Sapropterin dihydrochloride for phenylketonuria
Appendices
Appendix 1. Glossary
| Technical term | Explanation |
| confidence interval | A measure of the uncertainty around the main finding of a statistical analysis. Estimates of unknown quantities, such as the odds ratio comparing an experimental intervention with a control, are usually presented as a point estimate and a 95% confidence interval. This means that if someone were to keep repeating a study in other samples from the same population, 95% of the confidence intervals from those studies would contain the true value of the unknown quantity. Alternatives to 95%, such as 90% and 99% confidence intervals, are sometimes used. Wider intervals indicate lower precision; narrow intervals, greater precision. |
| correlation coefficient | A correlation coefficient can range from ‐1 for perfect negative correlation, to +1 for perfect positive correlation (with perfect meaning that all the points lie on a straight line). A correlation coefficient of 0 means that there is no linear relationship between the variables. |
| cross‐over trial | A type of clinical trial comparing two or more interventions, in which the participants , upon completion of the course of one treatment, are switched to another. |
| encephalopathy | a disease of the brain; especially one involving alterations of brain structure |
| heterogeneity | used in a general sense to describe the variation in, or diversity of participants, interventions and measurement of outcomes across a set of studies, or the variation in internal validity of those studies. |
| intention‐to‐treat analysis | A strategy for analysing data from a randomised controlled trial. All participants are included in the arm to which they were allocated, whether or not they received (or completed) the intervention given to that arm. Intention‐to‐treat analysis prevents bias caused by the loss of participants, which may disrupt the baseline equivalence established by randomisation and which may reflect non‐adherence to the protocol. The term is often misused in trial publications when some participants were excluded. |
| meta‐analysis | The use of statistical techniques in a systematic review to integrate the results of included studies. Sometimes misused as a synonym for systematic reviews, where the review includes a meta‐analysis. |
| microcephaly | An abnormally small head of a newborn, a congenitally small brain. |
| neuropsychometric testing | Detailed testing of memory and other aspects of intellectual functioning such as planning, speed of thinking, abstract thinking, calculation, language (including speech and reading), visio‐spatial function and attention and concentration. It is often used to assess if there is evidence of intellectual or memory decline. When performed serially (eg at annual intervals) it can be used to detect evidence of change in intellectual functioning with time. |
| neurotoxicity | Toxicity to nervous tissue (both brain and peripheral nerves). |
| random‐effects model | A statistical model in which both within‐study sampling error (variance) and between‐studies variation are included in the assessment of the uncertainty (confidence interval) of the results of a meta‐analysis. When there is heterogeneity among the results of the included studies beyond chance, random‐effects models will give wider confidence intervals than fixed‐effect models. |
| standard deviation | A measure of the spread or dispersion of a set of observations, calculated as the average difference from the mean value in the sample. |
Appendix 2. Search strategy: ClinicalTrials.gov (all years)
| Search term |
| (kuvan OR phenoptin OR Sapropterin) AND (phenylketonuria OR PKU) |
Appendix 3. Search strategy: Current Controlled Trials (all years)
| Register | Search term |
| metaRegister (active register) | (kuvan OR phenoptin OR Sapropterin) AND (phenylketonuria OR PKU) |
