Developed through an initiative co-led by NBDF, coreHEM Mental Health Outlook questionnaire (coreHEM-MHO) is a patient-reported outcome measurement (PROM) instrument that assesses mental health outlook (including psychological status and emotional functioning) associated with receiving gene therapy or any durable treatment for hemophilia.
The coreHEM-MHO instrument is owned by NBDF and available for use in research and within clinical trial settings through a license agreement. Certified translations are available for multiple countries and languages. coreHEM-MHO has been content validated for use in men and adolescents 15 years or older who have hemophilia. It is recommended that coreHEM-MHO be used at baseline and at periodic timepoints after dosing.
coreHEM-MHO consists of 26 questions in two parts. The first 20 questions are suitable regardless of treatment therapy. The additional 6 questions are specific for those considering or who have been treated with gene therapy.
In 2017, the National Bleeding Disorders Foundation, the Center for Medical Technology Policy and McMaster University partnered to develop a core outcome set (COS) for gene therapy in hemophilia. The aim of the coreHEM project was to determine the set of outcome measures required to evaluate efficacy, safety, comparative effectiveness, and value of gene therapy for hemophilia.
The coreHEM project was a multi-stakeholder initiative that prioritized a list of outcomes that are recommended for use in all clinical trials for gene therapy for hemophilia. coreHEM utilized a modified Delphi consensus process, based on methods adapted from the Core Outcome Measures in Effectiveness Trials (COMET) Initiative and involved forty- nine participants (five patients, five clinicians, five researchers, four regulators, three research agencies, six health technology assessors, nine payers, and twelve drug developers). The involvement of lived experience experts (LEEs, aka patients) ensured that selected outcomes were meaningful and relevant to persons living with hemophilia. In addition to regulatory-mandated adverse effects, six outcomes were identified as the COS and include: bleed frequency, factor activity level, duration of expression, chronic pain, healthcare resource use, and mental health outlook.
While the unique impact of gene therapy on the mental health outlook of persons with hemophilia was recognized as an important outcome, at that time, there were no patient-reported outcome measurement (PROM) instruments to sufficiently measure it. Subsequently, the coreHEM Mental Health Outlook Initiative was created and tasked with developing such tool. coreHEM-MHO is a content validated PROM instrument used to assess the mental health outlook associated with receiving gene therapy or any durable treatment for hemophilia.
coreHEM-MHO is used to assess the mental health outlook associated with receiving gene therapy or any durable treatment for hemophilia in men 15 years and older. coreHEM defines Mental Health Outcome as “A person’s psychological status; whether a person has positive feelings (joy, excitement, ease of living, new outlook on life) or negative feelings (anxiety, depression, fear, and uncertainty) associated with having hemophilia, or the treatment of hemophilia.”
coreHEM-MHO is a content-validated patient-reported outcome measure (PROM) instrument appropriate for use as an exploratory endpoint in clinical trials, for research in the clinical setting, and longitudinally in registries and long-term follow-up studies. It can be used to support value assessment and to inform market access and other post-regulatory decisions.
coreHEM MHO asks questions about mental health aligned within five domains: stigma, anxiety, depression, life interference, and identity. There are two sections: the first section can be used for people on any treatment for hemophilia and contains 20 questions about the mental health impact of living with and treating hemophilia. The second section is gene-therapy specific. This section contains 6 questions and should be included in studies where participants have had or are going to receive gene therapy. The two sections are scored separately. Both sections are scored from 0 to 1, where a score closer to 1 indicates a better mental health outlook.
When used in a study or trial, it is recommended that coreHEM MHO is administered at baseline (before gene therapy infusion or before a treatment change), and then again, every three months for the first year. After the one-year follow-up, it is recommended to be taken yearly. Scores from different time points can be compared to demonstrate changes in mental health outlook.
coreHEM-MH is owned by NBDF and available for use through a license agreement. It has been translated into 20 languages.
- Iorio A, Skinner MW, Clearfield E, Messner D, Pierce GF, Witkop M, Tunis S. Core outcome set for gene therapy in haemophilia: Results of the coreHEM multistakeholder project. Haemophilia. 2018;24(4):e167-e172.
- Skinner MW, Clearfield E, Iorio A, Tunis S. Comparing Outcomes Across Clinical Trials: Core Outcome Set for Hemophilia Gene Therapy as a Model for Other Diseases. DIA Global Forum. 2017;9(5).
- Clearfield E, Chang HY, Messner D, Valentino LA, Skinner M. PCR45 Development of a Patient-Reported Outcome Measure (PROM) to Fully Report a Proposed Core Outcome Set. Value in Health. 2022;25(7 Supplement):S549.
- Clearfield E, Chang H-Y, Majid T, Skinner MW. Responses to Anxiety and Depression Items in People with Hemophilia who Tested a Patient Reported Outcome Measure: The coreHEM MH Study. Res Pract Thromb Haemost. 2021;5(Suppl 2).
- Clearfield E, Janssen EM, Witkop M, Hayes B, Skinner MW. Developing a patient reported outcome measure to explore mental health outlook in people with Hemophilia: Development of a conceptual framework. Haemophilia. 2020;26(S4):62.
- Clearfield E, Al Naber J, Tunis S, Messner D. OP163 Health Technology Assessment Participation And Prioritization In Core Outcome Set Development. International Journal of Technology Assessment in Health Care. 2019;35(S1):35.
- Clearfield E, Messner D, Al Naber J, Tunis S. Discerning and promoting patient-important outcomes in the development of a core outcome set: Examples from coreHEM and coreNASH. Journal of Evidence-Based Medicine. 2019;12(S1):11.
- Clearfield E, Skinner M, Iorio A, Tunis S, Al Naber J, Messner D. PP93 HTA Role in coreHEM, a Multi-stakeholder Core Outcome Set Project. International Journal of Technology Assessment in Health Care. 2018;34(1):100-101.
- Tunis SR, Skinner MW, Clearfield E, Messner DA, Al Naber J, Iorio A. First Steps in Choosing Appropriate Instruments/Measurements for a Core Outcome Set: An Example from coreHEM. Value in Health. 2018;21(Supp 1):S212.
- Clearfield E, Tunis S, Messner D, Al Naber J, Iorio A, Skinner M. coreHEM: A multi-stakeholder approach to developing a core outcome set for gene therapy in hemophilia. Haemophilia. 2018;24(S5):81.
Scientific meetings - Podium presentations
Clearfield E, Korenjak M, Noone D, O’Hara J, Willemse J. Patient Participation in Core Outcome Set Development: Patient Experiences in coreHEM and coreNASH. HTAi Annual Meeting 2019. Panel Moderator. Cologne, Germany. June 2019.
Clearfield E, Al Naber J, Tunis S, Messner D. Health Technology Assessment Participation and Prioritization in Core Outcome Set Development. HTAi Annual Meeting 2019. Podium Presentation. Cologne, Germany. June 2019.
Tunis, S, Skinner MW, Iorio A, Clearfield E, Pezalla E, Werko S, Jain M. Core Outcome Sets and HTA: coreHEM Defining Value Through Multi-Stakeholder Engagement. HTAi Annual Meeting 2018. Panel Presentation. Vancouver, BC. June 2018.
Scientific meetings - Poster presentations
Clearfield E, Chang HY, Messner D, Valentino LA, Skinner MW. Development of a Patient-Reported Outcome Measure (PROM) to Fully Report a Proposed Core Outcome Set. ISPOR 2022. Poster Presentation. Washington, DC. Poster May 2022.
Clearfield E, Chang HY, Majid T, Witkop ML, Skinner MW. coreHEM Mental Health PROM Development: Updating the Conceptual Framework as a Step in Content Validation. WFH 2022 World Congress. Poster Presentation. Montréal, Canada. May 2022.
Hayes B, Clearfield E, Chang HY. Knowledge and Attitudes Toward Gene Therapy for Hemophilia. Patient Perceptions: Findings from the coreHEM Mental Health Initiative. NHF's 73rd Bleeding Disorders Conference. Poster Presentation. Virtual. August 2021.
Clearfield E, Chang HY, Majid T, Skinner MW. Responses to Anxiety and Depression Items in People with Hemophilia Who Tested a Patient Reported Outcome Measure: The coreHEM MH Study. ISTH 2021 Virtual Congress. Poster Presentation. Virtual hosted from Philadelphia. July 2021.
Clearfield E, Janssen EM, Reed S, Chang HY, Witkop M, Skinner MW. A review of current patient reported outcome measures used to assess mental health in people with hemophilia. NHF's 72nd Bleeding Disorders Conference. Poster Presentation. Virtual. August 2020.
Clearfield E, Janssen EM, Witkop M, Hayes B, Skinner MW. Developing a patient reported outcome measure to explore mental health outlook in people with Hemophilia: Development of a conceptual framework. WFH Virtual Summit 2020. Poster Presentation. Virtual. June 2020.
Skinner MW, Iorio A, Tunis S, Clearfield E, Al Naber J, Messner D. coreHEM, a Multistakeholder Core Outcome Set Project for Gene Therapy in Hemophilia. ASGCT 22nd Annual Meeting. Poster Presentation. Washington, DC. April 2019.
Clearfield E, Al Naber J, Messner D, Tunis SR. Discerning and promoting patient-important outcomes in the development of a core outcome set: examples from coreHEM and coreNASH. COMET VII. Poster Presentation. Amsterdam, Netherlands. November 2018.
Clearfield E, Skinner MW, Iorio A, Tunis SR, Al Naber J, Messner D. HTA Role in coreHEM, a Multi-stakeholder Core Outcome Set Project. Poster Presentation. HTAi Annual Meeting. Vancouver, BC. June 2018.
Tunis SR, Skinner MW, Clearfield E, Messner D, Al Naber J, Iorio A. First steps in choosing appropriate instruments/measurements for a core outcome set: an example from coreHEM. Poster Presentation. ISPOR 2018. Baltimore, MD. May 2018.