Design and analysis features used in small population and rare disease trials: A targeted review

Partington, Giles; Cro, Suzie; Mason, Alexina J.; Cornelius, Victoria

doi:10.1016/j.jclinepi.2021.12.009

Cited by 7 publications

(5 citation statements)

References 11 publications

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“…The key question now is how the evidence base for managing monogenic severe IR can be improved in the face of constraints in studying rare, clinically heterogeneous, and geographically dispersed patients who are often diagnosed late with a condition that is exquisitely environmentally sensitive. Growing interest in and development of methodologies for clinical trials in rare disease 62 , including Bayesian methodologies 63 , 64 , and hybrid single- and multi-site designs 65 offer hope for future filling of evidence gaps. One important and pragmatic opportunity arises from the development of large regional, national and international networks and registries for lipodystrophy (e.g.…”

Section: Discussionmentioning

confidence: 99%

Genotype-stratified treatment for monogenic insulin resistance: a systematic review

Semple,

Patel,

Auh

et al. 2023

Commun Med

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Background Monogenic insulin resistance (IR) includes lipodystrophy and disorders of insulin signalling. We sought to assess the effects of interventions in monogenic IR, stratified by genetic aetiology. Methods Systematic review using PubMed, MEDLINE and Embase (1 January 1987 to 23 June 2021). Studies reporting individual-level effects of pharmacologic and/or surgical interventions in monogenic IR were eligible. Individual data were extracted and duplicates were removed. Outcomes were analysed for each gene and intervention, and in aggregate for partial, generalised and all lipodystrophy. Results 10 non-randomised experimental studies, 8 case series, and 23 case reports meet inclusion criteria, all rated as having moderate or serious risk of bias. Metreleptin use is associated with the lowering of triglycerides and haemoglobin A1c (HbA1c) in all lipodystrophy (n = 111), partial (n = 71) and generalised lipodystrophy (n = 41), and in LMNA, PPARG, AGPAT2 or BSCL2 subgroups (n = 72,13,21 and 21 respectively). Body Mass Index (BMI) is lowered in partial and generalised lipodystrophy, and in LMNA or BSCL2, but not PPARG or AGPAT2 subgroups. Thiazolidinediones are associated with improved HbA1c and triglycerides in all lipodystrophy (n = 13), improved HbA1c in PPARG (n = 5), and improved triglycerides in LMNA (n = 7). In INSR-related IR, rhIGF-1, alone or with IGFBP3, is associated with improved HbA1c (n = 17). The small size or absence of other genotype-treatment combinations preclude firm conclusions. Conclusions The evidence guiding genotype-specific treatment of monogenic IR is of low to very low quality. Metreleptin and Thiazolidinediones appear to improve metabolic markers in lipodystrophy, and rhIGF-1 appears to lower HbA1c in INSR-related IR. For other interventions, there is insufficient evidence to assess efficacy and risks in aggregated lipodystrophy or genetic subgroups.

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Section: Discussionmentioning

confidence: 99%

Genotype-stratified treatment for monogenic insulin resistance: a systematic review

Semple,

Patel,

Auh

et al. 2023

Commun Med

View full text Add to dashboard Cite

show abstract

“…The key question now is how the evidence base for managing monogenic severe IR can be improved in the face of constraints in studying rare, clinically heterogeneous, and geographically dispersed patients who are often diagnosed late with a condition that is exquisitely environmentally sensitive. Growing interest in and development of methodologies for clinical trials in rare disease 58 , including Bayesian methodologies 59,60 , for use under a CC0 license. and hybrid single-and multi-site designs 61 offer hope for future filling of evidence gaps.…”

Section: Discussionmentioning

confidence: 99%

Systematic review of genotype-stratified treatment for monogenic insulin resistance

Semple

Patel

Auh

et al. 2023

Preprint

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ObjectiveTo assess the effects of pharmacologic and/or surgical interventions in monogenic insulin resistance (IR), stratified by genetic aetiology.DesignSystematic review.Data sourcesPubMed, MEDLINE and Embase, from 1 January 1987 to 23 June 2021.Review methodsStudies reporting individual-level effects of pharmacologic and/or surgical interventions in monogenic IR were eligible. Individual subject data were extracted and duplicate data removed. Outcomes were analyzed for each affected gene and intervention, and in aggregate for partial, generalised and all lipodystrophy.Results10 non-randomised experimental studies, 8 case series, and 21 single case reports met inclusion criteria, all rated as having moderate or serious risk of bias. Metreleptin was associated with lower triglycerides and hemoglobin A1c in aggregated lipodystrophy (n=111), in partial lipodystrophy (n=71) and generalised lipodystrophy (n=41)), and inLMNA,PPARG,AGPAT2orBSCL2subgroups (n=72,13,21 and 21 respectively). Body Mass Index (BMI) was lower after treatment in partial and generalised lipodystrophy overall, and inLMNA or BSCL2, but notPPARGorAGPAT2subgroups. Thiazolidinedione use was associated with improved hemoglobin A1c and triglycerides in aggregated lipodystrophy (n=13), improved hemoglobin A1c only in thePPARGsubgroup (n=5), and improved triglycerides only in theLMNAsubgroup (n=7). InINSR-related IR, use of rhIGF-1, alone or with IGFBP3, was associated with improved hemoglobin A1c (n=15). The small size or absence of all other genotype-treatment combinations precluded firm conclusions.ConclusionsThe evidence guiding genotype-specific treatment of monogenic IR is of low to very low quality. Metreleptin and Thiazolidinediones appear to have beneficial metabolic effects in lipodystrophy, and rhIGF-1 appears to lower hemoglobin A1c in INSR-related IR. For other interventions there is insufficient evidence to assess efficacy and risks either in aggregated lipodystrophy or in genetic subgroups. There is a pressing need to improve the evidence base for management of monogenic IR.

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“…Stage 2: SCOPUS toggle switches were used to (2) screen and filter "articles" that were "peer-reviewed" in "English" which reduced the papers to 144. Stage 3: The papers were assessed for (3) eligibility by the reviewers with the aid of Rayyan AI, an AI tool deemed helpful by multiple researchers [44,45]. Exclusion criteria were developed through studying multiple PPP reviews and are as follows:…”

Section: Paper Filtering Stagesmentioning

confidence: 99%

Critical Success Factors of Water and Power Public–Private Partnerships in Developing Countries: A Systematic Review

Aljaber,

Sohail,

Ruikar

2024

Buildings

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Public–private partnerships (PPP) have evolved as a choice of infrastructure procurement for numerous developing countries, particularly in the water and power sectors, thereby capturing the interest of researchers. A rich body of literature exists in the field of PPPs, as well as their critical success factors (CSF). Despite the valuable insights garnered from individual studies, a research gap exists in conducting a meta-synthesis of the findings from multiple developing countries and investigating the broader elements and themes of power and water PPP CSF research. This systematic review employed the PRISMA protocol and identified 30 records. We explored the regions, sectors, yearly output, adopted research methods, key authors, and themes of the corpus reviewed. The review recognised four emerging trends in the records, which are identifying, ranking, exploring the interrelationship, or utilising CSFs. The review identified the top 30 frequent CSFs in the corpus, as well as their ranking by importance across multiple settings. The review concludes by addressing geographic and methodological limitations and proposing directions for future research.

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Design and analysis features used in small population and rare disease trials: A targeted review

Cited by 7 publications

References 11 publications

Genotype-stratified treatment for monogenic insulin resistance: a systematic review

Genotype-stratified treatment for monogenic insulin resistance: a systematic review

Systematic review of genotype-stratified treatment for monogenic insulin resistance

Critical Success Factors of Water and Power Public–Private Partnerships in Developing Countries: A Systematic Review

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