Outcomes in pediatric studies of medium-chain acyl-coA dehydrogenase (MCAD) deficiency and phenylketonuria (PKU): a review

被引：17

作者：

Pugliese, Michael ^{[1
]}

Tingley, Kylie ^{[1
]}

Chow, Andrea ^{[1
]}

Pallone, Nicole ^{[2
]}

Smith, Maureen ^{[3
]}

Rahman, Alvi ^{[1
]}

Chakraborty, Pranesh ^{[4
]}

Geraghty, Michael T. ^{[5
,6
]}

Irwin, Julie ^{[7
]}

Tessier, Laure ^{[4
]}

Nicholls, Stuart G. ^{[8
]}

Offringa, Martin ^{[9
,10
]}

Butcher, Nancy J. ^{[10
]}

Iverson, Ryan ^{[1
]}

Clifford, Tammy J. ^{[1
]}

Stockler, Sylvia ^{[11
]}

Hutton, Brian ^{[1
]}

Paik, Karen ^{[1
]}

Tao, Jessica ^{[12
]}

Skidmore, Becky ^{[8
]}

Coyle, Doug ^{[1
]}

Duddy, Kathleen ^{[11
]}

Dyack, Sarah ^{[13
]}

Greenberg, Cheryl R. ^{[14
]}

Ghai, Shailly Jain ^{[15
]}

Karp, Natalya ^{[16
]}

Korngut, Lawrence ^{[17
]}

Kronick, Jonathan ^{[9
,18
]}

MacKenzie, Alex ^{[19
]}

MacKenzie, Jennifer ^{[20
]}

Maranda, Bruno ^{[21
]}

Mitchell, John J. ^{[22
]}

Potter, Murray ^{[23
]}

Prasad, Chitra ^{[16
]}

Schulze, Andreas ^{[9
]}

Sparkes, Rebecca ^{[24
]}

Taljaard, Monica ^{[1
,8
]}

Trakadis, Yannis ^{[25
]}

Walia, Jagdeep ^{[26
]}

Potter, Beth K. ^{[1
]}

机构：

[1] Univ Ottawa, Sch Epidemiol & Publ Hlth, Ottawa, ON, Canada

[2] Canadian PKU & Allied Disorders Inc, Sparwood, BC, Canada

[3] Canadian Org Rare Disorders, Ottawa, ON, Canada

[4] Childrens Hosp Eastern Ontario, Newborn Screening Ontario, Ottawa, ON, Canada

[5] Childrens Hosp Eastern Ontario, Div Metab & Newborn Screening, Ottawa, ON, Canada

[6] Univ Ottawa, Ottawa, ON, Canada

[7] Childrens Hosp Eastern Ontario, Ambulatory Care, Ottawa, ON, Canada

[8] Ottawa Hosp Res Inst, Clin Epidmiol Program, Ottawa, ON, Canada

[9] Univ Toronto, Dept Pediat, Toronto, ON, Canada

[10] Hosp Sick Children, Child Hlth Evaluat Sci, Res Inst, Toronto, ON, Canada

[11] BC Childrens Hosp, Biochem Dis, Vancouver, BC, Canada

[12] Univ Ottawa, Fac Med, Ottawa, ON, Canada

[13] IWK Hlth Ctr, Div Med Genet, Halifax, NS, Canada

[14] Univ Manitoba, Dept Pediat & Child Hlth, Winnipeg, MB, Canada

[15] Univ Alberta, Dept Med Genet, Edmonton, AB, Canada

[16] Western Univ, Dept Pediat, London, ON, Canada

[17] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada

[18] Hosp Sick Children, Clin & Metab Genet, Toronto, ON, Canada

[19] Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada

[20] McMaster Univ, Dept Pediat, Hamilton, ON, Canada

[21] Univ Sherbrooke, Dept Pediat, Sherbrooke, PQ, Canada

[22] McGill Univ, Human Genet & Pediat, Montreal, PQ, Canada

[23] McMaster Univ, Pathol & Mol Med, Hamilton, ON, Canada

[24] Univ Calgary, Med Genet & Pediat, Calgary, AB, Canada

[25] McGill Univ, Ctr Hlth, Human Genet & Med Genet, Montreal, PQ, Canada

[26] Queens Univ, Dept Pediat, Kingston, ON, Canada

来源：

ORPHANET JOURNAL OF RARE DISEASES | 2020年 / 15卷 / 01期

基金：

加拿大健康研究院;

关键词：

PKU; MCAD deficiency; Core outcome sets; Rare diseases; Patient-oriented outcomes; CLINICAL-TRIALS; DOUBLE-BLIND; MANAGEMENT; DIAGNOSIS;

D O I：

10.1186/s13023-019-1276-1

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background Inherited metabolic diseases (IMDs) are a group of individually rare single-gene diseases. For many IMDs, there is a paucity of high-quality evidence that evaluates the effectiveness of clinical interventions. Clinical effectiveness trials of IMD interventions could be supported through the development of core outcome sets (COSs), a recommended minimum set of standardized, high-quality outcomes and associated outcome measurement instruments to be incorporated by all trials in an area of study. We began the process of establishing pediatric COSs for two IMDs, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and phenylketonuria (PKU), by reviewing published literature to describe outcomes reported by authors, identify heterogeneity in outcomes across studies, and assemble a candidate list of outcomes. Methods We used a comprehensive search strategy to identify primary studies and guidelines relevant to children with MCAD deficiency and PKU, extracting study characteristics and outcome information from eligible studies including outcome measurement instruments for select outcomes. Informed by an established framework and a previously published pediatric COS, outcomes were grouped into five, mutually-exclusive, a priori core areas: growth and development, life impact, pathophysiological manifestations, resource use, and death. Results For MCAD deficiency, we identified 83 outcomes from 52 articles. The most frequently represented core area was pathophysiological manifestations, with 33 outcomes reported in 29/52 articles (56%). Death was the most frequently reported outcome. One-third of outcomes were reported by a single study. The most diversely measured outcome was cognition and intelligence/IQ for which eight unique measurement instruments were reported among 14 articles. For PKU, we identified 97 outcomes from 343 articles. The most frequently represented core area was pathophysiological manifestations with 31 outcomes reported in 281/343 articles (82%). Phenylalanine concentration was the most frequently reported outcome. Sixteen percent of outcomes were reported by a single study. Similar to MCAD deficiency, the most diversely measured PKU outcome was cognition and intelligence/IQ with 39 different instruments reported among 82 articles. Conclusions Heterogeneity of reported outcomes and outcome measurement instruments across published studies for both MCAD deficiency and PKU highlights the need for COSs for these diseases, to promote the use of meaningful outcomes and facilitate comparisons across studies.

引用

页数：15

共 29 条

[1]

[Anonymous], 2018, Cadth

[2]

[Anonymous], J GLOB HLTH

[3]

[Anonymous], 2017, TRIALS S3, DOI DOI 10.1186/S12891-017-1660-8

[4] Clinical Trials in Rare Disease: Challenges and Opportunities [J].