Bridging the Regulatory-Payer Evidence Gap: A Case Study With Six Minute Walk Distance and Mortality
Author(s)
Noemi Hummel, PhD1, Agnieszka Kopiec, MSc2, Emi Naslazi, MSc3, Ananth Kadambi, MS, PhD4, Claus C. Becker, MBA, MSc, PhD5.
1Certara, Lörrach, Germany, 2Certara, Krakow, Poland, 3Certara, Breda, Netherlands, 4Certara, San Mateo, CA, USA, 5Belmont Health Economics, Belmont, MA, USA.
1Certara, Lörrach, Germany, 2Certara, Krakow, Poland, 3Certara, Breda, Netherlands, 4Certara, San Mateo, CA, USA, 5Belmont Health Economics, Belmont, MA, USA.
OBJECTIVES: Understanding how clinical outcomes such as improved muscle strength or respiratory function translate into morbidity, mortality or hospitalization supports the creation of a compelling value story for a therapy for payers or health technology assessment (HTA) bodies and enables predictive modeling of cost offsets and return on investment for payers.
METHODS: A targeted literature review (TLR) was conducted to identify publications reporting on the relationship between clinical outcomes such as six-minute walk distance (6MWD) and payer-relevant outcomes including mortality and hospitalization. Log-transformed hazard ratios (HRs) reported in the studies were combined using a random-effects meta-analysis. Heterogeneity between studies was assessed by calculating the I2 value. To analyze the impact of age, sex, length of follow-up and type of disease on the overall HR, meta-regressions were conducted. A sensitivity analysis excluded outlier studies identified with Galbraith plots.
RESULTS: Of the 63 records initially identified in the TLR as reporting on the relationship between 6MWD and mortality, 23 records were selected: 20 individual studies and three meta-analyses, resulting in 48 studies included in the analysis. The studies covered three therapeutic areas: chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and advanced cardiovascular disease (CVD). The meta-analysis showed a significant positive association of a 10-meters increase in 6MWD with survival, with an HR (95% confidence interval [CI]) of 0.9601 (0.9529, 0.9674), P<0.01. The sensitivity analysis confirmed this finding (HR: 0.9632 [0.9568, 0.9697), P<0.01. Between-study heterogeneity was high with I2=92%, P<0.01. Meta-regression results showed lower HRs for younger and for male participants.
CONCLUSIONS: Walking ability has a significant impact on mortality that is more pronounced in younger and male persons. This case study may serve as a blueprint methodology to evaluate further links between clinical and payer-relevant outcomes and to bridge gaps between evidence needs for regulatory submissions and reimbursement.
METHODS: A targeted literature review (TLR) was conducted to identify publications reporting on the relationship between clinical outcomes such as six-minute walk distance (6MWD) and payer-relevant outcomes including mortality and hospitalization. Log-transformed hazard ratios (HRs) reported in the studies were combined using a random-effects meta-analysis. Heterogeneity between studies was assessed by calculating the I2 value. To analyze the impact of age, sex, length of follow-up and type of disease on the overall HR, meta-regressions were conducted. A sensitivity analysis excluded outlier studies identified with Galbraith plots.
RESULTS: Of the 63 records initially identified in the TLR as reporting on the relationship between 6MWD and mortality, 23 records were selected: 20 individual studies and three meta-analyses, resulting in 48 studies included in the analysis. The studies covered three therapeutic areas: chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and advanced cardiovascular disease (CVD). The meta-analysis showed a significant positive association of a 10-meters increase in 6MWD with survival, with an HR (95% confidence interval [CI]) of 0.9601 (0.9529, 0.9674), P<0.01. The sensitivity analysis confirmed this finding (HR: 0.9632 [0.9568, 0.9697), P<0.01. Between-study heterogeneity was high with I2=92%, P<0.01. Meta-regression results showed lower HRs for younger and for male participants.
CONCLUSIONS: Walking ability has a significant impact on mortality that is more pronounced in younger and male persons. This case study may serve as a blueprint methodology to evaluate further links between clinical and payer-relevant outcomes and to bridge gaps between evidence needs for regulatory submissions and reimbursement.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO33
Topic
Clinical Outcomes
Topic Subcategory
Relating Intermediate to Long-term Outcomes
Disease
Cardiovascular Disorders (including MI, Stroke, Circulatory), Respiratory-Related Disorders (Allergy, Asthma, Smoking, Other Respiratory)