Clinical trial NCT01603407: Finding the Optimum Regimen for Duchenne Muscular Dystrophy
Official title: Duchenne Muscular Dystrophy: Double-blind Randomized Trial to Find Optimum Steroid Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Duchenne Muscular Dystrophy
Keywords: prednisone
deflazacort
muscular dystrophy
neuromuscular disease
multi-center
Lead sponsor: University of Rochester
Sponsor class: OTHER
Collaborators: name: Newcastle University
name: University Medical Center Freiburg
name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2012-05-23
Enrollment: 196
Sex: MALE
Minimum age (years): 4
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The Finding the Optimum Regimen for Duchenne Muscular Dystrophy (FOR DMD) study will compare three ways of giving corticosteroids to boys with Duchenne muscular dystrophy (DMD) to determine which of the three ways increases muscle strength the most, and which causes the fewest side effects. Using the results of this study, the investigators aim to provide patients and families with clearer information about the best way to take these drugs.

Detailed description: Boys with Duchenne muscular dystrophy experience progressive muscle weakness as they grow up. Corticosteroids are currently the only medicine that has been shown to increase muscle strength in boys with DMD. Benefits include an increase in the length of time that boys could continue to walk, reduction in the development of curvature of the spine, a longer time of adequate breathing, and possible protection against the development of heart problems.

Doctors have tried different ways of prescribing corticosteroids in order to decrease undesirable side effects of the drug. No controlled, long-term study has ever looked at the effects of different corticosteroids to see which one improves strength the most and which one causes the fewest side effects, over a period of time. Different doctors in different countries prescribe the drugs in different ways, and some do not prescribe corticosteroids at all.

The FOR DMD study will enroll boys with DMD ages 4-7. The study will look at three ways of taking the following corticosteroids by the mouth to determine which increases muscle strength the most, and which causes the fewest side effects:

1. Prednisone 0.75mg/kg/day
2. Prednisone 0.75mg/kg/day switching between 10 days on and 10 days off treatment
3. Deflazacort 0.9mg/kg/day.

The study will take place at 40 academic medical centers in the United States, Canada, United Kingdom, Germany and Italy.

Eligibility criteria: Inclusion Criteria:

* Evidence of signed and dated informed consent form.
* Confirmed diagnosis of Duchenne muscular dystrophy
* Age greater than or equal to 4 years and less than 8 years old
* Ability to rise independently from floor, from supine to standing
* Willingness and ability to comply with scheduled visits, drug administration plan and study procedures
* Ability to maintain reproducible FVC measurements.

Exclusion Criteria:

* History of major renal or hepatic impairment, immunosuppression or other contraindications to corticosteroid therapy.
* History of chronic systemic fungal or viral infections. Acute bacterial infection(including TB) would exclude from enrolment until the infection had been appropriately treated and resolved.
* Diabetes mellitus.
* Idiopathic hypercalcuria.
* Lack of chicken pox immunity and refusal to undergo immunization.
* Evidence of symptomatic cardiomyopathy at screening assessment (one to three months prior to the baseline visit). Asymptomatic cardiac abnormality on investigation would not be an exclusion.
* Current or previous treatment (greater than four consecutive weeks of oral therapy) with corticosteroids or other immunosuppressive treatments for DMD or other recurrent indications (e.g., asthma), unless approved by FOR-DMD Team (i.e., concurrent participation in another allowed DMD trial).
* Inability to take tablets, as assessed by the site investigator by the end of the screening period (the screening period ranges from one to three months prior to the baseline visit).
* Allergy/sensitivity to study drugs or their formulations including lactose and/or sucrose intolerance.
* Severe behavioral problems, including severe autism.
* Previous or ongoing medical condition, medical history, physical findings or laboratory abnormalities that could affect safety, make it unlikely that treatment and follow up will be correctly completed or impair the assessment of study results, in the judgment of the site investigator.
* Weight of less than 13 kilograms.
* Exposure to any investigational drug currently or within 3 months prior to start of study treatment.

Primary outcomes:
measure: Forced Vital Capacity
timeFrame: Average of Months 3, 6, 12, 18, 24, 30 and 36 visits
measure: Rise From the Floor Velocity
timeFrame: Average of Months 3, 6, 12, 18, 24, 30 and 36 visits
measure: Treatment Satisfaction Questionnaire for Medication (TSQM) Global Satisfaction With Treatment Score
timeFrame: Average of Months 3, 6, 12, 18, 24, 30 and 36 visits
Secondary outcomes:
measure: North Star Ambulatory Assessment (NSAA) Score
timeFrame: Average of Months 3, 6, 12, 18, 24, 30 and 36 visits
measure: 6 Minute Walk Test
timeFrame: Average of Months 3, 6, 12, 18, 24, 30 and 36 visits
measure: Range of Motion (Goniometry) of Left Ankle
timeFrame: Average of Months 3, 6, 12, 18, 24, 30 and 36 visits
measure: Range of Motion (Goniometry) of Right Ankle
timeFrame: Average of Months 3, 6, 12, 18, 24, 30 and 36 visits
measure: Number of Participants Who Tolerated the Regimen
timeFrame: 3 years
measure: Heart Rate
timeFrame: 36 months
measure: Quality of Life - Parent
timeFrame: Average of Months 12, 24, and 36 visits
measure: Quality of Life- Child
timeFrame: Average of Months 12, 24, and 36 visits
measure: Left Ventricular Ejection Fraction Percent
timeFrame: 36 months
measure: Fractional Shortening Percent
timeFrame: 36 months
measure: PR Interval
timeFrame: 36 months
measure: Participant Weight
timeFrame: 36 months
measure: Participant Height
timeFrame: 36 months
measure: Participant Body Mass Index
timeFrame: 36 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles (UCLA) Medical Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Albuquerque
country: United States
facility: University of New Mexico Health Science Center
state: New Mexico
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Children's Hospital
state: Tennessee
city: Salt Lake City
country: United States
facility: University of Utah Medical Center
state: Utah
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: London
country: Canada
facility: Children's Hospital London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario (CHEO)
state: Ontario
city: Dresden
country: Germany
facility: Children's Hospital, Technical University Dresden
city: Essen
country: Germany
facility: University Hospital of Essen
city: Freiburg
country: Germany
facility: University Medical Center Freiburg
city: Göttingen
country: Germany
facility: Children's University Hospital, Göttingen
city: Messina
country: Italy
facility: University of Messina AOU Policlinico Gaetano Martino
city: Milan
country: Italy
facility: C. Besta Neurological Institute Foundation
city: Padova
country: Italy
facility: University of Padova School of Medicine
city: Torino
country: Italy
facility: Neuromuscular Center University of Turin
city: Leeds
country: United Kingdom
facility: The General Infirmary at Leeds
state: England
city: Glasgow
country: United Kingdom
facility: Greater Glasgow and Clyde NHS Yorkhill Hospital
state: Scotland
city: Birmingham
country: United Kingdom
facility: Heart of England NHS Foundation Trust Birmingham Heartland's Hospital
city: Liverpool
country: United Kingdom
facility: Alder Hey Children's Hospital NHS Trust
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children NHS Trust
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: Institute of Human Genetics, International Centre for Life
Study officials:
affiliation: University of Rochester
name: Robert C. Griggs, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Newcastle University
name: Kate Bushby, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Angelini C, Pegoraro E, Turella E, Intino MT, Pini A, Costa C. Deflazacort in Duchenne dystrophy: study of long-term effect. Muscle Nerve. 1994 Apr;17(4):386-91. doi: 10.1002/mus.880170405.
citation: Atkinson MJ, Sinha A, Hass SL, Colman SS, Kumar RN, Brod M, Rowland CR. Validation of a general measure of treatment satisfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM), using a national panel study of chronic disease. Health Qual Life Outcomes. 2004 Feb 26;2:12. doi: 10.1186/1477-7525-2-12.
citation: Backman E, Henriksson KG. Low-dose prednisolone treatment in Duchenne and Becker muscular dystrophy. Neuromuscul Disord. 1995 May;5(3):233-41. doi: 10.1016/0960-8966(94)00048-e.
citation: Bianchi ML. How to manage osteoporosis in children. Best Pract Res Clin Rheumatol. 2005 Dec;19(6):991-1005. doi: 10.1016/j.berh.2005.06.006.
citation: Biggar WD, Bachrach LK, Henderson RC, Kalkwarf H, Plotkin H, Wong BL. Bone health in Duchenne muscular dystrophy: a workshop report from the meeting in Cincinnati, Ohio, July 8, 2004. Neuromuscul Disord. 2005 Jan;15(1):80-5. doi: 10.1016/j.nmd.2004.09.010. No abstract available.
citation: Biggar WD, Gingras M, Fehlings DL, Harris VA, Steele CA. Deflazacort treatment of Duchenne muscular dystrophy. J Pediatr. 2001 Jan;138(1):45-50. doi: 10.1067/mpd.2001.109601.
citation: Biggar WD, Harris VA, Eliasoph L, Alman B. Long-term benefits of deflazacort treatment for boys with Duchenne muscular dystrophy in their second decade. Neuromuscul Disord. 2006 Apr;16(4):249-55. doi: 10.1016/j.nmd.2006.01.010. Epub 2006 Mar 20.
citation: Biggar WD, Politano L, Harris VA, Passamano L, Vajsar J, Alman B, Palladino A, Comi LI, Nigro G. Deflazacort in Duchenne muscular dystrophy: a comparison of two different protocols. Neuromuscul Disord. 2004 Sep;14(8-9):476-82. doi: 10.1016/j.nmd.2004.05.001.
citation: Brooke MH, Fenichel GM, Griggs RC, Mendell JR, Moxley R, Miller JP, Province MA. Clinical investigation in Duchenne dystrophy: 2. Determination of the "power" of therapeutic trials based on the natural history. Muscle Nerve. 1983 Feb;6(2):91-103. doi: 10.1002/mus.880060204.
citation: Brooke MH, Fenichel GM, Griggs RC, Mendell JR, Moxley RT 3rd, Miller JP, Kaiser KK, Florence JM, Pandya S, Signore L, et al. Clinical investigation of Duchenne muscular dystrophy. Interesting results in a trial of prednisone. Arch Neurol. 1987 Aug;44(8):812-7. doi: 10.1001/archneur.1987.00520200016010.
citation: Brooke MH, Fenichel GM, Griggs RC, Mendell JR, Moxley R, Florence J, King WM, Pandya S, Robison J, Schierbecker J, et al. Duchenne muscular dystrophy: patterns of clinical progression and effects of supportive therapy. Neurology. 1989 Apr;39(4):475-81. doi: 10.1212/wnl.39.4.475.
citation: Bushby K, Muntoni F, Urtizberea A, Hughes R, Griggs R. Report on the 124th ENMC International Workshop. Treatment of Duchenne muscular dystrophy; defining the gold standards of management in the use of corticosteroids. 2-4 April 2004, Naarden, The Netherlands. Neuromuscul Disord. 2004 Sep;14(8-9):526-34. doi: 10.1016/j.nmd.2004.05.006. No abstract available.
citation: Bushby K, Muntoni F, Bourke JP. 107th ENMC international workshop: the management of cardiac involvement in muscular dystrophy and myotonic dystrophy. 7th-9th June 2002, Naarden, the Netherlands. Neuromuscul Disord. 2003 Feb;13(2):166-72. doi: 10.1016/s0960-8966(02)00213-4. No abstract available.
citation: Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, Shapiro F, Tomezsko J, Constantin C; DMD Care Considerations Working Group. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 2010 Jan;9(1):77-93. doi: 10.1016/S1474-4422(09)70271-6. Epub 2009 Nov 27.
citation: Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, Shapiro F, Tomezsko J, Constantin C; DMD Care Considerations Working Group. Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care. Lancet Neurol. 2010 Feb;9(2):177-89. doi: 10.1016/S1474-4422(09)70272-8. Epub 2009 Nov 27.
citation: Carter GT, McDonald CM. Preserving function in Duchenne dystrophy with long-term pulse prednisone therapy. Am J Phys Med Rehabil. 2000 Sep-Oct;79(5):455-8. doi: 10.1097/00002060-200009000-00009.
citation: Collett BR, Ohan JL, Myers KM. Ten-year review of rating scales. V: scales assessing attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2003 Sep;42(9):1015-37. doi: 10.1097/01.CHI.0000070245.24125.B6.
citation: Collett BR, Ohan JL, Myers KM. Ten-year review of rating scales. VI: scales assessing externalizing behaviors. J Am Acad Child Adolesc Psychiatry. 2003 Oct;42(10):1143-70. doi: 10.1097/00004583-200310000-00006.
citation: Connolly AM, Schierbecker J, Renna R, Florence J. High dose weekly oral prednisone improves strength in boys with Duchenne muscular dystrophy. Neuromuscul Disord. 2002 Dec;12(10):917-25. doi: 10.1016/s0960-8966(02)00180-3.
citation: Duboc D, Meune C, Lerebours G, Devaux JY, Vaksmann G, Becane HM. Effect of perindopril on the onset and progression of left ventricular dysfunction in Duchenne muscular dystrophy. J Am Coll Cardiol. 2005 Mar 15;45(6):855-7. doi: 10.1016/j.jacc.2004.09.078.
citation: Dubowitz V, Kinali M, Main M, Mercuri E, Muntoni F. Remission of clinical signs in early duchenne muscular dystrophy on intermittent low-dosage prednisolone therapy. Eur J Paediatr Neurol. 2002;6(3):153-9. doi: 10.1053/ejpn.2002.0583.
citation: Eagle M, Baudouin SV, Chandler C, Giddings DR, Bullock R, Bushby K. Survival in Duchenne muscular dystrophy: improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Neuromuscul Disord. 2002 Dec;12(10):926-9. doi: 10.1016/s0960-8966(02)00140-2.
citation: Fenichel GM, Florence JM, Pestronk A, Mendell JR, Moxley RT 3rd, Griggs RC, Brooke MH, Miller JP, Robison J, King W, et al. Long-term benefit from prednisone therapy in Duchenne muscular dystrophy. Neurology. 1991 Dec;41(12):1874-7. doi: 10.1212/wnl.41.12.1874.
citation: Fenichel GM, Mendell JR, Moxley RT 3rd, Griggs RC, Brooke MH, Miller JP, Pestronk A, Robison J, King W, Signore L, et al. A comparison of daily and alternate-day prednisone therapy in the treatment of Duchenne muscular dystrophy. Arch Neurol. 1991 Jun;48(6):575-9. doi: 10.1001/archneur.1991.00530180027012.
citation: Follmann D. Multivariate tests for multiple endpoints in clinical trials. Stat Med. 1995 Jun 15;14(11):1163-75. doi: 10.1002/sim.4780141103.
citation: Griggs RC, Moxley RT 3rd, Mendell JR, Fenichel GM, Brooke MH, Pestronk A, Miller JP, Cwik VA, Pandya S, Robison J, et al. Duchenne dystrophy: randomized, controlled trial of prednisone (18 months) and azathioprine (12 months). Neurology. 1993 Mar;43(3 Pt 1):520-7. doi: 10.1212/wnl.43.3_part_1.520.
citation: Griggs RC, Moxley RT 3rd, Mendell JR, Fenichel GM, Brooke MH, Pestronk A, Miller JP. Prednisone in Duchenne dystrophy. A randomized, controlled trial defining the time course and dose response. Clinical Investigation of Duchenne Dystrophy Group. Arch Neurol. 1991 Apr;48(4):383-8. doi: 10.1001/archneur.1991.00530160047012.
citation: Hinton VJ, Nereo NE, Fee RJ, Cyrulnik SE. Social behavior problems in boys with Duchenne muscular dystrophy. J Dev Behav Pediatr. 2006 Dec;27(6):470-6. doi: 10.1097/00004703-200612000-00003.
citation: Hopke PK, Liu C, Rubin DB. Multiple imputation for multivariate data with missing and below-threshold measurements: time-series concentrations of pollutants in the Arctic. Biometrics. 2001 Mar;57(1):22-33. doi: 10.1111/j.0006-341x.2001.00022.x.
citation: Kinali M, Mercuri E, Main M, Muntoni F, Dubowitz V. An effective, low-dosage, intermittent schedule of prednisolone in the long-term treatment of early cases of Duchenne dystrophy. Neuromuscul Disord. 2002 Oct;12 Suppl 1:S169-74. doi: 10.1016/s0960-8966(02)00097-4.
citation: Lippuner K, Casez JP, Horber FF, Jaeger P. Effects of deflazacort versus prednisone on bone mass, body composition, and lipid profile: a randomized, double blind study in kidney transplant patients. J Clin Endocrinol Metab. 1998 Nov;83(11):3795-802. doi: 10.1210/jcem.83.11.5235.
citation: Little R, Yau L. Intent-to-treat analysis for longitudinal studies with drop-outs. Biometrics. 1996 Dec;52(4):1324-33.
citation: Loftus J, Allen R, Hesp R, David J, Reid DM, Wright DJ, Green JR, Reeve J, Ansell BM, Woo PM. Randomized, double-blind trial of deflazacort versus prednisone in juvenile chronic (or rheumatoid) arthritis: a relatively bone-sparing effect of deflazacort. Pediatrics. 1991 Sep;88(3):428-36.
citation: Lunceford JK, Davidian M. Stratification and weighting via the propensity score in estimation of causal treatment effects: a comparative study. Stat Med. 2004 Oct 15;23(19):2937-60. doi: 10.1002/sim.1903.
citation: Manzur AY, Kuntzer T, Pike M, Swan A. Glucocorticoid corticosteroids for Duchenne muscular dystrophy. Cochrane Database Syst Rev. 2004;(2):CD003725. doi: 10.1002/14651858.CD003725.pub2.
citation: Markham A, Bryson HM. Deflazacort. A review of its pharmacological properties and therapeutic efficacy. Drugs. 1995 Aug;50(2):317-33. doi: 10.2165/00003495-199550020-00008.
citation: Markham LW, Spicer RL, Khoury PR, Wong BL, Mathews KD, Cripe LH. Steroid therapy and cardiac function in Duchenne muscular dystrophy. Pediatr Cardiol. 2005 Nov-Dec;26(6):768-71. doi: 10.1007/s00246-005-0909-4.
citation: Mayhew A, Cano S, Scott E, Eagle M, Bushby K, Muntoni F; North Star Clinical Network for Paediatric Neuromuscular Disease. Moving towards meaningful measurement: Rasch analysis of the North Star Ambulatory Assessment in Duchenne muscular dystrophy. Dev Med Child Neurol. 2011 Jun;53(6):535-42. doi: 10.1111/j.1469-8749.2011.03939.x. Epub 2011 Mar 17.
citation: Mendell JR, Moxley RT, Griggs RC, Brooke MH, Fenichel GM, Miller JP, King W, Signore L, Pandya S, Florence J, et al. Randomized, double-blind six-month trial of prednisone in Duchenne's muscular dystrophy. N Engl J Med. 1989 Jun 15;320(24):1592-7. doi: 10.1056/NEJM198906153202405.
citation: Merlini L, Cicognani A, Malaspina E, Gennari M, Gnudi S, Talim B, Franzoni E. Early prednisone treatment in Duchenne muscular dystrophy. Muscle Nerve. 2003 Feb;27(2):222-7. doi: 10.1002/mus.10319.
citation: Moxley RT 3rd, Ashwal S, Pandya S, Connolly A, Florence J, Mathews K, Baumbach L, McDonald C, Sussman M, Wade C; Quality Standards Subcommittee of the American Academy of Neurology; Practice Committee of the Child Neurology Society. Practice parameter: corticosteroid treatment of Duchenne dystrophy [RETIRED]: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2005 Jan 11;64(1):13-20. doi: 10.1212/01.WNL.0000148485.00049.B7.
citation: O'Brien PC. Procedures for comparing samples with multiple endpoints. Biometrics. 1984 Dec;40(4):1079-87.
citation: Phillips MF, Quinlivan RC, Edwards RH, Calverley PM. Changes in spirometry over time as a prognostic marker in patients with Duchenne muscular dystrophy. Am J Respir Crit Care Med. 2001 Dec 15;164(12):2191-4. doi: 10.1164/ajrccm.164.12.2103052.
citation: Pocock SJ, Geller NL, Tsiatis AA. The analysis of multiple endpoints in clinical trials. Biometrics. 1987 Sep;43(3):487-98.
citation: Quinlivan R, Roper H, Davie M, Shaw NJ, McDonagh J, Bushby K. Report of a Muscular Dystrophy Campaign funded workshop Birmingham, UK, January 16th 2004. Osteoporosis in Duchenne muscular dystrophy; its prevalence, treatment and prevention. Neuromuscul Disord. 2005 Jan;15(1):72-9. doi: 10.1016/j.nmd.2004.09.009. Epub 2004 Dec 10. No abstract available.
citation: Reitter B. Deflazacort vs. prednisone in Duchenne muscular dystrophy: trends of an ongoing study. Brain Dev. 1995;17 Suppl:39-43.
citation: Sansome A, Royston P, Dubowitz V. Steroids in Duchenne muscular dystrophy; pilot study of a new low-dosage schedule. Neuromuscul Disord. 1993 Sep-Nov;3(5-6):567-9. doi: 10.1016/0960-8966(93)90117-3.
citation: Silversides CK, Webb GD, Harris VA, Biggar DW. Effects of deflazacort on left ventricular function in patients with Duchenne muscular dystrophy. Am J Cardiol. 2003 Mar 15;91(6):769-72. doi: 10.1016/s0002-9149(02)03429-x. No abstract available.
citation: Simonds AK, Muntoni F, Heather S, Fielding S. Impact of nasal ventilation on survival in hypercapnic Duchenne muscular dystrophy. Thorax. 1998 Nov;53(11):949-52. doi: 10.1136/thx.53.11.949.
citation: Stein RE, Jessop DJ. Functional status II(R). A measure of child health status. Med Care. 1990 Nov;28(11):1041-55. doi: 10.1097/00005650-199011000-00006.
citation: Tang DI, Geller NL, Pocock SJ. On the design and analysis of randomized clinical trials with multiple endpoints. Biometrics. 1993 Mar;49(1):23-30.
citation: Varni JW, Seid M, Knight TS, Uzark K, Szer IS. The PedsQL 4.0 Generic Core Scales: sensitivity, responsiveness, and impact on clinical decision-making. J Behav Med. 2002 Apr;25(2):175-93. doi: 10.1023/a:1014836921812.
citation: Varni JW, Seid M, Kurtin PS. PedsQL 4.0: reliability and validity of the Pediatric Quality of Life Inventory version 4.0 generic core scales in healthy and patient populations. Med Care. 2001 Aug;39(8):800-12. doi: 10.1097/00005650-200108000-00006.
citation: Varni JW, Seid M, Rode CA. The PedsQL: measurement model for the pediatric quality of life inventory. Med Care. 1999 Feb;37(2):126-39. doi: 10.1097/00005650-199902000-00003.
citation: Witt WP, Kasper JD, Riley AW. Mental health services use among school-aged children with disabilities: the role of sociodemographics, functional limitations, family burdens, and care coordination. Health Serv Res. 2003 Dec;38(6 Pt 1):1441-66. doi: 10.1111/j.1475-6773.2003.00187.x.
citation: Xie H, Heitjan DF. Sensitivity analysis of causal inference in a clinical trial subject to crossover. Clin Trials. 2004 Feb;1(1):21-30. doi: 10.1191/1740774504cn005oa.
citation: Guglieri M, Bushby K, McDermott MP, Hart KA, Tawil R, Martens WB, Herr BE, McColl E, Speed C, Wilkinson J, Kirschner J, King WM, Eagle M, Brown MW, Willis T, Griggs RC; FOR-DMD Investigators of the Muscle Study Group; Straub V, van Ruiten H, Childs AM, Ciafaloni E, Shieh PB, Spinty S, Maggi L, Baranello G, Butterfield RJ, Horrocks IA, Roper H, Alhaswani Z, Flanigan KM, Kuntz NL, Manzur A, Darras BT, Kang PB, Morrison L, Krzesniak-Swinarska M, Mah JK, Mongini TE, Ricci F, von der Hagen M, Finkel RS, O'Reardon K, Wicklund M, Kumar A, McDonald CM, Han JJ, Joyce N, Henricson EK, Schara-Schmidt U, Gangfuss A, Wilichowski E, Barohn RJ, Statland JM, Campbell C, Vita G, Vita GL, Howard JF Jr, Hughes I, McMillan HJ, Pegoraro E, Bello L, Burnette WB, Thangarajh M, Chang T. Effect of Different Corticosteroid Dosing Regimens on Clinical Outcomes in Boys With Duchenne Muscular Dystrophy: A Randomized Clinical Trial. JAMA. 2022 Apr 19;327(15):1456-1468. doi: 10.1001/jama.2022.4315.