Skip to main content
SpringerLink
Log in

Assessing the impact of non-severe hypoglycemic events and treatment in adults: development of the Treatment-Related Impact Measure—Non-severe Hypoglycemic Events (TRIM-HYPO)

  • Published:
Quality of Life Research Aims and scope Submit manuscript

Abstract

Purpose

Non-severe hypoglycemic events (NSHEs) are commonly experienced by diabetes patients, particularly among insulin users, and can have serious impacts on daily functioning, emotional well-being, sleep, work productivity, and treatment adherence. Currently, no PRO measures are available to assess the impacts of non-severe hypoglycemia. To address this gap, the Treatment-Related Impact Measure-Non-severe Hypoglycemic Events (TRIM-HYPO) was developed. This paper describes the TRIM-HYPO development and validation.

Methods

The creation of the TRIM-HYPO followed FDA’s guideline for PRO development. Concept elicitation data were gathered from literature review, clinical expert interviews, and focus groups of patients with Type 1 or 2 diabetes in four countries. Based on the qualitative analysis, draft items were generated and cognitively debriefed. Psychometric validation included factor analysis, item response theory analysis, and assessment of psychometric characteristics for the TRIM-HYPO.

Results

Eight clinical experts and 167 patients participated in concept elicitation. The validation study included 407 patients. Thirteen of the 46 items from the preliminary measure were dropped due to ceiling/floor effects and high correlations between conceptually similar items. Factor analysis confirmed five domains in the TRIM-HYPO: daily function, emotional well-being, diabetes management, sleep disruption, and work productivity. All scores were internally consistent (0.86–0.95) and reproducible with a test–retest range of 0.75–0.98. All but one a priori hypothesized associations for validity were confirmed.

Conclusions

Study findings demonstrate that the final, 33-item TRIM-HYPO is reliable and valid and may be useful for assessing impacts related to NSHEs in research and clinical practice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Workgroup on Hypoglycemia, American Diabetes Association. (2005). Defining and reporting hypoglycemia in diabetes: A report from the American Diabetes Association Workgroup on hypoglycemia. Diabetes Care, 28(5), 1245–1249.

    Article  Google Scholar 

  2. Kovatchev, B., Cox, D., Farhy, L., Straume, M., Gonder-Frederick, L., & Clarke, W. (2000). Episodes of severe hypoglycemia in type 1 diabetes are preceded and followed within 48 hours by measurable disturbances in blood glucose. The Journal of Clinical Endocrinolgy and Metabolism, 85(11), 4287–4292.

    CAS  Google Scholar 

  3. Brod, M., Christensen, T., Thomsen, T., & Bushnell, D. (2011). The impact of non-severe hypoglycemic events on work productivity and diabetes management. Value in Health, 14(5), 665–671.

    Article  PubMed  Google Scholar 

  4. Davis, R., Morrissey, M., Peters, J., Wittrup-Jensen, K., Kennedy-Martin, T., & Currie, C. (2005). Impact of hypoglycaemia on quality of life and productivity in type 1 and type 2 diabetes. Current Medical Research and Opinion, 21(9), 1477–1483.

    Article  PubMed  Google Scholar 

  5. Miller, C. D., Phillips, L. S., Ziemer, D. C., Gallina, D. L., Cook, C. B., & El-Kebbi, I. M. (2001). Hypoglycemia in patients with type 2 diabetes mellitus. Archives of Internal Medicine, 161(13), 1653–1659. doi:10.1001/archinte.161.13.1653.

    Article  CAS  PubMed  Google Scholar 

  6. Vexiau, P., Mavros, P., Krishnarajah, G., Lyu, R., & Yin, D. (2008). Hypoglycaemia in patients with type 2 diabetes treated with a combination of metformin and sulphonylurea therapy in France. Diabetes, Obesity & Metabolism, 10, 16–24. doi:10.1111/j.1463-1326.2008.00883.x.

    Article  Google Scholar 

  7. Unger, J. (2012). Uncovering undetected hypoglycemic events. Diabetes, Metabolic Syndrome and Obesity, 5, 57–74.

  8. Brod, M., Wolden, M., Christensen, T., & Bushnell, D. M. (2013). A nine country study of the burden of non-severe nocturnal hypoglycaemic events on diabetes management and daily function. Diabetes, Obesity & Metabolism, 15(6), 546–557. doi:10.1111/dom.12070.

    Article  CAS  Google Scholar 

  9. Brod, M., Christensen, T., & Bushnell, D. M. (2012). The impact of non-severe hypoglycemic events on daytime function and diabetes management among adults with type 1 and type 2 diabetes. Journal of Medical Economics, 15(5), 869–877. doi:10.3111/13696998.2012.686465.

    Article  PubMed  Google Scholar 

  10. El Achhab, Y., Nejjari, C., Chikri, M., & Lyoussi, B. (2008). Disease-specific health-related quality of life instruments among adults diabetic: A systematic review. Diabetes Research and Clinical Practice, 80(2), 171–184. doi:10.1016/j.diabres.2007.12.020.

    Article  PubMed  Google Scholar 

  11. Cox, D. J., Irvine, A., Gonder-Frederick, L., Nowacek, G., & Butterfield, J. (1987). Fear of hypoglycemia: Quantification, validation, and utilization. Diabetes Care, 10(5), 617–621. doi:10.2337/diacare.10.5.617.

    Article  CAS  PubMed  Google Scholar 

  12. Anarte Ortiz, M. T., Caballero, F. F., Ruiz de Adana, M. S., Rondán, R. M., Carreira, M., Domínguez-López, M., et al. (2011). Development of a new Fear of Hypoglycemia Scale: FH-15. Psychological Assessment, 23(2), 398–405. doi:10.1037/a0021927.

    Article  PubMed  Google Scholar 

  13. US Department of Health and Human Services (2009). Guidance for industry: Patient-reported outcomes measures: Use in medical product development to support labeling claims. http://www.fda.gov/downloads/Drugs/Guidances/UCM193282.pdf

  14. Brod, M., Tesler, L., & Christensen, T. (2009). Qualitative research and content validity: Developing best practices based on science and experience. Quality of Life Research, 18(9), 1263–1278. doi:10.1007/s11136-009-9540-9.

    Article  PubMed  Google Scholar 

  15. Sheehan, D. (1983). The anxiety disease. New York, NY: Charles Scribner and Sons.

    Google Scholar 

  16. Dupuy, H. (1984). The psychological general well-being (PGWB) index. In N. Wenger, M. Mattson, C. Furburg, & J. Elinson (Eds.), Assessment of quality of life in clinical trials of cardiovascular therapies (pp. 170–183). New York: Le Jacq Publishing.

    Google Scholar 

  17. Hays, R., & Stewart, A. (1992). Sleep Measures. In A. Stewart & J. Ware (Eds.), Measuring functioning and well-being: The medical outcomes study approach (pp. 235–259). Durham, NC: Duke University Press.

    Google Scholar 

  18. Wild, D., Clayson, D., Keating, K., & Gondek, K. (2005). Validation of a patient-administered questionnaire to measure the activity impairment experienced by women with uncomplicated urinary tract infection: The Activity Impairment Assessment (AIA). Health and Quality of Life Outcomes, 3, 42.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Reilly, M., Zbrozek, A., & Dukes, E. (1993). The validity and reproducibility of a work productivity and activity impairment instrument. Pharmacoeconomics, 4(5), 353–365.

    Article  CAS  PubMed  Google Scholar 

  20. Anderson, R. T., Skovlund, S. E., Marrero, D., Levine, D. N., Meadows, K., Brod, M., et al. (2004). Development and validation of the insulin treatment satisfaction questionnaire. Clinical Therapeutics, 26(4), 565–578.

    Article  PubMed  Google Scholar 

  21. Russell, D. (1996). UCLA Loneliness Scale (Version 3): Reliability, validity, and factor structure. Journal of Personality Assessment, 66(1), 20–40.

    Article  CAS  PubMed  Google Scholar 

  22. Hann, D. M., Jacobsen, P. B., Azzarello, L. M., Martin, S. C., Curran, S. L., Fields, K. K., et al. (1998). Measurement of fatigue in cancer patients: Development and validation of the Fatigue Symptom Inventory. Quality of Life Research, 7(4), 301–310.

    Article  CAS  PubMed  Google Scholar 

  23. Endicott, J., Nee, J., Harrison, W., & Blumenthal, R. (1993). Quality of Life Enjoyment and Satisfaction Questionnaire: A new measure. Psychopharmacology Bull, 29(2), 321–326.

    CAS  Google Scholar 

  24. Atkinson, M. J., Kumar, R., Cappelleri, J. C., & Hass, S. L. (2005). Hierarchical construct validity of the treatment satisfaction questionnaire for medication (TSQM version II) among outpatient pharmacy consumers. Value in Health, 8(Suppl 1), S9–S24.

    Article  PubMed  Google Scholar 

  25. Aaronson, N., Alonso, J., Burnam, A., Lohr, K. N., Patrick, D. L., Perrin, E., et al. (2002). Scientific advisory committee of the medical outcomes trust: Assessing health status and quality-of-life instruments: Attributes and review criteria. Quality of Life Research, 11(3), 193–205.

    Article  PubMed  Google Scholar 

  26. Wright, B., & Masters, G. (1982). Rating scale analysis: Rasch measurement. Chicago, IL: MESA Press.

    Google Scholar 

  27. Wright, B., & Linacre, J. (1994). Reasonable mean-square fit values. Rasch Measurement Transactions, 8, 370.

    Google Scholar 

  28. Cronbach, L. (1951). Coefficient alpha and the internal structure of tests. Psychometrika, 16, 297–334.

    Article  Google Scholar 

  29. King, P., Kong, M. F., Parkin, H., Macdonald, I. A., & Tattersall, R. B. (1998). Well-being, cerebral function, and physical fatigue after nocturnal hypoglycemia in IDDM. Diabetes Care, 21(3), 341–345.

    Article  CAS  PubMed  Google Scholar 

  30. Jauch-Chara, K., Hallschmid, M., Gais, S., Schmid, S. M., Oltmanns, K. M., Colmorgen, C., et al. (2007). Hypoglycemia during sleep impairs consolidation of declarative memory in type 1 diabetic and healthy humans. Diabetes Care, 30(8), 2040–2045.

    Article  CAS  PubMed  Google Scholar 

  31. Brod, M., Wolden, M., Christensen, T., & Bushnell, D. M. (2013). Understanding the economic burden of non-severe nocturnal hypoglycemic events: Impact on work productivity, disease management, and resource utilization. Value in Health, 16(8), 1140–1149.

  32. Brod, M., Christensen, T., & Bushnell, D. M. (2012). Impact of nocturnal hypoglycemic events on diabetes management, sleep quality, and next-day function. Journal of Medical Economics, 15(1), 77–86.

    Article  PubMed  Google Scholar 

  33. Fanelli, C. G., Paramore, D. S., Hershey, T., Terkamp, C., Ovalle, F., Craft, S., et al. (1998). Impact of nocturnal hypoglycemia on hypoglycemic cognitive dysfunction in type 1 diabetes. Diabetes, 47(12), 1920–1927.

    Article  CAS  PubMed  Google Scholar 

  34. Matyka, K. A., Wigg, L., Pramming, S., Stores, G., & Dunger, D. B. (1999). Cognitive function and mood after profound nocturnal hypoglycaemia in prepubertal children with conventional insulin treatment for diabetes. Archives of Disease in Childhood, 81(2), 138–142.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Fulcher, G., Singer, J., Castañeda, R., Fraige Filho, F., Maffei, L., Snyman, J., et al. (2014). The psychosocial and financial impact of non-severe hypoglycemic events on people with diabetes: Two international surveys. Journal of Medical Economics, 17(10), 751–761.

    Article  PubMed  Google Scholar 

  36. Geelhoed-Duijvestijn, P. H., Pedersen-Bjergaard, U., Weitgasser, R., Lahtela, J., Jensen, M. M., & Östenson, C. G. (2013). Effects of patient-reported non-severe hypoglycemia on healthcare resource use, work-time loss, and wellbeing in insulin-treated patients with diabetes in seven European countries. Journal of Medical Economics, 16(12), 1453–1461.

    Article  PubMed  Google Scholar 

  37. Brod, M., Pohlman, B., Wolden, M., & Christensen, T. (2013). Non-severe nocturnal hypoglycemic events: Experience and impacts on patient functioning and well-being. Quality of Life Research, 22(5), 997–1004.

    Article  PubMed Central  PubMed  Google Scholar 

  38. Brod, M., Wolden, M., Groleau, D., Bushnell, D.M. (2014). Understanding the economic, daily functioning and diabetes management burden of non-severe nocturnal hypoglycemic events in Canada: differences between type 1 and type 2. Journal of Medical Economics, 17(1), 11–20.

  39. Bushnell, D. M., Martin, M. L., & Parasuraman, B. (2003). Electronic versus paper questionnaires: A further comparison in persons with asthma. Journal of Asthma, 40(7), 751–762. doi:10.1081/jas-120023501.

    Article  CAS  PubMed  Google Scholar 

  40. Gwaltney, C. J., Shields, A. L., & Shiffman, S. (2008). Equivalence of electronic and paper-and-pencil administration of patient-reported outcome measures: A meta-analytic review. Value in Health, 11(2), 322–333. doi:10.1111/j.1524-4733.2007.00231.x.

    Article  PubMed  Google Scholar 

  41. Kleinman, L., Leidy, N. K., Crawley, J., Bonomi, A., & Schoenfeld, P. (2001). A comparative trial of paper-and-pencil versus computer administration of the Quality of Life in Reflux and Dyspepsia (QOLRAD) Questionnaire. Medical Care, 39(2), 181–189. doi:10.2307/3768040.

    Article  CAS  PubMed  Google Scholar 

  42. International Program: Country Rank (2014). http://www.census.gov/population/international/data/countryrank/rank.php. Accessed 10 Feb 2014.

  43. The World Factbook (2014). https://www.cia.gov/library/publications/the-world-factbook/. Accessed 10 Feb 2014.

Download references

Acknowledgments

This study was funded by Novo Nordisk A/S.

Author information

Authors and Affiliations

  1. The Brod Group, 219 Julia Avenue, Mill Valley, CA, 94941, USA

    Meryl Brod

  2. Novo Nordisk A/S, Global Development, Søborg, Denmark

    Lise Højbjerre & Charlotte Thim Hansen

  3. Health Research Associates, Inc., Mountlake Terrace, WA, USA

    Donald M. Bushnell

Authors
  1. Meryl Brod
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lise Højbjerre
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Donald M. Bushnell
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Charlotte Thim Hansen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Meryl Brod.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Brod, M., Højbjerre, L., Bushnell, D.M. et al. Assessing the impact of non-severe hypoglycemic events and treatment in adults: development of the Treatment-Related Impact Measure—Non-severe Hypoglycemic Events (TRIM-HYPO). Qual Life Res 24, 2971–2984 (2015). https://doi.org/10.1007/s11136-015-1023-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11136-015-1023-6

Keywords

Search

Navigation