Background: Creatine transporter deficiency (CTD) and guanidinoacetate methyltransferase (GAMT) deficiency are rare inborn errors of creatine metabolism, resulting in cerebral creatine deficiency syndromes that alter energy metabolism. There is currently no approved treatment for CTD, while the current management for GAMT deficiency requires lifelong treatment with restricted diet and intake of high amounts of oral supplements. Efforts to develop effective, sustainable treatments for these conditions are ongoing. Implementing clinical trials in rare diseases can be challenging due to the small populations and extreme heterogeneity of phenotypes. Additionally, patient and caregiver perspectives have historically been overlooked in the development of treatments, which may limit the inclusion of outcome measures that are meaningful to patients. Therefore, the Association for Creatine Deficiencies (ACD) partnered with caregivers and health professionals to develop a COS for CTD and GAMT deficiency to help overcome these challenges during clinical trials for these conditions.
Methods: To gather medically relevant and patient-meaningful outcomes, we conducted literature reviews and patient/caregiver focus groups. Additionally, we reviewed patient meaningful outcome survey data shared by the CreatineInfo Patient Registry. Our consensus process was a multifaceted approach that involved three community-wide online Delphi surveys, followed by an in-person consensus workshop attended by a diverse group of caregivers and health professionals to finalize the COS. Caregivers led this project, received training and education about COS and clinical trial research, and were partners throughout the COS development process.
Results: We used a multistakeholder, consensus-driven approach to develop a COS of eight outcomes for CTD and GAMT deficiency. Our approach to caregiver training and partnership helped caregivers to think critically about their child(ren) and the candidate outcomes, which facilitated prioritization of the most important outcomes. Moreover, our approach fostered active discussions with health professionals during the consensus workshop, expediting the selection of the final COS.
Conclusions: We established the first known COS for CTD and GAMT deficiency which includes eight outcomes that are important to patients, caregivers, and health professionals and should be measured in every CTD and GAMT deficiency clinical trial.
Note: We searched the COMET database and did not identify any published or ongoing COS development projects for CTD and/or GAMT deficiency.
Zahra Nasseri Moghaddam, Emily Reinhardt, Audrey Thurm, Beth Potter, Maureen Smith, Celeste Graham, Beth Tiller, Saadet Andrews, Amanda Atkins, Steven Baker, Deborah Bilder, Regina Bogar, Jacob Britz, Rachel Cafferty, Dan Coller, Ton deGrauw, Vicky Hall, Gerald S. Lipshutz, Nicola Longo, Judi Miller, Marzia Pasquali, Beth Robinson, Gajja Salomons, Andreas Schulze, Celine Weaton, Kayla Williams, Sarah Young, Jasmine Li, Laura Trutoiu, Sofia Balog, Terry Selucky, Sylvia Stockler, Heidi Wallis (P.I.)
Disease Category: Endocrine & metabolic
Disease Name: Creatine transporter deficiency (CTD), Guanidinoacetate methyltransferase (GAMT) deficiency, Cerebral creatine deficiency syndromes (CCDS)
Age Range: 0 - 100
Sex: Either
Nature of Intervention: Any
- Clinical experts
- Consumers (caregivers)
- Consumers (patients)
- Families
- Methodologists
- Patient/ support group representatives
- Researchers
- Service providers
- Service users
- Statisticians
- COS for clinical trials or clinical research
- COS for practice
- Consensus meeting
- Delphi process
- Focus group(s)
- Literature review
- Nominal group technique (NGT)
- Survey
To gather medically relevant and patient-meaningful outcomes, we conducted literature reviews and patient/caregiver focus groups. Additionally, we reviewed patient meaningful outcome survey data shared by the CreatineInfo Patient Registry. Our consensus process was a multifaceted approach that involved three community-wide online Delphi surveys, followed by an in-person consensus workshop attended by a diverse group of caregivers and health professionals to finalize the COS. Caregivers led this project, received training and education about COS and clinical trial research, and were partners throughout the COS development process.