Lupus Science and Medicine (May 2021)
Delivering clinical trials at home: protocol, design and implementation of a direct-to-family paediatric lupus trial
- Laura E Schanberg,
- S Canna,
- A Grom,
- E Mellins,
- A Brown,
- S Jones,
- E Baker,
- A Kemp,
- T Davis,
- S Jackson,
- K Jones,
- T Mason,
- A Hanson,
- J Jones,
- J Cooper,
- T Lee,
- J Chang,
- M Holland,
- S Joshi,
- L Lim,
- A Murphy,
- K Moore,
- B ferreira,
- S Li,
- P Lee,
- K Abulaban,
- R Agbayani,
- S Akoghlanian,
- E Anderson,
- L Barillas-Arias,
- K Baszis,
- M Becker,
- H Bell-Brunson,
- H Benham,
- S Benseler,
- T Beukelman,
- H Brunner,
- H Bukulmez,
- L Cerracchio,
- E Chalom,
- K Chundru,
- J Dean,
- F Dedeoglu,
- V Dempsey,
- J Drew,
- B Feldman,
- P Ferguson,
- C Fleming,
- L Franco,
- I Goh,
- D Goldsmith,
- B Gottlieb,
- T Graham,
- T Griffin,
- M Hance,
- K Hickey,
- M Hollander,
- J Hsu,
- A Huber,
- C Hung,
- A Huttenlocher,
- L Imundo,
- C Inman,
- J Jaquith,
- L Jung,
- D Kingsbury,
- K Klein,
- M Klein-Gitelman,
- S Kramer,
- S Lapidus,
- D Latham,
- B Malla,
- M Malloy,
- A Martyniuk,
- K McConnell,
- D McCurdy,
- C McMullen-Jackson,
- L Moorthy,
- E Muscal,
- S Kim,
- L Favier,
- S Morgan,
- A Jackson,
- L Marques,
- Stephen J Balevic,
- K Hayward,
- J Nicholas,
- D Lovell,
- J Harris,
- E Lawson,
- C Moss,
- N George,
- A Cooper,
- Rachel L Randell,
- M Adams,
- S Cooper,
- M Miller,
- C Black,
- M Mitchell,
- F De Benedetti,
- M Fox,
- K Kaufman,
- A Merritt,
- J Fuller,
- M Fitzgerald,
- A Davis,
- C Davis,
- L Henderson,
- S Mohan,
- Y Kimura,
- L Harel,
- R Laxer,
- K McCarthy,
- I Ferguson,
- E McCormick,
- A Hay,
- M Guzman,
- E Fox,
- P Hill,
- S McGuire,
- J Lam,
- J Boland,
- S Ballinger,
- E MENDOZA,
- J NOCTON,
- N Johnson,
- S Bowman,
- M Ibarra,
- S Hong,
- M Guevara,
- K James,
- A Adams,
- B DONALDSON,
- C Kremer,
- L Cannon,
- R Nicolai,
- M Freeman,
- D Levy,
- K Gerhold,
- A Insalaco,
- W Bernal,
- E Kessler,
- C Lin,
- M Lerman,
- T Hahn,
- Lindsay Singler,
- Anthony Cunningham,
- Michael Cohen-Wolkowiez,
- Christoph P Hornik,
- N Abel,
- J Aiello,
- C Alejandro,
- E Allenspach,
- R Alperin,
- M Alpizar,
- G Amarilyo,
- W Ambler,
- S Ardoin,
- S Armendariz,
- I Balboni,
- S Balevic,
- L Ballenger,
- N Balmuri,
- F Barbar-Smiley,
- M Basiaga,
- E Beltz,
- T Bigley,
- B Binstadt,
- M Blakley,
- J Bohnsack,
- A Boneparth,
- C Bracaglia,
- E Brooks,
- M Brothers,
- M Buckley,
- D Bullock,
- B Cameron,
- P Carper,
- V Cartwright,
- E Cassidy,
- A Chang-Hoftman,
- V Chauhan,
- P Chira,
- T Chinn,
- H Clairman,
- D Co,
- A Confair,
- H Conlon,
- R Connor,
- C Correll,
- R Corvalan,
- D Costanzo,
- R Cron,
- L Curiel-Duran,
- T Curington,
- M Curry,
- A Dalrymple,
- D De Ranieri,
- M De Guzman,
- N Delnay,
- E DeSantis,
- T Dickson,
- J Dingle,
- E Dorsey,
- S Dover,
- J Dowling,
- K Driest,
- Q Du,
- K Duarte,
- D Durkee,
- E Duverger,
- J Dvergsten,
- A Eberhard,
- M Eckert,
- K Ede,
- B Edelheit,
- C Edens,
- Y Edgerly,
- M Elder,
- B Ervin,
- S Fadrhonc,
- C Failing,
- D Fair,
- M Falcon,
- S Federici,
- J Fennell,
- R Ferrucho,
- K Fields,
- T Finkel,
- O Flynn,
- L Fogel,
- K Fritz,
- S Froese,
- R Fuhlbrigge,
- D Gerstbacher,
- M Gilbert,
- M Gillispie-Taylor,
- E Giverc,
- C Godiwala,
- H Goheer,
- E Gotschlich,
- A Gotte,
- C Gracia,
- S Grevich,
- J Griswold,
- P Guittar,
- M Hager,
- O Halyabar,
- E Hammelev,
- S Haro,
- O Harry,
- E Hartigan,
- J Hausmann,
- J Heiart,
- K Hekl,
- M Henrickson,
- A Hersh,
- S Hillyer,
- L Hiraki,
- M Hiskey,
- P Hobday,
- C Hoffart,
- M Horwitz,
- J Huggins,
- J HuiYuen,
- J Huntington,
- G Janow,
- S Jared,
- C Justice,
- A Justiniano,
- N Karan,
- U Khalsa,
- B Kienzle,
- M Kitcharoensakkul,
- T Klausmeier,
- B Kompelien,
- A Kosikowski,
- L Kovalick,
- J Kracker,
- J Lai,
- B Lang,
- B Lapin,
- A Lasky,
- L Lentini,
- S Lieberman,
- N Ling,
- M Lingis,
- M Lo,
- D Lowman,
- N Luca,
- S Lvovich,
- C Madison,
- J Madison,
- S Magni Manzoni,
- J Maller,
- M Mannion,
- C Manos,
- S Mathus,
- L McAllister,
- P McCurdy Stokes,
- I McHale,
- A McMonagle,
- E Meidan,
- R Mercado,
- L Michalowski,
- P Miettunen,
- D Milojevic,
- E Mirizio,
- E Misajon,
- R Modica,
- E Morgan Dewitt,
- T Moussa,
- V Mruk,
- R Nadler,
- B Nahal,
- K Nanda,
- N Nasah,
- L Nassi,
- S Nativ,
- M Natter,
- J Neely,
- B Nelson,
- L Newhall,
- L Ng,
- P Nigrovic,
- B Nolan,
- E Oberle,
- B Obispo
Affiliations
- Laura E Schanberg
- Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA
- S Canna
- A Grom
- E Mellins
- A Brown
- S Jones
- 5Cardiff and Vale University Health Board, Cardiff, UK
- E Baker
- A Kemp
- T Davis
- S Jackson
- 1Department of Paediatrics, University of Oxford, Oxford, UK
- K Jones
- T Mason
- A Hanson
- J Jones
- 15Neurological Surgery and Radiology, UAB, Birmingham, AL
- J Cooper
- T Lee
- 3Leeds Children’s Hospital, Leeds, UK
- J Chang
- M Holland
- S Joshi
- Royal Free Hospital NHS Foundation Trust, London, UK
- L Lim
- A Murphy
- 2University Hospitals of Leicester NHS Trust, Leicester, UK
- K Moore
- B ferreira
- Rheumatology, SARAH Network of Rehabilitation Hospitals, Brasíia, Brazil
- S Li
- Department of Rheumatology and Immunology, the Second Xiang Ya Hospital, Central South University, Changsha, Hunan, China, Changsha, China
- P Lee
- 3Southampton Clinical Trials Unit, University of Southampton, Southampton, UK
- K Abulaban
- R Agbayani
- S Akoghlanian
- E Anderson
- 1ISMH, University of Stirling, Stirling, UK
- L Barillas-Arias
- K Baszis
- M Becker
- 1Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland
- H Bell-Brunson
- H Benham
- S Benseler
- 2Alberta Children`s Hospital, Calgary, Canada
- T Beukelman
- H Brunner
- 3PRCSG, Cincinnati Children`s Hosp Med Ctr, Cincinnati, United States
- H Bukulmez
- L Cerracchio
- E Chalom
- 2PRCSG, Cincinnati Children`s Hospital Medical Center, Cincinnati, United States
- K Chundru
- J Dean
- F Dedeoglu
- V Dempsey
- J Drew
- B Feldman
- P Ferguson
- C Fleming
- L Franco
- 2Rheumatology, Center for Osteoarthritis, Caracas, Caracas, Venezuela, Bolivarian Republic Of
- I Goh
- D Goldsmith
- B Gottlieb
- T Graham
- T Griffin
- M Hance
- K Hickey
- M Hollander
- J Hsu
- 1Roche Innovation Ctr, New York, United States
- A Huber
- C Hung
- A Huttenlocher
- L Imundo
- C Inman
- J Jaquith
- L Jung
- D Kingsbury
- 2PRCSG, Cincinnati Children`s Hospital Medical Center, Cincinnati, United States
- K Klein
- 1University Hospital Zurich, Schlieren
- M Klein-Gitelman
- S Kramer
- S Lapidus
- D Latham
- B Malla
- M Malloy
- A Martyniuk
- K McConnell
- D McCurdy
- C McMullen-Jackson
- L Moorthy
- E Muscal
- S Kim
- Gilead sciences, Inc., Foster city, United States
- L Favier
- S Morgan
- A Jackson
- 3English Institute of Sport, Manchester, UK
- L Marques
- Stephen J Balevic
- Pediatric Rheumatology, Duke University, Durham, North Carolina, USA
- K Hayward
- J Nicholas
- D Lovell
- 3PRCSG, Cincinnati Children`s Hosp Med Ctr, Cincinnati, United States
- J Harris
- E Lawson
- C Moss
- N George
- A Cooper
- Royal Stoke University Hospital, Newcastle Under Lyme, UK
- Rachel L Randell
- Duke University School of Medicine, Durham, North Carolina, USA
- M Adams
- S Cooper
- 1Hampshire Hospitals NHS Foundation Trust, Winchester, UK
- M Miller
- 1Usher Institute, University of Edinburgh, Edinburgh, UK
- C Black
- 3Aberdeen Centre for Health Data Science, University of Aberdeen, Aberdeen, UK
- M Mitchell
- 15Aneurin Bevan University Health Board, Gwent, UK
- F De Benedetti
- Laboratorio di Reumatologia, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy
- M Fox
- K Kaufman
- A Merritt
- J Fuller
- M Fitzgerald
- A Davis
- 2University of Bath, Bath
- C Davis
- Somerset NHS Foundation Trust, Taunton, UK
- L Henderson
- 1Royal Brompton Hospital, part of Guys and St Thomas, London, UK
- S Mohan
- Genentech, Inc., South San Francisco, CA, United States
- Y Kimura
- 7Hackensack U Med Ctr, Hackensack
- L Harel
- 1Hamburg Center for Pediatric Rheumatology, Hamburg
- R Laxer
- 7University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada
- K McCarthy
- I Ferguson
- E McCormick
- A Hay
- M Guzman
- E Fox
- P Hill
- S McGuire
- J Lam
- Guy’s Severe Asthma Centre, Guy’s and St Thomas’ NHS Trust, London, UK
- J Boland
- S Ballinger
- E MENDOZA
- J NOCTON
- N Johnson
- S Bowman
- 5University Hospital Birmingham, Birmingham
- M Ibarra
- S Hong
- 2Division of Rheumatology, University of Ulsan College of Medicine, Asan Medical Center
- M Guevara
- K James
- 4School of Computing Science, Newcastle University, Newcastle Upon Tyne
- A Adams
- B DONALDSON
- C Kremer
- L Cannon
- R Nicolai
- M Freeman
- D Levy
- K Gerhold
- A Insalaco
- W Bernal
- E Kessler
- C Lin
- 3Genentech, San Francisco, United States
- M Lerman
- T Hahn
- Lindsay Singler
- Pediatrics, Duke Clinical Research Institute, Durham, North Carolina, USA
- Anthony Cunningham
- Pediatrics, Duke Clinical Research Institute, Durham, North Carolina, USA
- Michael Cohen-Wolkowiez
- Duke Clinical Research Institute, Durham, North Carolina, USA
- Christoph P Hornik
- Duke Clinical Research Institute, Durham, North Carolina, USA
- N Abel
- J Aiello
- C Alejandro
- E Allenspach
- R Alperin
- M Alpizar
- G Amarilyo
- W Ambler
- S Ardoin
- 1Rheumatology and Immunology
- S Armendariz
- I Balboni
- S Balevic
- L Ballenger
- N Balmuri
- F Barbar-Smiley
- M Basiaga
- E Beltz
- T Bigley
- B Binstadt
- M Blakley
- 5Indiana University, Indianapolis, United States
- J Bohnsack
- 2PRCSG, Cincinnati Children`s Hospital Medical Center, Cincinnati, United States
- A Boneparth
- C Bracaglia
- E Brooks
- M Brothers
- M Buckley
- D Bullock
- B Cameron
- P Carper
- V Cartwright
- E Cassidy
- A Chang-Hoftman
- V Chauhan
- P Chira
- T Chinn
- H Clairman
- D Co
- A Confair
- H Conlon
- R Connor
- C Correll
- R Corvalan
- D Costanzo
- R Cron
- L Curiel-Duran
- T Curington
- M Curry
- A Dalrymple
- D De Ranieri
- M De Guzman
- N Delnay
- E DeSantis
- T Dickson
- J Dingle
- E Dorsey
- S Dover
- J Dowling
- K Driest
- Q Du
- K Duarte
- D Durkee
- E Duverger
- J Dvergsten
- A Eberhard
- M Eckert
- K Ede
- B Edelheit
- C Edens
- Y Edgerly
- M Elder
- B Ervin
- S Fadrhonc
- C Failing
- D Fair
- M Falcon
- Hospital Virgen del Rocío, Pharmacy Department, Seville, Spain
- S Federici
- J Fennell
- R Ferrucho
- K Fields
- T Finkel
- O Flynn
- L Fogel
- K Fritz
- S Froese
- R Fuhlbrigge
- D Gerstbacher
- M Gilbert
- M Gillispie-Taylor
- E Giverc
- C Godiwala
- H Goheer
- E Gotschlich
- A Gotte
- C Gracia
- S Grevich
- 2Pediatric Rheumatology, Seattle Children`s Hospital, Department of Pediatrics, University of Washington
- J Griswold
- P Guittar
- M Hager
- O Halyabar
- E Hammelev
- S Haro
- O Harry
- E Hartigan
- J Hausmann
- J Heiart
- K Hekl
- M Henrickson
- 3PRCSG, Cincinnati Children`s Hosp Med Ctr, Cincinnati, United States
- A Hersh
- S Hillyer
- L Hiraki
- M Hiskey
- P Hobday
- C Hoffart
- M Horwitz
- J Huggins
- J HuiYuen
- J Huntington
- G Janow
- S Jared
- C Justice
- A Justiniano
- N Karan
- U Khalsa
- B Kienzle
- M Kitcharoensakkul
- T Klausmeier
- B Kompelien
- A Kosikowski
- L Kovalick
- J Kracker
- J Lai
- B Lang
- B Lapin
- A Lasky
- L Lentini
- S Lieberman
- N Ling
- M Lingis
- M Lo
- D Lowman
- N Luca
- S Lvovich
- C Madison
- J Madison
- S Magni Manzoni
- J Maller
- M Mannion
- C Manos
- S Mathus
- L McAllister
- P McCurdy Stokes
- I McHale
- A McMonagle
- Southern Health and Social Care Trust, UK
- E Meidan
- R Mercado
- L Michalowski
- P Miettunen
- D Milojevic
- 8Tufts Med Ctr, Boston
- E Mirizio
- E Misajon
- R Modica
- E Morgan Dewitt
- T Moussa
- V Mruk
- R Nadler
- 1 Medical Corps, Surgeon General’s Headquarters, Israel Defense Forces, Ramat Gan, Israel
- B Nahal
- K Nanda
- 2PRCSG, Cincinnati Children`s Hospital Medical Center, Cincinnati, United States
- N Nasah
- L Nassi
- S Nativ
- M Natter
- J Neely
- B Nelson
- L Newhall
- L Ng
- P Nigrovic
- B Nolan
- E Oberle
- B Obispo
- DOI
- https://doi.org/10.1136/lupus-2021-000494
- Journal volume & issue
-
Vol. 8,
no. 1
Abstract
Introduction Direct-to-family clinical trials efficiently provide data while reducing the participation burden for children and their families. Although these trials can offer significant advantages over traditional clinical trials, the process of designing and implementing direct-to-family studies is poorly defined, especially in children with rheumatic disease. This paper provides lessons learnt from the design and implementation of a self-controlled, direct-to-family pilot trial aimed to evaluate the effects of a medication management device on adherence to hydroxychloroquine in paediatric SLE.Methods Several design features accommodate a direct-to-family approach. Participants meeting eligibility criteria from across the USA were identified a priori through a disease registry, and all outcome data are collected remotely. The primary outcome (medication adherence) is evaluated using electronic medication event-monitoring, plasma drug levels, patient questionnaires and pill counts. Secondary and exploratory endpoints include (1) lupus disease activity measured by a remote SLE Disease Activity Index examination and the Systemic Lupus Activity Questionnaire; and (2) hydroxychloroquine pharmacokinetics and pharmacodynamics. Recruitment of the initial target of 20 participants was achieved within 10 days. Due to initial recruitment success, enrolment was increased to 26 participants. Additional participants who were interested were placed on a waiting list in case of dropouts during the study.Discussion and dissemination Direct-to-family trials offer several advantages but present unique challenges. Lessons learnt from the protocol development, design, and implementation of this trial will inform future direct-to-family trials for children and adults with rheumatic diseases. Additionally, the data collected remotely in this trial will provide critical information regarding the accuracy of teleresearch in lupus, the impact of adherence to hydroxychloroquine on disease activity and a pharmacokinetic analysis to inform paediatric-specific dosing of hydroxychloroquine.Trial registration number ClinicalTrials.gov Registry (NCT04358302).