Impact of individualized pharmaceutical care on efficacy and safety of opioid-tolerant outpatients with cancer pain: a multicenter randomized controlled trial

Haiying Ding, Yu Song, Nan Wu, Xiaowei Zheng, Qing Wei, Yancai Sun, Ruixiang Xie, Qing Zhai, Silu Xu, Yajun Qi, Yinghong Wang, Hui Li, Lin Yang, Qing Fan, Qiuling Zhao, Juan Chen, Jing Shi, Cunxian Duan, Qiong Du, Yiwen Zhang, Zhengbo Song, Shuang Fu, Yunfang Cai, Xianhong Huang, Luo Fang, Yuguo Liu, Ping Huang, Haiying Ding, Yu Song, Nan Wu, Xiaowei Zheng, Qing Wei, Yancai Sun, Ruixiang Xie, Qing Zhai, Silu Xu, Yajun Qi, Yinghong Wang, Hui Li, Lin Yang, Qing Fan, Qiuling Zhao, Juan Chen, Jing Shi, Cunxian Duan, Qiong Du, Yiwen Zhang, Zhengbo Song, Shuang Fu, Yunfang Cai, Xianhong Huang, Luo Fang, Yuguo Liu, Ping Huang

Abstract

Background: Managing cancer pain is a growing challenge. Individualized pharmaceutical care is particularly important for opioid-tolerant outpatients due to variation in terms of their knowledge about pain, treatment adherence, and risk of experiencing inadequate analgesia and severe adverse events. This study aimed to determine the influence of individualized pharmaceutical care on outcomes in opioid-tolerant outpatients with cancer pain.

Methods: A multicenter, open-label, randomized, controlled study was carried out. Opioid-tolerant outpatients experiencing chronic cancer pain and receiving sustained-release opioids were randomly assigned to the intervention group and the control group with a 1:1 ratio. The intervention group received individualized pharmaceutical care, while the control group received conventional care during 4-week period. The primary endpoint was medication adherence on the intention-to-treat (ITT) population. Secondary outcomes included the patients' knowledge of cancer pain and pain medications, pain score, frequency of breakthrough pain, quality of life (QoL) which were assessed on the ITT population. Adverse events were evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) version 4.0 on the per-protocol (PP) population.

Results: A total of 118 patients were enrolled, and 102 patients (51 in each group) completed the 30-day follow-up from six oncology centers in China. The proportion of patients adhering to opioid medication increased to similar levels in the two groups during the 4 weeks (P=0.149). The intervention group had a significantly lower pain score at 4 weeks compared to the control group (P=0.015), and the proportion of participants without breakthrough pain was significantly higher at 4 weeks than at baseline in the intervention group (P=0.029), but not in the control group (P=0.322). The two groups did not differ significantly in terms of QoL or adverse events.

Conclusions: Our results suggest that individualized pharmaceutical care can markedly reduce patient-related problems and significantly improve pain control in opioid-tolerant outpatients. These findings validate the recommendations to include clinical pharmacists in the management of cancer pain.

Trial registration: ClinicalTrials.gov identifier: NCT03439904.

Keywords: Cancer pain; opioids; outpatients; pharmaceutical service; pharmacists.

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-4091/coif). All authors report that this study was sponsored by Mundipharma (China) Pharmaceutical. However, the sponsor did not participate in the conduct of the study and analysis of the data. The authors have no other conflicts of interest to declare.

2022 Annals of Translational Medicine. All rights reserved.

Figures

Figure 1
Figure 1
Scheme of the individualized intervention provided by pharmacists to the intervention group.
Figure 2
Figure 2
Flow diagram of patient enrollment and analysis. ITT, intention-to-treat; PP, per-protocol.
Figure 3
Figure 3
The diverse interventions provided by pharmacists to the intervention group, and the numbers of patients receiving each intervention.

References

    1. Esnaola NF, Cantor SB, Johnson ML, et al. Pain and quality of life after treatment in patients with locally recurrent rectal cancer. J Clin Oncol 2002;20:4361-7. 10.1200/JCO.2002.02.121
    1. Scarborough BM, Smith CB. Optimal pain management for patients with cancer in the modern era. CA Cancer J Clin 2018;68:182-96. 10.3322/caac.21453
    1. Portenoy RK, Lesage P. Management of cancer pain. Lancet 1999;353:1695-700. 10.1016/S0140-6736(99)01310-0
    1. van den Beuken-van Everdingen MH, Hochstenbach LM, Joosten EA, et al. Update on Prevalence of Pain in Patients With Cancer: Systematic Review and Meta-Analysis. J Pain Symptom Manage 2016;51:1070-90.e9. 10.1016/j.jpainsymman.2015.12.340
    1. Atayee RS, Sam AM, Edmonds KP. Patterns of Palliative Care Pharmacist Interventions and Outcomes as Part of Inpatient Palliative Care Consult Service. J Palliat Med 2018;21:1761-7. 10.1089/jpm.2018.0093
    1. Greco MT, Roberto A, Corli O, et al. Quality of cancer pain management: an update of a systematic review of undertreatment of patients with cancer. J Clin Oncol 2014;32:4149-54. 10.1200/JCO.2014.56.0383
    1. Yu S, Wang XS, Cheng Y, et al. Special aspects of cancer pain management in a Chinese general hospital. Eur J Pain 2001;5 Suppl A:15-20.
    1. Deandrea S, Montanari M, Moja L, et al. Prevalence of undertreatment in cancer pain. A review of published literature. Ann Oncol 2008;19:1985-91. 10.1093/annonc/mdn419
    1. Janjan N. Improving cancer pain control with NCCN guideline-based analgesic administration: a patient-centered outcome. J Natl Compr Canc Netw 2014;12:1243-9. 10.6004/jnccn.2014.0122
    1. Zylla D, Kuskowski MA, Gupta K, et al. Association of opioid requirement and cancer pain with survival in advanced non-small cell lung cancer. Br J Anaesth 2014;113:i109-16. 10.1093/bja/aeu351
    1. Halabi S, Lin CY, Kelly WK, et al. Updated prognostic model for predicting overall survival in first-line chemotherapy for patients with metastatic castration-resistant prostate cancer. J Clin Oncol 2014;32:671-7. 10.1200/JCO.2013.52.3696
    1. Quinten C, Coens C, Mauer M, et al. Baseline quality of life as a prognostic indicator of survival: a meta-analysis of individual patient data from EORTC clinical trials. Lancet Oncol 2009;10:865-71. 10.1016/S1470-2045(09)70200-1
    1. Halabi S, Vogelzang NJ, Kornblith AB, et al. Pain predicts overall survival in men with metastatic castration-refractory prostate cancer. J Clin Oncol 2008;26:2544-9. 10.1200/JCO.2007.15.0367
    1. Efficace F, Bottomley A, Smit EF, et al. Is a patient's self-reported health-related quality of life a prognostic factor for survival in non-small-cell lung cancer patients? A multivariate analysis of prognostic factors of EORTC study 08975. Ann Oncol 2006;17:1698-704. 10.1093/annonc/mdl183
    1. Herndon JE, 2nd, Fleishman S, Kornblith AB, et al. Is quality of life predictive of the survival of patients with advanced nonsmall cell lung carcinoma? Cancer 1999;85:333-40. 10.1002/(SICI)1097-0142(19990115)85:2<333::AID-CNCR10>;2-Q
    1. Franco J, de Souza RN, Lima TM, et al. Role of clinical pharmacist in the palliative care of adults and elderly patients with cancer: A scoping review. J Oncol Pharm Pract 2022;28:664-85. 10.1177/10781552211073470
    1. Shrestha S, Kc B, Blebil AQ, et al. Pharmacist Involvement in Cancer Pain Management: A Systematic Review and Meta-Analysis. J Pain 2022;23:1123-42. 10.1016/j.jpain.2022.02.002
    1. Marchese M, Zhu C, Charbonneau LF, et al. Description and Disposition of Patients with Cancer Accessing a Novel, Pharmacist-Led Cannabis Consultation Service. JCO Oncol Pract 2022. [Epub ahead of print]. doi: .10.1200/OP.21.00748
    1. Liu J, Wang C, Chen X, et al. Evaluation of pharmacist interventions as part of a multidisciplinary cancer pain management team in a Chinese academic medical center. J Am Pharm Assoc (2003) 2020;60:76-80. 10.1016/j.japh.2019.09.005
    1. Ding H, Zheng X, Kong S, et al. Multidisciplinary intervention incorporating pharmacists in management of opioid-naïve patients with moderate to severe cancer pain. Eur J Cancer Care (Engl) 2020;29:e13225. 10.1111/ecc.13225
    1. Kwon JH. Overcoming barriers in cancer pain management. J Clin Oncol 2014;32:1727-33. 10.1200/JCO.2013.52.4827
    1. Jacobsen R, Møldrup C, Christrup L, et al. Patient-related barriers to cancer pain management: a systematic exploratory review. Scand J Caring Sci 2009;23:190-208. 10.1111/j.1471-6712.2008.00601.x
    1. Davis MP, Walsh D. Epidemiology of cancer pain and factors influencing poor pain control. Am J Hosp Palliat Care 2004;21:137-42. 10.1177/104990910402100213
    1. Miaskowski C, Dodd MJ, West C, et al. Lack of adherence with the analgesic regimen: a significant barrier to effective cancer pain management. J Clin Oncol 2001;19:4275-9. 10.1200/JCO.2001.19.23.4275
    1. Vieira CMP, Fragoso RM, Pereira D, et al. Pain polymorphisms and opioids: An evidence based review. Mol Med Rep 2019;19:1423-34.
    1. Edwards Z, Ziegler L, Craigs C, et al. Pharmacist educational interventions for cancer pain management: a systematic review and meta-analysis. Int J Pharm Pract 2019;27:336-45. 10.1111/ijpp.12516
    1. Chen J, Lu XY, Wang WJ, et al. Impact of a clinical pharmacist-led guidance team on cancer pain therapy in China: a prospective multicenter cohort study. J Pain Symptom Manage 2014;48:500-9. 10.1016/j.jpainsymman.2013.10.015
    1. Wang Y, Huang H, Zeng Y, et al. Pharmacist-led medication education in cancer pain control: a multicentre randomized controlled study in Guangzhou, China. J Int Med Res 2013;41:1462-72. 10.1177/0300060513491170
    1. Wang Y, Wu H, Xu F. Impact of Clinical Pharmacy Services on KAP and QOL in Cancer Patients: A Single-Center Experience. Biomed Res Int 2015;2015:502431. 10.1155/2015/502431
    1. Yamada M, Matsumura C, Jimaru Y, et al. Effect of Continuous Pharmacist Interventions on Pain Control and Side Effect Management in Outpatients with Cancer Receiving Opioid Treatments. Biol Pharm Bull 2018;41:858-63. 10.1248/bpb.b17-00749
    1. Yennurajalingam S, Edwards T, Arthur JA, et al. Predicting the risk for aberrant opioid use behavior in patients receiving outpatient supportive care consultation at a comprehensive cancer center. Cancer 2018;124:3942-9. 10.1002/cncr.31670
    1. Mearis M, Shega JW, Knoebel RW. Does adherence to National Comprehensive Cancer Network guidelines improve pain-related outcomes? An evaluation of inpatient cancer pain management at an academic medical center. J Pain Symptom Manage 2014;48:451-8. 10.1016/j.jpainsymman.2013.09.016
    1. Macintyre PE, Roberts LJ, Huxtable CA. Management of Opioid-Tolerant Patients with Acute Pain: Approaching the Challenges. Drugs 2020;80:9-21. 10.1007/s40265-019-01236-4
    1. Valeberg BT, Miaskowski C, Hanestad BR, et al. Prevalence rates for and predictors of self-reported adherence of oncology outpatients with analgesic medications. Clin J Pain 2008;24:627-36. 10.1097/AJP.0b013e31816fe020
    1. Fallon M, Giusti R, Aielli F, et al. Management of cancer pain in adult patients: ESMO Clinical Practice Guidelines. Ann Oncol 2018;29:iv166-91. 10.1093/annonc/mdy152
    1. National Health Commission of the People’s Republic of China. WS/T 404.1-2012, Reference intervals for common clinical biochemistry tests—part 1: Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gama-glutamyltransferase. Available online: (Accessed August 1, 2013).
    1. Morisky DE, Green LW, Levine DM. Concurrent and predictive validity of a self-reported measure of medication adherence. Med Care 1986;24:67-74. 10.1097/00005650-198601000-00007
    1. Langley PC, Ruiz-Iban MA, Molina JT, et al. The prevalence, correlates and treatment of pain in Spain. J Med Econ 2011;14:367-80. 10.3111/13696998.2011.583303
    1. Kim HJ, Jung SO. Comparative evaluations of single-item pain-intensity measures in cancer patients: Numeric rating scale vs. verbal rating scale. J Clin Nurs 2020;29:2945-52. 10.1111/jocn.15341
    1. Liu GG, Wu H, Li M, et al. Chinese time trade-off values for EQ-5D health states. Value Health 2014;17:597-604. 10.1016/j.jval.2014.05.007
    1. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Available online: (Accessed September, 29, 2021).
    1. National Health Commission of the People’s Republic of China. A notice on the establishment of good pain management ward from the National Health Commission of China. Available online: (Accessed October 4, 2021).
    1. National Cancer Institute. Pain in People with Cancer. Available online: (Updated: October 9, 2021).
    1. National Cancer Institute. Cancer Pain (PDQ®)–Health Professional Version. Available online: (Updated: October 9, 2021).
    1. Gagnon L, Fairchild A, Pituskin E, et al. Optimizing pain relief in a specialized outpatient palliative radiotherapy clinic: contributions of a clinical pharmacist. J Oncol Pharm Pract 2012;18:76-83. 10.1177/1078155211402104
    1. van Boven JF, Stuurman-Bieze AG, Hiddink EG, et al. Medication monitoring and optimization: a targeted pharmacist program for effective and cost-effective improvement of chronic therapy adherence. J Manag Care Spec Pharm 2014;20:786-92.
    1. Alfian SD, van Boven JFM, Abdulah R, et al. Effectiveness of a targeted and tailored pharmacist-led intervention to improve adherence to antihypertensive drugs among patients with type 2 diabetes in Indonesia: A cluster randomised controlled trial. Br J Clin Pharmacol 2021;87:2032-42. 10.1111/bcp.14610
    1. Li Q, Wan X. Progress of pain assessment and analgesia strategy for mechanical ventilation patients. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2017;29:861-4.
    1. National Health Commission of the People’s Republic of China . Guidelines for diagnosis and treatment of cancer pain. Chinese Clinical Oncology 2018;23:937-44.
    1. NCCN Clinical Practice Guidelines in Oncology. Adult Cancer Pain. Version 1. April 8, 2020. Available online: (Accessed April 8, 2020).

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir