Jump to comment:

• Re: Cost-effectiveness analysis of cetuximab combined with chemotherapy as a first-line treatment for patients with RAS wild-type metastatic colorectal cancer based on the TAILOR trial
  Ziyan Chen, Ching-Yuan Chang and Vakaramoko Diaby
  Published on: 4 March 2020

• Published on: 4 March 2020

  Re: Cost-effectiveness analysis of cetuximab combined with chemotherapy as a first-line treatment for patients with RAS wild-type metastatic colorectal cancer based on the TAILOR trial

  • Ziyan Chen, PhD student College of Pharmacy, University of Florida, Gainesville, FL
  • Other Contributors:
    • Ching-Yuan Chang, PhD student
    • Vakaramoko Diaby, Assistant professor

  Dear Editor,

  We read the original study by Wang et al1, published in the February 2020 issue of BMJ open, with much interest. In this study, the authors sought to evaluate the costs, quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratio (ICER) of cetuximab plus FOLFOX-4 when compared to FOLFOX-4 alone among Chinese patients with RAS wild-type metastatic colorectal cancer.1 The authors used a Markov model that was structured around 3 health states [i.e., progression-free survival (PFS), progressive disease (PD) and death], with transition probabilities obtained from parametric fitting of PFS and OS curves from the published TAILOR clinical trial.2 Costs were measured in the societal perspective and the medication costs were calculated assuming with the specific height (161cm), weight (62kg) and a body surface area (1.66 m). Health utilities were obtained from existing literature. Based on the ICER of US$ 16,4044 per QALY and a willingness-to-pay threshold of US$ 28,106 per QALY, the authors concluded that cetuximab plus FOLFOX-4 is not a cost-effective treatment in the Chinese health care setting.

  Although this paper contributes to a better understanding of the alignment between the price of cetuximab and its observed efficacy in the Chinese healthcare setting, we feel that further clarifications of the authors’ methodological choices are warranted for transparency and replication purposes. Below are 5 important points for the autho...

  Show More

  Dear Editor,

  We read the original study by Wang et al1, published in the February 2020 issue of BMJ open, with much interest. In this study, the authors sought to evaluate the costs, quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratio (ICER) of cetuximab plus FOLFOX-4 when compared to FOLFOX-4 alone among Chinese patients with RAS wild-type metastatic colorectal cancer.1 The authors used a Markov model that was structured around 3 health states [i.e., progression-free survival (PFS), progressive disease (PD) and death], with transition probabilities obtained from parametric fitting of PFS and OS curves from the published TAILOR clinical trial.2 Costs were measured in the societal perspective and the medication costs were calculated assuming with the specific height (161cm), weight (62kg) and a body surface area (1.66 m). Health utilities were obtained from existing literature. Based on the ICER of US$ 16,4044 per QALY and a willingness-to-pay threshold of US$ 28,106 per QALY, the authors concluded that cetuximab plus FOLFOX-4 is not a cost-effective treatment in the Chinese health care setting.

  Although this paper contributes to a better understanding of the alignment between the price of cetuximab and its observed efficacy in the Chinese healthcare setting, we feel that further clarifications of the authors’ methodological choices are warranted for transparency and replication purposes. Below are 5 important points for the authors to consider.

  1. Societal perspective: the authors took a societal perspective, which includes the social opportunity costs associated with receiving the treatment.3 According to this perspective, it is our understanding that all resources, including productivity losses due to the illness, should be identified and valued. The authors accounted for productivity losses (indirect costs) using a human capital approach, which consists of valuing people's contributions to society based on their salary or wages. For instance, the authors used the average salary of Chinese workers to account for social opportunity costs. We argue that this may be problematic because the human capital approach may bias against the patients who are not working (patients aged 65+), constituting 22.9% of the study population. This should have been acknowledged in the discussion section of the authors’ papers. One alternative to the human capital approach that the authors could have considered as a sensitivity analysis is the friction cost approach.4 This approach posits that the productivity loss accrued by society is a function of the time needed to replace the absentees (sick patients).

  2. Double counting: A germane issue associated with the perspective is double counting indirect cost in the economic evaluation.5 6 Since the economic losses associated with the illness can theoretically be taken into account as part of QALYs estimation, including indirect cost will double count such costs, which might result in underestimating the cost-effectiveness of the intervention. The issue of double-counting costs and to what extent that might have affected the results of their study would be a great discussion point.

  3. Transition probabilities: The authors claim that they applied the Weibull survival function to fit the Kaplan-Meier PFS and OS from the trial. It would be helpful for readers to know whether authors considered other parametric distributions such as exponential, gamma, log-normal besides Weibull.

  4. Competing risk: The authors used a Markov model for their economic evaluation. As previously mentioned, they derived the transition probabilities from fitting parametric distributions to the Kaplan-Meier PFS and OS curves from the TAILOR trial.2 We argue that the method used by the authors did not explicitly account for competing risks. In estimating the transition probabilities from stable to progression, patients who died without progressing would act as competing events. In other words, the hazard of a progression cannot simply be derived from the probability of the PFS, because the ability to accurately capture survival is dependent upon the combination of the hazards of death and progression. We recommend using Dirichlet distributions, multi-state models or partitioned models that can handle these competing more explicitly than the authors presented.

  5. A growing issue gaining significant attention in the literature is the impact of drug wastage on the estimation of incremental cost-effectiveness ratios. Economic evaluations are often conducted under the assumption that every milligram of a drug is effectively used. However, evidence has demonstrated that, in clinical practice, wastage of residual vial contents caused by the mismatch of vial size and individualized dosing based on the body surface area or weight has the potential to significantly affect overall drug expenditure.7 Since cetuximab is a parenteral drug and has the potential of drug wastage, it is necessary to explicitly take into account drug wastage in such economic evaluation. The authors claimed that the medication costs were calculated based on a case-patient. However, they did not provide detailed information on whether drug wastage was accounted for.

  We would like to reiterate our appreciation of the paper by Wang et al.1 We hope our recommendations will help strengthen the value of their work.

  Disclosures: No funding supported the writing of this letter. The authors report no conflicts of interest related to the subject of this letter.

  References
  1. Wang H, Huang L, Gao P, et al. Cost-effectiveness analysis of cetuximab combined with chemotherapy as a first-line treatment for patients with RAS wild-type metastatic colorectal cancer based on the TAILOR trial. BMJ Open 2020;10(2):e030738. doi: 10.1136/bmjopen-2019-030738 [published Online First: 2020/02/14]
  2. Qin S, Li J, Wang L, et al. Efficacy and Tolerability of First-Line Cetuximab Plus Leucovorin, Fluorouracil, and Oxaliplatin (FOLFOX-4) Versus FOLFOX-4 in Patients With RAS Wild-Type Metastatic Colorectal Cancer: The Open-Label, Randomized, Phase III TAILOR Trial. J Clin Oncol 2018;36(30):3031-39. doi: 10.1200/jco.2018.78.3183 [published Online First: 2018/09/11]
  3. Perspective [online].(2016). York; York Health Economics Consortium; 2016 2016 [Available from: https://yhec.co.uk/glossary/perspective/.
  4. Brouwer WB, Koopmanschap MA. The friction-cost method : replacement for nothing and leisure for free? Pharmacoeconomics 2005;23(2):105-11. doi: 10.2165/00019053-200523020-00002 [published Online First: 2005/03/08]
  5. Neumann PJ. Costing and perspective in published cost-effectiveness analysis. Med Care 2009;47(7 Suppl 1):S28-32. doi: 10.1097/MLR.0b013e31819bc09d [published Online First: 2009/06/19]
  6. Jonsson B. Ten arguments for a societal perspective in the economic evaluation of medical innovations. Eur J Health Econ 2009;10(4):357-9. doi: 10.1007/s10198-009-0173-2 [published Online First: 2009/07/21]
  7. Truong J, Cheung MC, Mai H, et al. The impact of cancer drug wastage on economic evaluations. Cancer 2017;123(18):3583-90. doi: 10.1002/cncr.30807 [published Online First: 2017/06/24]

  Show Less

  Conflict of Interest:
  None declared.

  • Back to top