MinireviewAgreement between the results of meta-analyses from case reports and from clinical studies regarding the efficacy of laronidase therapy in patients with mucopolysaccharidosis type I who initiated enzyme replacement therapy in adult age: An example of case reports meta-analyses as an useful tool for evidence-based medicine in rare diseases
Introduction
Evidence-based medicine considers that randomized clinical trials (RCTs) provide the strongest evidence regarding the efficacy of new treatments in patients with a specific disease. On the other hand, case reports are considered as hypothesis generators with lower level grade of evidence [1].
However, RCTs can be more difficult to run for rare diseases due to lack of patients to be enrolled. In this case, the search for clinical knowledge regarding efficacy of pharmacological treatments and other kind of interventions may be based on observational studies and case reports.
In fact, there are situations in which non-controlled studies provide evidence of the same high quality as that provided by RCTs [2]. As an example, a study conducted with 189 phase 3 trials testing systemic cancer therapy, which cited phase 2 trials supporting the experimental arm, concluded that randomized controlled trials were not superior to single-arm trials predicting phase 3 study success [3].
Some publications consider case report research in rare diseases the lesser evil option, justified by the lack of patients and by case reports often being the first evidence of the effectiveness of a new therapy or new indication [4]. Due to their prominent role in rare diseases and their richness in details, there is an increasing interest in case reports analysis and in aggregating their results in systematic reviews [5], [6].
Although journals and publishers are beginning to develop case reports databases and there are recent initiatives to homogenize and upgrade quality of the information published in case reports (CARE guidelines) [7], questions related to how to aggregate them in ways that are meaningful remain unclear [6].
The efficacy of starting enzyme replacement therapy (ERT) in adults with Mucopolysaccharidosis type I (MPS-I) is controversial. A previous systematic review in MPS-I patients with ERT initiated in adult age (≥ 18 years) has been published [8]. The study combined results from 19 clinical studies selected to determine which endpoints improved after ERT was initiated in adult age. Twelve case reports were also described, but only the results of clinical studies were combined and graded in a meta-analysis. The aim of the present study is to assess the agreement between the results of the meta-analysis of those case reports and that of the clinical studies. As a secondary objective, we explored the role of meta-analyses of case reports as a tool for evidence-based medicine in rare diseases.
Section snippets
Data sources and study selection
A comprehensive search of journal articles and congress communications containing information on effectiveness of ERT for adult patients (≥ 18 years) with MPS-I (Hurler-Scheie syndrome and Scheie's syndrome) up to July 2016 was previously published [8], in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines [9]. The original papers were reviewed to select those meeting the following inclusion criteria: a) Studies conducted in patients with
Results
As previously mentioned there was a total of 11 case reports. Nine case reports described ERT administration at standard dose (100 UI/kg body weight administered once every week) and standard administration via (intravenous), one analyzed the effect of ERT on a pregnant woman [14], and the last one, the effects of treatment discontinuation (due to pregnancy) [14], [15]. The other two clinical reports analyzed the effect of ERT using different doses or administration via than the usual ones: One
Discussion
The diseases that meet the criterion of being rare are not limited to certain groups of genetic diseases traditionally known as such. The personalized medicine based on the developments of molecular diagnosis and genomic analysis has fragmented complex diseases into multiple molecular subtypes or strata [28]. In this regard, subtypes of different cancers would individually represent a rare disease [29]. Therefore, research methods derived from rare diseases, will become increasingly important
Conclusions
We found an agreement between the results from case reports- and clinical studies-meta-analyses in the efficacy of laronidase therapy in patients with MPS-I who initiated enzyme replacement therapy in adult age. We suggest that combining quantitatively results from case reports (confirmed with a strong confirmatory method), rather than analyzing them separately or qualitatively, can improve conclusions extracted regarding the effect of treatment. Therefore, case reports meta-analyses might help
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
References (37)
- et al.
Correlation of single arm versus randomised phase 2 oncology trial characteristics with phase 3 outcome
Eur. J. Cancer
(2015 Nov) - et al.
Efficacy of laronidase therapy in patients with mucopolysaccharidosis type I who initiated enzyme replacement therapy in adult age. A systematic review and meta-analysis
Mol. Genet. Metab.
(2017 Jun) - et al.
GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables
J. Clin. Epidemiol.
(2011 Apr) - et al.
GRADE guidelines: 9. Rating up the quality of evidence
J. Clin. Epidemiol.
(2011 Dec) - et al.
Laronidase for treating post-surgical respiratory failure in a patient with type I mucopolysaccharidosis
Farm. Hosp.
(2012 Jan-Feb) - et al.
Laronidase replacement therapy improves myocardial function in mucopolysaccharidosis I
Mol. Genet. Metab.
(2011 Jul) - et al.
Scheie syndrome diagnosed after cerebral infarction
J. Stroke Cerebrovasc. Dis.
(2012 May) - et al.
Mucopolysaccharidosis I (Scheie syndrome): a rare cause of severe aortic stenosis in a 31-year-old man
J. Formos. Med. Assoc.
(2015 Oct) - et al.
Immune tolerance induction for laronidase treatment in mucopolysaccharidosis I
Mol. Genet. Metab. Rep.
(2017 Mar) Medical case reports in the age of genomic medicine
Clin. Transl. Immunol.
(2015 Oct)