustrated with data from a Phase III trial in HIV-infected children.