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Evaluation of Minimal Important Difference and Responder Definition in the EORTC QLQ-PAN26 Module for Assessing Health-Related Quality of Life in Patients with Surgically Resected Pancreatic Adenocarcinoma

  • Global Health Services Research
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Although the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-PAN26 is widely used to assess health-related quality of life (HRQoL), its group-level minimal important difference (MID) and individual-level responder definition (RD) are not established; we calculated MID and RD using HRQoL data from the APACT trial in patients with surgically resected pancreatic cancer who received adjuvant chemotherapy.

Methods

HRQoL was assessed using EORTC QLQ-C30 and QLQ-PAN26 at baseline, during treatment, at end of treatment, and during follow-up. Distribution-based MIDs were estimated using 0.5 × baseline standard deviation (SD) and reliability-based (intraclass correlation) standard error of measurement (SEM). Anchor-based MIDs and RDs (anchor, QLQ-C30 overall health) were estimated using a linear mixed model.

Results

Overall, 772 patients completed the baseline assessment. Distribution-based MIDs (0.5 × SD) for QLQ-PAN26 scales ranged from 12 to 13, except hepatic symptoms (≈8), pancreatic pain (≈10), and sexual dysfunction (≈17); those for stand-alone items ranged from 12 to 16. The SEM values were similar. Among scales/items sufficiently correlated (r > 0.30) with the anchor, MIDs ranged from 5 to 9. Within-patient QLQ-PAN26 RD estimates varied by direction (deterioration vs. improvement) and scale/item, but all values were lower than the true possible within-patient change (e.g. 16.7 points for a two-item scale) given a one-category change on the raw scale.

Conclusions

Compared with distribution-based MIDs, anchor-based MIDs were twice as sensitive in detecting group-level changes in QLQ-PAN26 scales/items. For interpreting clinically meaningful change, RDs cannot be less than the true minimum of the scale. The group-level MID may help clinicians/researchers interpret HRQoL changes.

Trial registration: ClinicalTrials.gov NCT01964430; Eudra CT 2013-003398-91.

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Acknowledgment

This study was funded by Bristol-Myers Squibb Company. The authors thank Olivia (Schmid) Zollinger of Swiss Healthcare Startups for her intellectual contribution to this work. Writing assistance was provided by Narender Dhingra, MBBS, PhD, of MediTech Media, Ltd, and funded by Bristol-Myers Squibb Company. The authors are fully responsible for all content and editorial decisions for this manuscript.

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Authors and Affiliations

  1. Department of Medical Oncology, IRCCS Ospedale San Raffaele Scientific Institute, Milan, Italy

    Michele Reni MD

  2. Bristol Myers Squibb, Princeton, NJ, USA

    Julia Braverman PhD, MS & Brian Lu MD, PhD

  3. Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Andrew Hendifar MD

  4. Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

    Chung-Pin Li MD

  5. National Yang-Ming University School of Medicine, Taipei, Taiwan

    Chung-Pin Li MD

  6. Vall d’Hebrón University Hospital and Vall d’Hebrón Institute of Oncology, IOB Quirón Barcelona, Barcelona, Spain

    Teresa Macarulla MD

  7. Division of Medical Oncology, Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea

    Do-Youn Oh MD

  8. Division of Oncology and Hematology, Charité – Universitätsmedizin, Berlin, Germany

    Hanno Riess MD

  9. Division of Hematology and Oncology, University of California, San Francisco School of Medicine, San Francisco, CA, USA

    Margaret Tempero MD

  10. Pharmerit – an OPEN Health Company, Bethesda, MD, USA

    James Marcus PhD, MA, MS, Namita Joshi PhD, MS & Marc Botteman MA, MS

  11. Mayo Clinic, Scottsdale, AZ, USA

    Amylou C. Dueck PhD

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  1. Michele Reni MD
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  2. Julia Braverman PhD, MS
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Corresponding author

Correspondence to Michele Reni MD.

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Disclosure

MR reports grants, personal fees, and nonfinancial support from Celgene (a Bristol-Myers Squibb Company), Baxalta, Shire, Eli Lilly and Company, Pfizer, Novocure, Novartis, AstraZeneca, Sanofi, Baxter, Servier, and Boston Pharmaceuticals; JB reports employment with Bristol-Myers Squibb Company; AH reports consulting work for Ipsen, Merck, AbbVie, Applied Advanced Therapeutics, and Novartis; CPL and ACD have nothing to disclose; TM reports honoraria for consultancy with Advance Medical HCMS, Baxter, BioLineRX Ltd, Celgene SLU, Eisai, Genzyme, Incyte, IPSEN Pharma Lab, Menarini Lab, Servier, Lilly, Merck Sharp and Dohme, Prime Oncology EU, QED Therapeutics Inc, Sanofi-Aventis and declares institutional financial interests (paid directly to his institution) with Agios, Aslan, AstraZeneca, Bayer, Celgene (a Bristol-Myers Squibb Company), Genentech, Hallozyme, Immunomedics, Lilly, Merrimack, Millennium, Novartis, Pfizer, Pharmacyclics, and Roche; DYO reports consulting/advisory role with AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho Pharmaceutical, and Aslan Pharmaceuticals; research funding from AstraZeneca, Novartis, Array BioPharma, Eli Lilly and Company, and GC Pharma; HR reports consulting/advisory role with Bayer, Boehringer Ingelheim, Bristol-Myers Squibb Company, Celgene (a Bristol-Myers Squibb Company), Daiichi Sankyo, Johnson & Johnson, and Pfizer; speakers bureaus from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb Company, Celgene (a Bristol-Myers Squibb Company), Daiichi Sankyo, LEO Pharma, and Pfizer; research funding from Bayer, Celgene (a Bristol-Myers Squibb Company), and LEO Pharma; MT reports consulting with AbbVie, Advance Medical, BioPharm Communications, Bristol-Myers Squibb Company, Celgene (a Bristol-Myers Squibb Company), Eisai, Ignyta, Pharmacyclics, PharmaCyte Biotech, and Tocagen; advisory board with AstraZeneca, Cancer Prevention and Research Institute of Texas, and Immunovia; research contract with Halozyme Therapeutics; BL reports employment and stock ownership with Bristol-Myers Squibb Company; JM reports employment with Pharmerit International, LP; consulting fees from Celgene (a Bristol-Myers Squibb Company); NJ reports employment with Pharmerit – an OPEN Health Company; consulting with Celgene (a Bristol-Myers Squibb Company); MB reports employment and stock ownership with Pharmerit – an OPEN Health Company and grants from Celgene (a Bristol-Myers Squibb Company).

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Bristol Myers Squibb policy on data sharing may be found at https://www.bms.com/researchers-and-partners/independent-research/data-sharing-request-process.html.

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Reni, M., Braverman, J., Hendifar, A. et al. Evaluation of Minimal Important Difference and Responder Definition in the EORTC QLQ-PAN26 Module for Assessing Health-Related Quality of Life in Patients with Surgically Resected Pancreatic Adenocarcinoma. Ann Surg Oncol 28, 7545–7554 (2021). https://doi.org/10.1245/s10434-021-09816-z

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