Patient Preferences for Unresectable Hepatocellular Carcinoma Treatments: A Discrete-Choice Experiment
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Study Population
2.3. Data Analysis
2.3.1. Preference Weights
2.3.2. Conditional Relative Importance
2.3.3. Minimum Overall Survival Required to Offset Changes in Other Treatment Attributes
2.3.4. Simulation
3. Results
3.1. Respondent Characteristics
3.2. Preference Weights and Conditional Relative Importance
3.3. Minimum Overall Survival Required to Offset Changes in Other Treatment Attributes
3.4. Predicted Choice Probabilities
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A. Attribute Descriptions from the Survey
Patient-Friendly Attribute Label | Description in Survey |
---|---|
How long can the medicine extend your life | An important goal of cancer medicines is to increase the length of time during and after the treatment that a patient lives with the cancer. Different medicines work for different amounts of time. We will ask you to think about medicines that can extend your life between 10 months and 20 months. |
Number of months to noticeable decline in ability to do activities | Some cancer medicines can help maintain your ability to perform daily activities without noticeable difficulty while you are taking the medicine. For example, you can continue to do things like take a walk, carry shopping bags, and take care of yourself (eating, dressing, and washing up) without additional difficulty while on treatment. We will ask you to think about medicines that allow you to keep doing your activities with very little difficulty for 3 months to 13 months. After this time, your ability to do these activities will noticeably decline. |
Redness and sores on your hands and feet | Some cancer medicines increase the risk of a rash that causes redness, swelling, blisters, and pain on your hands or feet. We will ask you to think about cancer medicines that may result in different levels of rash that causes redness, swelling, blisters, and pain. There are three possibilities. None:
|
High blood pressure | Some cancer medicines can cause an increase in blood pressure. People who already have high blood pressure may have an increase in their blood pressure. People who do not have high blood pressure may develop it. Generally, there are no symptoms associated with high blood pressure, but high blood pressure can lead to more serious health problems and needs to be monitored and controlled as part of the disease. Untreated high blood pressure increases your risk of serious health problems such as severe headache, heart attack, stroke, or kidney disease. Your doctor will check your blood pressure every month. If your blood pressure increases while taking cancer medicines, your doctor may start you on blood pressure medicines or change your current blood pressure medicines to lower your blood pressure to the normal range. Side effects of blood pressure medicines can include dizziness, drowsiness, headaches, weakness, dry mouth, or other side effects. One in 10 patients will have one of these side effects from the high blood pressure medicines. We will ask you to think about cancer medicines that may result in different levels of high blood pressure. There are three possibilities. None:
|
Risk of bleeding in the digestive tract | Patients with liver cancer can experience bleeding in their digestive tract as a symptom of the cancer. Some medicines may also cause bleeding in the digestive tract during treatment. When patients take a medicine that may cause digestive tract bleeding, the doctor may do tests to check whether the patient is at risk of bleeding. If the doctor decides the patient is not at risk of bleeding, most patients can take the medicine and have no bleeding problems. However, even after testing, some patients who take the medicine will develop bleeding in the digestive tract. People with gastrointestinal (GI) bleeding can experience severe problems like anemia, or even shock, and they may need to be treated at the hospital. Gastrointestinal bleeding can be life-threatening if it is not treated. Your doctor will monitor you for signs of GI bleeding after you start treatment. Later in this survey, we will ask you to think about cancer medicines that have different risks of GI bleeding that range from a 2% risk to a 7% risk. |
How you take the medicine, how often and where | Medicines used to treat cancer can be taken as a pill or by an intravenous (IV) infusion, and they can be taken on different schedules. They can also be taken at home or in a doctor’s office, outpatient clinic, or hospital.
We will ask you to think about medicines that can be taken in different ways and on different schedules. There are four possibilities: Pill once or twice daily at the same time during the day:
|
Appendix B. Preference Weight Analysis
- Treatment that extends life for longer
- Treatment that provides more months in which respondents are able to do activities without decline
- Treatment that causes less-severe palmar-plantar syndrome (although respondents were indifferent to changes in palmar-plantar syndrome from mild to none)
- Treatment that causes less-severe hypertension
- Treatment with less risk of bleeding in the digestive tract (although respondents were indifferent to the risk of bleeding in the digestive tract from treatment decreasing from 5% to 2% and from 7% to 5%)
- Treatment that can be orally administered during the day compared with 30 min to 1 h IV infusion every 3 weeks plus a pill daily (although respondents were indifferent to changes across the other levels in mode and frequency of administration)
Appendix C. Subgroup Analysis
- Self-transportation: respondents who walk or drive themselves to their cancer treatments at least some of the time versus respondents who never walk or drive themselves to their cancer treatments
- Public transportation: respondents who use public or hospital transportation to get to their cancer treatments versus respondents who never use public or hospital transportation to get to their cancer treatments
Subgroup Pair | Subgroup Description | Sample Size (N = 200) | p Value from the Log Likelihood Test of Joint Statistical Significance |
---|---|---|---|
Aged 70 years or older | Younger than 70 years | 172 | 0.491 |
70 years or older | 28 | ||
Race | Does not identify as White a | 126 | 0.733 |
Exclusively White | 42 | ||
Geographic region | Lives in the Midwest, South, or Northeast | 75 | 0.359 |
Lives in the West | 125 | ||
Ability | Is unable to do work activities or needs help taking care of self | 98 | 0.629 |
Is fully active or is able to do activities that are not physically demanding | 102 | ||
Distance to cancer treatment | Travels less than 30 min to cancer treatments | 62 | 0.838 |
Travels 30 min or more to cancer treatments | 137 | ||
Self-transportation | Never walks or drives themselves to cancer treatments | 116 | 0.018 |
Walks or drives themselves to cancer treatments at least some of the time | 84 | ||
Public/hospital transportation | Never uses public or hospital transportation to cancer treatments | 142 | 0.009 |
Uses public or hospital transportation to cancer treatments at least some of the time | 58 | ||
Palmar-plantar syndrome | Has never experienced palmar-plantar syndrome as a side effect of treatment for HCC | 102 | 0.374 |
Has experienced palmar-plantar syndrome as a side effect of treatment for HCC | 82 | ||
Hypertension | Has never been diagnosed with hypertension | 146 | 0.554 |
Has been diagnosed with hypertension | 52 |
References
- Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer statistics, 2022. CA Cancer J. Clin. 2022, 72, 7–33. [Google Scholar] [CrossRef] [PubMed]
- Daher, S.; Massarwa, M.; Benson, A.A.; Khoury, T. Current and future treatment of hepatocellular carcinoma: An updated comprehensive review. J. Clin. Transl. Hepatol. 2018, 6, 69–78. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Draper, A. A concise review of the changing landscape of hepatocellular carcinoma. Am. J. Manag. Care 2020, 26, S211–S219. [Google Scholar] [CrossRef] [PubMed]
- Cheng, A.L.; Qin, S.; Ikeda, M.; Galle, P.R.; Ducreux, M.; Kim, T.Y.; Lim, H.Y.; Kudo, M.; Breder, V.; Merle, P.; et al. Updated efficacy and safety data from IMbrave150: Atezolizumab plus bevacizumab vs. sorafenib for unresectable hepatocellular carcinoma. J. Hepatol. 2022, 76, 862–873. [Google Scholar] [CrossRef] [PubMed]
- National Comprehensive Cancer Network Guidelines: Hepatobiliary Cancers. Version 3.2022. Available online: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1438 (accessed on 24 October 2022).
- Kudo, M.; Finn, R.S.; Qin, S.; Han, K.H.; Ikeda, K.; Piscaglia, F.; Baron, A.; Park, J.W.; Han, G.; Jassem, J.; et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: A randomised phase 3 non-inferiority trial. Lancet 2018, 391, 1163–1173. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Finn, R.S.; Qin, S.; Ikeda, M.; Galle, P.R.; Ducreux, M.; Kim, T.Y.; Kudo, M.; Breder, V.; Merle, P.; Kaseb, A.O.; et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N. Engl. J. Med. 2020, 382, 1894–1905. [Google Scholar] [CrossRef] [PubMed]
- Galle, P.R.; Finn, R.S.; Qin, S.; Ikeda, M.; Zhu, A.X.; Kim, T.Y.; Kudo, M.; Breder, V.; Merle, P.; Kaseb, A.; et al. Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (Imbrave150): An open-label, randomized, phase 3 trial. Lancet Oncol. 2021, 22, 991–1001. [Google Scholar] [CrossRef] [PubMed]
- Su, G.L.; Altayar, O.; O’Shea, R.; Shah, R.; Estfan, B.; Wenzell, C.; Sultan, S.; Falck-Ytter, Y. AGA Clinical Practice Guideline on Systemic Therapy for Hepatocellular Carcinoma. Gastroenterology 2022, 162, 920–934. [Google Scholar] [CrossRef] [PubMed]
- Lo, S.H.; Sharma, R.; Costentin, C.E.; Aggio, D.; Shergill, S.; Colaone, F.; Brennan, V.K.; Straccia, V.A.; Agirrezabal, I.; Lloyd, A.J. Patient preferences for advanced hepatocellular carcinoma treatment: A multicountry stated preference study. Future Oncol. 2021, 17, 4275–4287. [Google Scholar] [CrossRef] [PubMed]
- Soekhai, V.; de Bekker-Grob, E.W.; Ellis, A.R.; Vass, C.M. Discrete choice experiments in health economics: Past, present and future. Pharmacoeconomics 2019, 37, 201–226. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Finn, R.S.; Qin, S.; Ikeda, M.; Galle, P.R.; Ducreux, M.; Kim, T.; Lim, H.Y.; Kudo, M.; Breder, V.V.; Merle, P.; et al. Imbrave150: Updated overall survival data from a global, randomized, open-label phase III study of atezolizumab + bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma. In Proceedings of the Gastrointestinal Cancers Symposium, Virtual, 15–17 January 2021. [Google Scholar]
- Llovet, J.M.; Ricci, S.; Mazzaferro, V.; Hilgard, P.; Gane, E.; Blanc, J.; de Oliveira, A.C.; Santoro, A.; Raoul, J.; Forner, A.; et al. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 2008, 359, 378–390. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kelley, R.K.; Sangro, B.; Harris, W.P.; Ikeda, M.; Okusaka, T.; Kang, Y.; Qin, S.; Tai, W.M.D.; Lim, H.Y.; Yau, T.; et al. Efficacy, tolerability, and biologic activity of a novel regimen of tremelimumab (T) in combination with durvalumab (D) for patients (pts) with advanced hepatocellular carcinoma (aHCC). J. Clin. Oncol. 2020, 38, 4508. [Google Scholar] [CrossRef]
- Finn, R.S.; Ikeda, M.; Zhu, A.X.; Sung, M.W.; Baron, A.D.; Kudo, M.; Okusaka, T.; Kobayashi, M.; Kumada, H.; Kaneko, S.; et al. Phase Ib study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma. J. Clin. Oncol. 2020, 38, 2960–2970. [Google Scholar] [CrossRef] [PubMed]
- Kelley, R.K.; Oliver, J.W.; Hazra, S.; Benzaghou, F.; Yau, T.; Cheng, A.L.; Rimassa, L. Cabozantinib in combination with atezolizumab versus sorafenib in treatment-naive advanced hepatocellular carcinoma: COSMIC-312 phase III study design. Future Oncol. 2020, 16, 1525–1536. [Google Scholar] [CrossRef] [PubMed]
- El-Khoueiry, A.B.; Yau, T.; Kang, Y.K.; Kim, T.Y.; Santoro, A.; Sangro, B.; Melero, I.; Kudo, M.; Hou, M.M.; Matilla, A.; et al. Nivolumab (NIVO) plus ipilimumab (IPI) combination therapy in patients (Pts) with advanced hepatocellular carcinoma (aHCC): Long-term results from CheckMate 040. J. Clin. Oncol. 2021, 39, 269. [Google Scholar] [CrossRef]
- Common Terminology Criteria for Adverse Events (CTCAE). Version 5.0. Available online: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_8.5x11.pdf (accessed on 2 February 2022).
- Johnson, F.R.; Lancsar, E.; Marshall, D.; Kilambi, V.; Mühlbacher, A.; Regier, D.A.; Bresnahan, B.W.; Kanninen, B.; Bridges, J.F. Constructing experimental designs for discrete-choice experiments: Report of the ISPOR Conjoint Analysis Discrete-Choice Experiment Experimental Design Good Research Practices Task Force. Value Health 2013, 16, 3–13. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hauber, A.B.; González, J.M.; Groothuis-Oudshoorn, C.G.; Prior, T.; Marshall, D.A.; Cunningham, C.; IJzerman, M.J.; Bridges, J.F. Statistical methods for the analysis of discrete choice experiments: A report of the ISPOR Conjoint Analysis Experimental Design Task Force. Value Health 2016, 19, 300–315. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, D.; Sedano, S.; Allen, R.; Gong, J.; Cho, M.; Sharma, S. Current Treatment Landscape for Advanced Hepatocellular Carcinoma: Patient Outcomes and the Impact on Quality of Life. Cancers 2019, 11, 841, PMCID:PMC6627588. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vogel, A.; Qin, S.; Kudo, M.; Su, Y.; Hudgens, S.; Yamashita, T.; Yoon, J.H.; Fartoux, L.; Simon, K.; López, C.; et al. Lenvatinib versus sorafenib for first-line treatment of unresectable hepatocellular carcinoma: Patient-reported outcomes from a randomised, open-label, non-inferiority, phase 3 trial. Lancet Gastroenterol. Hepatol. 2021, 6, 649–658. [Google Scholar] [CrossRef] [PubMed]
- Edeline, J.; Yau, T.; Park, J.W.; Kudo, M.; Han, K.H.; Mathurin, P.; Merle, P.; Finn, R.S.; Müller, T.; Taylor, T.; et al. CheckMate 459: Health-related quality of life (HRQoL) in a randomized, multicenter phase III study of nivolumab (NIVO) versus sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC). J. Clin. Oncol. 2020, 38, 483. [Google Scholar] [CrossRef]
Type of Attribute | Patient-Friendly Attribute Label | Possible Attribute Levels |
---|---|---|
Benefit | How long can the medicine extend your life | 20 months 13 months 10 months |
Benefit | Number of months to noticeable decline in ability to do activities | 13 months 9 months 3 months |
Adverse event | Redness and sores on your hands and feet | None Mild Moderate-to-severe |
Adverse event | High blood pressure | None Mild Moderate-to-severe |
Risk of adverse event | Risk of bleeding in the digestive tract | 2 people out of 100 (2%) 5 people out of 100 (5%) 7 people out of 100 (7%) |
Process | How you take the medicine, how often and where | Pill once or twice daily at the same time during the day 1 to 2½ h IV infusion every 3 weeks 1 to 2½ h IV infusion every 4 weeks 30 min to 1 h IV infusion every 3 weeks + a pill daily |
N = 200 | |
---|---|
Age (mean), years (SD) | 58.9 (11.2) |
Male | 111 (55.5%) |
Race or ethnicity, a n (%) | |
Black or African American | 57 (28.5%) |
Hispanic or Latino | 29 (14.5%) |
White | 42 (21.0%) |
A race not listed or prefer not to answer b | 72 (36.0%) |
Education level, n (%) | |
High school degree or equivalent | 43 (21.5%) |
Some college but no degree, trade/technical/vocational school, 2-year college degree, or other | 74 (37.0%) |
4-year college degree or greater | 83 (41.5%) |
Pre-tax household income in 2020, n (%) | |
Less than USD 50,000 | 67 (33.5%) |
USD 50,000 to USD 99,999 | 60 (30.0%) |
USD 100,000 to USD 149,999 | 12 (6.0%) |
USD 150,000 or more | 43 (21.5%) |
Do not know/not sure or prefer not to say | 18 (9.0%) |
Please select the response that you think best describes how you feel currently, n (%) | |
I need some help taking care of myself, and I spend more than half of waking hours in a bed or chair | 46 (23.0%) |
Time since diagnosis, n (%) | |
Less than 1 year ago | 72 (36.0%) |
1 year to fewer than 5 years ago | 114 (57.0%) |
More than 5 years ago | 14 (7.0%) |
Currently receiving treatment for HCC | 171 (85.5%) |
Among those currently receiving treatment for HCC: a | n = 171 |
Medicines via IV | 88 (51.5%) |
Medicines as oral pills | 122 (71.3%) |
All respondents | |
Has your doctor ever diagnosed you with high blood pressure? | |
Yes | 52 (26.0%) |
No | 146 (73.0%) |
Don’t know or not sure | 2 (1.0%) |
Among those who have been diagnosed with high blood pressure: | n = 52 |
Using the following definitions, how would you describe your high blood pressure? | |
Mild c | 31 (59.6%) |
Moderate-to-severe d | 21 (40.4%) |
Don’t know or not sure | 0 (0.0%) |
Among those who are currently receiving or previously received treatment for HCC: | n = 186 |
Have you ever experienced redness and sores on your hands and feet as a side effect of your liver cancer treatment? | |
Yes | 82 (44.1%) |
No | 102 (54.8%) |
Don’t know or not sure | 2 (1.1%) |
Among those who have experienced redness and sores as a side effect of treatment for HCC: | n = 82 |
Using the following definitions, how would you describe the redness and sores on your hands and feet you experienced? | |
Mild e | 48 (58.5%) |
Moderate-to-severe f | 34 (41.5%) |
Don’t know or not sure | 0 (0.0%) |
Attributes | From Level | To Level | MAB (N = 200) | 95% CI | |
---|---|---|---|---|---|
Number of months you are able to do activities without decline | 13 months | 3 months | >10 | N/A | |
13 months | 9 months | 2.31 | 0.56 | 4.06 | |
9 months | 3 months | 4.69 | −2.66 | 12.03 | |
Redness and sores on your hands and feet | None | Moderate-to-severe | >10 | N/A | |
None | Mild | 0.87 | −0.30 | 2.01 | |
Mild | Moderate-to-severe | >10 | N/A | ||
High blood pressure | None | Moderate-to-severe | >10 | N/A | |
None | Mild | 1.77 | 0.40 | 3.14 | |
Mild | Moderate-to-severe | > 10 | N/A | ||
Risk of bleeding in the digestive tract | 2 people out of 100 (2%) | 7 people out of 100 (7%) | 1.60 | 0.04 | 3.17 |
2 people out of 100 (2%) | 5 people out of 100 (5%) | 0.43 | −0.73 | 1.59 | |
5 people out of 100 (5%) | 7 people out of 100 (7%) | 1.17 | −0.06 | 2.40 | |
How you take the medicine, how often and where | Pill once or twice daily at the same time during the day | 30 min to 1 h IV infusion every 3 weeks + a pill daily | 2.21 | 0.57 | 3.85 |
Pill once or twice daily at the same time during the day | 1 to 2½ h IV infusion every 4 weeks | 1.29 | −0.19 | 2.76 | |
Pill once or twice daily at the same time during the day | 1 to 2½ h IV infusion every 3 weeks | 0.89 | −0.55 | 2.34 | |
1 to 2½ h IV infusion every 3 weeks | 30 min to 1 h IV infusion every 3 weeks + a pill daily | 1.32 | −0.13 | 2.76 | |
1 to 2½ h IV infusion every 4 weeks | 1 to 2½ h IV infusion every 3 weeks | 0.39 | −0.93 | 1.72 | |
1 to 2½ h IV infusion every 4 weeks | 30 min to 1 h IV infusion every 3 weeks + a pill daily | 0.92 | −0.44 | 2.28 |
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Li, D.; Tan, R.; Hernandez, S.; Reilly, N.; Bussberg, C.; Mansfield, C. Patient Preferences for Unresectable Hepatocellular Carcinoma Treatments: A Discrete-Choice Experiment. Cancers 2023, 15, 1470. https://doi.org/10.3390/cancers15051470
Li D, Tan R, Hernandez S, Reilly N, Bussberg C, Mansfield C. Patient Preferences for Unresectable Hepatocellular Carcinoma Treatments: A Discrete-Choice Experiment. Cancers. 2023; 15(5):1470. https://doi.org/10.3390/cancers15051470
Chicago/Turabian StyleLi, Daneng, Ruoding Tan, Sairy Hernandez, Norelle Reilly, Cooper Bussberg, and Carol Mansfield. 2023. "Patient Preferences for Unresectable Hepatocellular Carcinoma Treatments: A Discrete-Choice Experiment" Cancers 15, no. 5: 1470. https://doi.org/10.3390/cancers15051470