Systematic reviews of rare diseases can be challenging to conduct, partly due to limited published data. Novel methods of data acquisition may be helpful in addition to conventional search methods to obtain further data. Clinical experts and patient organisation representatives (PORs) have a direct link to patients and are likely to have up to date information and unpublished data on patient numbers, patient characteristics, treatment patterns and resource use. In some instances, a single centre can be responsible for treating all identified rare disease patients in a single country. Involvement of clinical experts and POR is recommended in both the guidance issued by the Centre for Reviews and Dissemination (CRD) and Risk of Bias in Systematic Reviews (ROBIS) assessment.
To compare data contributed by clinical experts and POR to data provided by publications obtained through traditional searching methods in two systematic reviews of rare diseases.
We conducted systematic reviews of Morquio A syndrome and neuronal ceroid lipofuscinosis type 2 (CLN2 disease). Both contained traditional search methods (database searching, reference checking) and an additional survey of clinical experts and POR. We analysed the results to determine what proportion from each source contributed to answering individual research questions.
In the systematic review of Morquio A, clinical experts and POR contributed 75% of point prevalence data and 19% of birth prevalence data. In the systematic review of CLN2 disease, clinical experts and POR contributed 50% of point prevalence data; 42.9% of birth prevalence data; 52.6% of patient demographic data; 52.6% of diagnostic data; 62.5% of severity of disease data and 100% of resource use data.
Clinical experts and POR are an invaluable source of information in rare diseases, especially where evidence gaps exist in the published literature. The methodology of systematic reviews of rare diseases is an emerging field, where published data has historically been limited. Novel supplementary searching methods can easily be combined with traditional methods to create a more comprehensive systematic review.
Patient or healthcare consumer involvement:
The clinical experts and POR contacted during the systematic reviews of Morquio A syndrome and CLN2 disease provide a direct link to patients and healthcare consumers.