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Impact of a Clinical Pharmacist-Led Guidance Team on Cancer Pain Therapy in China: A Prospective Multicenter Cohort Study
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Original Article
Impact of a Clinical Pharmacist-Led Guidance Team on Cancer Pain Therapy in China: A Prospective Multicenter Cohort Study Jian Chen, PhD, Xiao-yang Lu, MD, Wei-jia Wang, MD, Bin Shen, MD, Yun Ye, MD, Hong Jiang, MD, Qi-sheng Wang, MD, and Bin Cheng, MD Department of Pharmacy (J.C., X.-y.L.), The First Affiliate Hospital, College of Medicine, Zhejiang University; Department of Pharmacy (W.-j.W.), Hangzhou Cancer Hospital, Hangzhou; Department of Pharmacy (B.S.), The First Hospital of Jiaxing, Jiaxing; Department of Pharmacy (Y.Y.), Beilun People’s Hospital, Ningbo; Department of Pharmacy (H.J.), Shangyu People’s Hospital; Department of Pharmacy (Q.-s.W.), People’s Hospital of Xinchang County, Shaoxing; and Department of Pharmacy (B.C.), Zhengjiang Cancer Hospital, Hangzhou, Zhejiang, People’s Republic of China
Abstract Context. Cancer treatment capacity in China is severely limited relative to the enormous size of the population; and many aspects of treatment, such as opioid protocols for pain control, are not standardized. To improve the quality of drug treatment, clinical pharmacists are taking a more active role in patient care. Objectives. This study compared the effectiveness of opioid treatment between cancer patients receiving interventions from Clinical Pharmacist-Led Guidance Teams (CPGTs) and a comparable control group. Methods. This was a prospective, multicenter, double-arm, controlled study conducted in China. Multidisciplinary guidance teams were established and led by clinical pharmacists with expertise in cancer pain therapy. The CPGTs provided pre-therapy consultation and drug education to physicians, monitored prescriptions during treatment, and conducted patient follow-up. The process and outcome parameters of therapy were collected and analyzed with overall statistics and logistic regression. Results. A total of 542 patients were enrolled, 269 in the CPGT intervention group (CPGT group) and 273 controls. Standardization of opioid administration was improved significantly in the CPGT group, including more frequent pain evaluation (P < 0.001), more standardized dosing titration (P < 0.001), and less frequent meperidine prescriptions (P < 0.001). The pain scores in the CPGT group were significantly improved compared with the control group (P < 0.05). The incidences of gastrointestinal adverse events were significantly lower in the CPGT group (constipation: P ¼ 0.041; nausea: P ¼ 0.028; vomiting: P ¼ 0.035), and overall quality of life was improved (P ¼ 0.032). No opioid addiction was encountered in the CPGT group. Risk analysis revealed that patient follow-up by
Address correspondence to: Xiao-yang Lu, Department of Pharmacy, The First Affiliate Hospital, College of Medicine, Zhejiang University, Qingchun Road Ó 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.
#79, Hangzhou, Zhejiang Province, People’s Republic of China 310003. E-mail: [email protected] Accepted for publication: October 30, 2013. 0885-3924/$ - see front matter http://dx.doi.org/10.1016/j.jpainsymman.2013.10.015
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pharmacists and the controlled dosing of opioids were the major factors in improving treatment efficacy. Conclusion. The CPGTs significantly improved standardization, efficiency, and efficacy of cancer pain therapy in China. In a country where clinical pharmacy is still developing, this is a valuable service model that may enhance cancer treatment capacity and efficacy while promoting recognition of the clinical pharmacy profession. J Pain Symptom Manage 2014;-:-e-. Ó 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. Key Words Cancer pain, clinical pharmacist, intervention, China
Introduction Opioids are indispensable analgesics widely used for the treatment of moderate-to-severe cancer pain. The appropriate use of opioids for cancer pain is considered an index of the level of palliative cancer treatment for a country by the World Health Organization (WHO).1e3 China has a high incidence of cancer (2.8 million cases/year), accounting for 22.3% of all new cases worldwide and 25.9% of all cancer deaths (2.9 million/year), and the incidence and mortality continue to increase.4 Moreover, evidences suggests that therapy for cancer pain is insufficient for a country with such an enormous cancer burden. According to the International Narcotics Control Board, the defined daily dose, which represents person-time of drug use, of morphine in the U.S. from 2007 to 2009 was 2060 per million inhabitants per day, compared with only 17 in China. The defined daily dose of oxycodone in the U.S. was 5962 per million inhabitants per day but only two in China.5 In addition to inadequate dosing, nonstandardized implementation of opioid treatment is common in China. Many physicians prescribe opioids casually and many patients with cancer pain are not properly informed of the side effects and risks of opioids, resulting in largely avoidable adverse events and addiction, which greatly reduce efficacy and quality of life (QOL).6e8 There are several reasons for the poor quality of opioid pain management in China. First, China experienced two wars caused by drug abuse (the first and second opium or AngloChinese wars), which resulted in strict controls on opioid administration to curb abuse. Thus, the supply is insufficient for the modern cancer
burden. Some patients and physicians are afraid of the possibility of addiction and so refuse to take or prescribe them. Second, there is an acute shortage of oncologists in China. Erikson et al9 proposed that there will be a shortage of 2550e4080 practitioners in the U.S. (a number able to handle 9.4e15.0 million patient visits), and China is facing the same problem.10 Overburdened medical staff may neglect cancer pain, resulting in the inappropriate use of opioids. Clinical pharmacy is a relatively new medical profession in China, but practitioners are starting to play a larger role in guiding clinical drug therapy.11,12 However, because of the late development of this profession in China, practitioners must become even more involved in medical affairs to prove the value of their services and to gain the recognition and respect of both other medical professionals and patients. The central aim of the study was to assess the value of Clinical Pharmacist-Led Guidance Teams (CPGTs) as a service model for improving drug delivery and for promoting the role of clinical pharmacy in direct patient care. To this end, we conducted a multicenter, prospective study to compare the standardization and efficacy of cancer pain management in patients receiving interventions by a CPGT with control patients.
Methods Establishment of CPGTs and Delineation of Duties We established multidisciplinary CPGTs for cancer pain therapy. Other members of the
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team included professional registered nurses in oncology, oncologists, and administrators in the Department of Medical Affairs. Clinical pharmacists who had at least two years of residency in an oncology department, licensed, and qualified to manage drugs for cancer pain were identified by the Chinese Ministry of Health. These pharmacists were responsible for physician and patient education, drug-use monitoring, and evaluation of drug responses. In addition, clinical pharmacists consulted in complicated cases (but without prescribing rights), and monitored drug efficacy and toxicity. The registered nurses in oncology were responsible for recording the data and for routine nursing care and patient follow-up. The oncologists evaluated the patients, prescribed the initial drug treatment, and adjusted therapy according to the advice given by the clinical pharmacists or nurses. The administrators in the Department of Medical Affairs were responsible for coordinating all departments involved and ensuring cooperation.
Training of Clinical Pharmacists Before initiating the study, the clinical pharmacists involved were trained for two weeks. The curricula were carefully designed and included opioid pharmacotherapeutics, The National Comprehensive Cancer Network Adult Cancer Pain Guidelines (2011 version),13 the Standard of Diagnosis and Treatment of the Ministry of Health in China (2011 version),14 and related clinical practice guidelines for evaluation of pain and adverse events. An examination was conducted after the training. Those passing the examination were allowed to participate in the study as part of a CPGT.
Patient Selection Inpatients were enrolled in the study between July 2011 and May 2012. The inclusion criteria were: age 18 years or older, diagnosed with cancer pain by an oncologist, and able to receive opioid treatment for more than two weeks. Patients previously treated with opioids also were eligible. The exclusion criteria were: pain caused by acute cancerous symptoms or surgery, persistent nausea, vomiting and/or constipation (which could be exacerbated by opioids), and a score of three or four according to Eastern Cooperative Oncology Group (ECOG) criteria.15 All patients were informed
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of the requirement for long-term drug therapy and follow-up and signed the consent form. The study was approved by a third-party independent ethics committee.
Study Design and Intervention This was a prospective, multicenter, doublearmed cohort study (Fig. 1). The experimental group consisted of medical oncology professionals and their enrolled patients, who both received interventions from the CPGT. The control group comprised medical oncology professionals and their patients but received no guidance from the CPGT. Patients were assigned in order of registration by the Hospital Admission Service Center computer. The duration of the intervention was six months, and the outcomes were evaluated when the study was completed. The interventions led by the CPGT were as follows. Pain Consultation. The CPGT performed a comprehensive pain evaluation before drug administration, and collaborated with physicians to select the drug therapy and titrate the dose according to the pain evaluation. In addition, the CPGT advised on when to switch drugs or doses. Monitoring. Team members monitored the use of opioids through the Hospital Information System every week, commented on unreasonable administration, and sent feedback to the related departments and physicians until the patients were discharged from the hospital. Education. Team members were responsible for educating medical professionals and patients during one-to-one meetings before the treatment. Members also prepared and disseminated educational materials related to cancer pain therapy. Patient Follow-Up. Clinical pharmacists conducted face-to-face or telephonic interviews with patients, in collaboration with nurses. Each patient received the assessments for six months, at the frequency of two times per month. Evaluations assessed pain control and guided the patient on how to prevent adverse events or deal with adverse events if any occurred. When necessary, members also sent feedback to physicians to adjust the therapy.
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Fig. 1. Study Design. PS ¼ Performance Status.
Data Collection The study data were collected from inpatient records and follow-up consultation. Two clinical pharmacists abstracted the data and did the evaluation, respectively. Disagreements were resolved by discussion between these two pharmacists. The criteria were the National Comprehensive Cancer Network Adult Cancer Pain Guidelines 2011 version,13 and the Standard of Diagnosis and Treatment of cancer pain 2011 version.14 Metrics included process and outcome parameters. The process parameters included whether 1) there was a comprehensive pain evaluation (causes, nature, location, and scores of the pain) before administering drugs, 2) the drugs were reasonably selected according to the pain evaluation, 3) dosing was titrated for sustained- or controlled-release drugs or when changing the dosage, and 4) the dosing conversion was correctly conducted before changing opioids.
Outcome parameters included 1) the mean value of pain during the study as obtained from regular patient follow-up and determined by numeric or visual rating scales; 2) whether there was nausea, vomiting, constipation, delirium, excessive sedation, addiction, or other adverse events in patients as revealed by follow-up (criteria for adverse events were gastrointestinal symptoms starting within seven days of opioid administration in the absence of chemotherapy for the past seven days and delirium or addiction occurring at least two weeks after the beginning of opioid treatment. Addiction was defined according to the Chinese Classification and Diagnosis of Mental Diseases, third edition16); and 3) QOL evaluated by patient surveys conducted at the end of the intervention (with QOL instruments for cancer patients, with score ranges from zero to 60).17
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A questionnaire prepared by the CPGT evaluated patient experience with clinical pharmacists and included four questions, namely: 1) Are you familiar with clinical pharmacy?, 2) Do you know how the clinical pharmacist contributed to your treatment?, 3) Are you satisfied with the outcome of this treatment?, and 4) If there were any future problems relating to drug treatment, would you seek help from a clinical pharmacist? The answers were scored as yes ¼ 5, maybe ¼ 3, or no ¼ 1. Recognition and satisfaction were determined by the total score.
Statistical Analysis After anonymous patient coding at all the centers, the data were compiled for analysis at the Department of Pharmacy, First Affiliated Hospital of Medicine College, Zhejiang University. Different methods were selected according to the data type. The cohort variables, parameters for standardized treatment, and adverse events are all categorical variables and were compared using the Chi-squared test or Fisher’s exact test when patient numbers were less than five. The pain scale and QOL scores were not normally distributed continuous variables and so were analyzed using the nonparametric Mann-Whitney U test. Odds ratios (OR) and 95% confidence intervals were used as the combining process and outcome parameters of opioid therapy, and analyzed using a logistic regression model. Risk analysis also was conducted by logistic regression. First, univariate analysis was performed to identify candidate risk factors, and then multivariate analysis including significant factors was performed to identify risk factors independently impacting the outcome of opioid therapy. All reported P-values are two sided, with P-value lower than 0.05 as the significance level. All analyses were performed using Stata 12.0 software (StataCorp LP, College Station, TX).
Results Patient Characteristics We enrolled 570 subjects; 15 were excluded because of poor ECOG Performance Status scores (three or four) or discontinuation of medicine in less than two weeks, and 13 were dropped for other reasons (Fig. 1). The final
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enrollment was 542 subjects, of which 269 were included in the CPGT intervention group and 273 in the control group. Baseline characteristics are presented in Table 1 and did not differ significantly between patient groups.
Standardization of Drug Administration Drug administration in the CPGT group was significantly improved (Table 2). Compared with the control group, there was more frequent evaluation of pain severity before opioid administration (97.4% vs. 71.8%, P < 0.001) and standardized dose titration (91.8% vs. 11.4% for sustained-release formulations, P < 0.001; 68.0% vs. 6.2% for dosage increases, P < 0.001), fewer changes in specific opioids without sufficient reason (8.9% vs. 42.9%, P < 0.001), and fewer errors in dose conversion (6.7% vs. 13.9%, P ¼ 0.017). Furthermore, prescriptions were more standardized in the CPGT intervention group. Compared with controls, there were fewer prescriptions for meperidine (2.9% vs. 11.7%, P < 0.001), fewer instances of two opioids used (10.4% vs. 58.9%, P < 0.001), and more oral administration as the initial choice (2.9% vs. 4.4%, P ¼ 0.031). Sustained-release morphine tablets were used more often in the CPGT group (51.0% vs. 21.2%, P ¼ 0.027) but transdermal Table 1 Baseline Characteristics of Enrolled Patients Characteristics Sex Male Female Age, y <44 44e59 >60 ECOG PS score 0 1 2 Pain site Bone Body Intestinal Nerve Patients referred by Medical oncology Radiation oncology Surgical oncology
Test Group
Control Group
n (%)
n (%)
269 126 (46.8) 143 (53.2)
273 141 (51.6) 132 (48.3)
27 (10.0) 69 (25.6) 173 (64.4)
36 (13.2) 65 (23.8) 172 (63.0)
108 (40.1) 141 (52.4) 20 (74.3)
96 (35.2) 163 (59.7) 14 (5.1)
44 128 87 30
32 154 81 15
(16.3) (47.5) (32.3) (11.2)
161 (59.8) 43 (16.0) 65 (24.2)
(11.7) (56.4) (29.6) (5.5)
143 (52.4) 57 (20.9) 73 (26.7)
ECOG PS ¼ Eastern Cooperative Oncology Group Performance Status.
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Table 2 Evaluation of the Standardization of Opioid Administration Parameters
Test Group (N ¼ 269), n (%)
Control Group (N ¼ 273), n (%)
OR (95% CI)
P-value
262 (97.4) 247 (91.8) 183 (68.0)
196 (71.8) 31 (11.4) 17 (6.2)
3.39 (2.78e4.14) 8.12 (6.34e10.78) 9.67 (8.11e11.02)
<0.001 <0.001 <0.001
8 (2.9) 28 (10.4) 8 (2.9)
32 (11.7) 161 (58.9) 12 (4.4)
0.11 (0.08e0.24) 0.09 (0.08e1.24) 0.78 (0.57e1.11)
<0.001 <0.001 0.031
24 (8.9) 18 (6.7)
117 (42.9) 38 (13.9)
0.17 (0.08e0.18) 0.41 (0.31e0.78)
<0.001 0.017
137 (51.0) 108 (40.1) 24 (8.9)
58 (21.2) 143 (52.4) 72 (26.4)
1.78 (1.49e2.12) 0.73 (0.57e0.91) 0.319 (0.21e0.71)
0.027 0.038 0.018
Pain assessment before therapy Dose titration before sustained-release formulation Dose titration before dosage increase Inappropriate prescription Meperidine prescription Combination of two opioids Did not administer orally Inappropriate conversion Change drug without reason Incorrect dose conversion Opioid analgesics Morphine sustained-release formulation Oxycodone sustained-release formulation Fentanyl transdermal patches OR ¼ odds ratio; CI ¼ confidence interval.
fentanyl less often (8.9% vs. 26.4%, P ¼ 0.018). Detailed data are listed in Table 2.
Pain Control The pain scores for the CPGT and control groups are listed in Table 3, including bone pain (3.1 vs. 4.2, P ¼ 0.038), body pain (1.2 vs. 3.6, P ¼ 0.041), visceral pain (1.9 vs. 3.1, P ¼ 0.024), and nerve pain (2.7 vs. 4.8, P ¼ 0.045). Compared with the controls, the CPGT group exhibited better pain control; all the differences in pain scores reached statistical significance. Mean QOL scores were significantly higher in the CPGT group (48.3 vs. 37.6, P ¼ 0.032).
Adverse Events The CPGT intervention group showed significantly reduced rates of constipation (42.1% vs.
51.4%, P ¼ 0.041), nausea (15.1% vs. 22.8%, P ¼ 0.028), and vomiting (15.7% vs. 22.1%, P ¼ 0.035). Among the mental disturbances related to opioids, there were no significant differences in excessive sedation (7.3% vs. 11.2%, P ¼ 0.062) or delirium (7.3% vs. 11.2%, P ¼ 0.088). There was no difference in the incidence of itchy skin (13.4% vs. 12.4%, P ¼ 0.289). There were five cases of addiction in the control group during therapy, which may be related to the use of meperidine, whereas no addiction cases were encountered in the CPGT group. Detailed data are shown in Table 3.
Patient Feedback A total of 531 patients completed the feedback questionnaires, 259 from the CPGT group and 272 from the control group (Table 4). Scores were significantly higher in the CPGT
Table 3 Evaluation of the Efficacy and Tolerability of Opioid Therapy Parameters
Test Group (N ¼ 269)
Pain score, mean SD Bone Body Visceral Nerve QOL score GI reaction, n (%) Constipation Nausea Vomiting Psychological problem, n (%) Delirium Excessive sedation Itchy skin Addiction
Control Group (N ¼ 273)
OR (95% CI)
P-value
3.1 0.9 1.2 1.1 1.9 1.2 2.7 1.9 48.3 11.3
4.2 1.3 3.6 0.8 3.1 1.1 4.8 1.6 37.6 9.4
0.86 0.91 0.72 0.90 1.21
(0.61e1.32) (0.79e1.30) (0.63e0.99) (0.89e1.14) (0.75e1.58)
0.038 0.041 0.024 0.045 0.032
113 (42.1) 41 (15.1) 42 (15.7)
140 (51.4) 62 (22.8) 60 (22.1)
0.73 (0.61e0.93) 0.62 (0.32e0.99) 0.58 (0.41e0.89)
0.041 0.028 0.035
20 11 36 0.0
30 18 34 5.0
0.78 (0.56e0.98) 0.65 (0.47e0.78) 1.05 (0.87e1.26) d
0.088 0.062 0.289 d
(7.3) (4.1) (13.4) (0)
(11.2) (6.7) (12.4) (1.8)
OR ¼ odds ratio; CI ¼ confidence interval; QOL ¼ quality of life; GI ¼ gastrointestinal.
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Table 4 Patient Feedback Results Question Are you familiar with clinical pharmacy? (mean SD) Do you know how the clinical pharmacist contributed to your treatment? (mean SD) Are you satisfied with the outcome of this treatment? (mean SD) Would you seek help from a clinical pharmacist in the future? (mean SD)
intervention group on all four questions: 1) Are you familiar with clinical pharmacy? (4.7 0.2 vs. 2.1 0.6, P < 0.001); 2) Do you know how the clinical pharmacist contributed to your treatment? (4.2 0.5 vs. 1.6 0.4, P ¼ 0.027); 3) Are you satisfied with the outcome of this treatment? (4.7 0.2 vs. 3.2 0.4, P ¼ 0.015); and 4) If there was a problem related to drug treatment, would you seek help from a clinical pharmacist? (3.8 0.2 vs. 2.2 0.4, P ¼ 0.006).
Risk Factor Analysis We selected age, sex, ECOG score, pain score, dose titration, combination of opioids, conversion of dosing, follow-up by pharmacists, use of sustained-release morphine tablets, use of controlled-release oxycodone tablets, and use of transdermal fentanyl as independent variables, and adverse events including constipation, nausea, and vomiting as dependent variables for logistic regression analysis. Univariate analysis demonstrated that age, sex, dose titration, combination of opioids, and the specific opioid were possible factors impacting adverse events, and so were included in the multivariate analysis. As shown in Fig. 2, multivariate analysis demonstrated that dose titration (constipation: OR ¼ 0.64, P ¼ 0.027; nausea: OR ¼ 0.62, P ¼ 0.035), follow-up by the pharmacist (constipation: OR ¼ 0.40, P < 0.001; nausea: OR ¼ 0.65, P < 0.001; vomiting: OR ¼ 0.63, P ¼ 0.014), age older than 60 years (OR ¼ 0.71, P ¼ 0.031), and female gender (nausea: OR ¼ 0.64, P ¼ 0.014; vomiting: OR ¼ 0.74, P ¼ 0.035) were independent factors affecting the adverse effects of opioid therapy.
Discussion We report the results of a multicenter, prospective, cohort study comparing the clinical experience of cancer patients receiving
Test Group (N ¼ 259)
Control Group (N ¼ 272)
P-value
4.7 0.2 4.2 0.5
2.1 0.6 1.6 0.4
<0.001 0.027
4.7 0.2 3.8 0.2
3.2 0.4 2.2 0.4
0.015 0.006
intervention from a CPGT with a control group of cancer patients. Results confirmed that clinical pharmacists significantly improved the standardization and efficacy of cancer pain therapy. Clinical pharmacy began in China in the 1980s. In the past 10 years, the Ministry of Health established a system for the training and licensing of clinical pharmacists,18 and this has greatly increased the number of practitioners. There are now more than 20,000 clinical pharmacists in China and the numbers are growing every year.19 Moreover, the roles of clinical pharmacists are expanding. Most large treatment hospitals have practitioners providing guidance for clinical drug administration, pharmacology education, and monitoring of drug use. Pain control is a critical aspect of cancer therapy. Medical institutions around the world are improving cancer pain management by including clinical pharmacists on the treatment team. In Canada, clinical pharmacists actively participate in drug therapy for cancer pain and have contributed enormously to improved outcomes.20 In the U.S., some clinical pharmacists monitor patients after release from the hospital and pain scores have improved significantly.21 In these countries, the clinical pharmacist system is rather mature, and opioids are both frequently used and subject to national guidelines. However, cancer pain management is inconsistent in China. In this study, we established multidisciplinary CPGTs in several Chinese provinces to guide and manage therapy for cancer pain. The clinical pharmacist standardized drug administration through physician education, regular treatment monitoring, and consultation. In addition to routine work, clinical pharmacists also expanded their services. In collaboration with CPGT nurses, the clinical pharmacist conducted regular patient follow-ups to assure correct dosing for efficacy and safety. Each
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Fig. 2. Logistic regression analysis for the risk of opioid-induced a) constipation, b) nausea, and c) vomiting in 542 patients who received opioid analgesics for cancer pain. OR ¼ odds ratio; CI ¼ confidence interval.
team also had administrators to ensure cooperation of the staff and support the normal workflow. Most pharmacist recommendations were accepted directly or after discussion with physicians. The most significant improvements in standardization were 1) more comprehensive pain evaluation, 2) better use of sustained-release tablets and dose titration, 3) a significant decrease in meperidine prescriptions, 4) a significant reduction in polytherapy with two opioids, and 5) more accurate drug conversion. Under the guidance of clinical pharmacists and administrative sanction, physicians recognized the importance of standardized opioid administration and made fewer unnecessary dose increases or complete changes in the opioid therapy.
Because of the enhanced standardization, many patient outcomes were improved. The CPGT group showed significantly better pain control and a reduced rate of adverse events (P < 0.05). No patient in the intervention group became addicted, and we believe that this was related to the reduction in the use of meperidine (Table 3). Logistic regression analysis demonstrated a reduced incidence of nausea, vomiting, and constipation in the CPGT group. However, other side effects such as delirium and skin itch did not improve significantly, but these side effects have proven difficult to prevent in general. Both improvement in pain control and reduction in adverse events likely contributed to the improved patient QOL and better understanding of clinical pharmacists in the CPGT group (Table 3).
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Furthermore, we performed a logistic regression analysis to determine the risks of constipation, nausea, and vomiting (the most common side effects and those most impacting QOL; Fig. 2). The results showed that follow up by the clinical pharmacist were the most significant factor reducing adverse events, followed by dose titration. Female patients and those aged older than 60 years benefited most from monitoring by clinical pharmacists. This analysis underscored the importance of opioid dose monitoring by the clinical pharmacist during follow-up. This study has several limitations. First, patients enrolled could not be randomly assigned. Although baseline data were similar between the intervention and control groups, lack of randomization could still lead to differences in unmeasured confounders, which may partially bias results. Second, abstracting data from the charts and interviewing patients were not blinded as to intervention group, which could lead to some bias in the outcome assessment. Third, some data were only obtained by telephone, which might lead to errors in communication. Thus, we recommend community clinical pharmacists should join these CPGTs and collaborate with hospital-based clinical pharmacists to ensure patient monitoring and education.
Conclusion Despite these limitations, this study confirmed that a multidisciplinary CPGT significantly improved the standardization and efficacy of cancer pain therapy. Thus, the hospital CPGT is a promising treatment model that should be replicated in as many centers as possible.
Disclosures and Acknowledgments This research was supported by the National Nature Science Foundation of China (No. 81301892). The authors sincerely thank the First Affiliated Hospital, College of Medicine, Zhejiang University; Hangzhou Cancer Hospital; The First Hospital of Jiaxing; Beilun People’s Hospital; Shangyu People’s Hospital; People’s Hospital of Xinchang County; Zhengjiang Cancer Hospital; Zhejiang Provincial People’s
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Hospital; Wenzhou Central Hospital; The People’s Hospital of Lishui City; Shenzhou People’s Hospital; Sun Yat-Sen University Cancer Center; Ningbo Eye Hospital;The Second People’s Hospital of Xihu District, Hangzhou; and Taizhou Central Hospital for their participation, support, and guidance during this study.
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Journal of Pain and Symptom Management 1
Original Article
Impact of a Clinical Pharmacist-Led Guidance Team on Cancer Pain Therapy in China: A Prospective Multicenter Cohort Study Jian Chen, PhD, Xiao-yang Lu, MD, Wei-jia Wang, MD, Bin Shen, MD, Yun Ye, MD, Hong Jiang, MD, Qi-sheng Wang, MD, and Bin Cheng, MD Department of Pharmacy (J.C., X.-y.L.), The First Affiliate Hospital, College of Medicine, Zhejiang University; Department of Pharmacy (W.-j.W.), Hangzhou Cancer Hospital, Hangzhou; Department of Pharmacy (B.S.), The First Hospital of Jiaxing, Jiaxing; Department of Pharmacy (Y.Y.), Beilun People’s Hospital, Ningbo; Department of Pharmacy (H.J.), Shangyu People’s Hospital; Department of Pharmacy (Q.-s.W.), People’s Hospital of Xinchang County, Shaoxing; and Department of Pharmacy (B.C.), Zhengjiang Cancer Hospital, Hangzhou, Zhejiang, People’s Republic of China
Abstract Context. Cancer treatment capacity in China is severely limited relative to the enormous size of the population; and many aspects of treatment, such as opioid protocols for pain control, are not standardized. To improve the quality of drug treatment, clinical pharmacists are taking a more active role in patient care. Objectives. This study compared the effectiveness of opioid treatment between cancer patients receiving interventions from Clinical Pharmacist-Led Guidance Teams (CPGTs) and a comparable control group. Methods. This was a prospective, multicenter, double-arm, controlled study conducted in China. Multidisciplinary guidance teams were established and led by clinical pharmacists with expertise in cancer pain therapy. The CPGTs provided pre-therapy consultation and drug education to physicians, monitored prescriptions during treatment, and conducted patient follow-up. The process and outcome parameters of therapy were collected and analyzed with overall statistics and logistic regression. Results. A total of 542 patients were enrolled, 269 in the CPGT intervention group (CPGT group) and 273 controls. Standardization of opioid administration was improved significantly in the CPGT group, including more frequent pain evaluation (P < 0.001), more standardized dosing titration (P < 0.001), and less frequent meperidine prescriptions (P < 0.001). The pain scores in the CPGT group were significantly improved compared with the control group (P < 0.05). The incidences of gastrointestinal adverse events were significantly lower in the CPGT group (constipation: P ¼ 0.041; nausea: P ¼ 0.028; vomiting: P ¼ 0.035), and overall quality of life was improved (P ¼ 0.032). No opioid addiction was encountered in the CPGT group. Risk analysis revealed that patient follow-up by
Address correspondence to: Xiao-yang Lu, Department of Pharmacy, The First Affiliate Hospital, College of Medicine, Zhejiang University, Qingchun Road Ó 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.
#79, Hangzhou, Zhejiang Province, People’s Republic of China 310003. E-mail: [email protected] Accepted for publication: October 30, 2013. 0885-3924/$ - see front matter http://dx.doi.org/10.1016/j.jpainsymman.2013.10.015
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pharmacists and the controlled dosing of opioids were the major factors in improving treatment efficacy. Conclusion. The CPGTs significantly improved standardization, efficiency, and efficacy of cancer pain therapy in China. In a country where clinical pharmacy is still developing, this is a valuable service model that may enhance cancer treatment capacity and efficacy while promoting recognition of the clinical pharmacy profession. J Pain Symptom Manage 2014;-:-e-. Ó 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. Key Words Cancer pain, clinical pharmacist, intervention, China
Introduction Opioids are indispensable analgesics widely used for the treatment of moderate-to-severe cancer pain. The appropriate use of opioids for cancer pain is considered an index of the level of palliative cancer treatment for a country by the World Health Organization (WHO).1e3 China has a high incidence of cancer (2.8 million cases/year), accounting for 22.3% of all new cases worldwide and 25.9% of all cancer deaths (2.9 million/year), and the incidence and mortality continue to increase.4 Moreover, evidences suggests that therapy for cancer pain is insufficient for a country with such an enormous cancer burden. According to the International Narcotics Control Board, the defined daily dose, which represents person-time of drug use, of morphine in the U.S. from 2007 to 2009 was 2060 per million inhabitants per day, compared with only 17 in China. The defined daily dose of oxycodone in the U.S. was 5962 per million inhabitants per day but only two in China.5 In addition to inadequate dosing, nonstandardized implementation of opioid treatment is common in China. Many physicians prescribe opioids casually and many patients with cancer pain are not properly informed of the side effects and risks of opioids, resulting in largely avoidable adverse events and addiction, which greatly reduce efficacy and quality of life (QOL).6e8 There are several reasons for the poor quality of opioid pain management in China. First, China experienced two wars caused by drug abuse (the first and second opium or AngloChinese wars), which resulted in strict controls on opioid administration to curb abuse. Thus, the supply is insufficient for the modern cancer
burden. Some patients and physicians are afraid of the possibility of addiction and so refuse to take or prescribe them. Second, there is an acute shortage of oncologists in China. Erikson et al9 proposed that there will be a shortage of 2550e4080 practitioners in the U.S. (a number able to handle 9.4e15.0 million patient visits), and China is facing the same problem.10 Overburdened medical staff may neglect cancer pain, resulting in the inappropriate use of opioids. Clinical pharmacy is a relatively new medical profession in China, but practitioners are starting to play a larger role in guiding clinical drug therapy.11,12 However, because of the late development of this profession in China, practitioners must become even more involved in medical affairs to prove the value of their services and to gain the recognition and respect of both other medical professionals and patients. The central aim of the study was to assess the value of Clinical Pharmacist-Led Guidance Teams (CPGTs) as a service model for improving drug delivery and for promoting the role of clinical pharmacy in direct patient care. To this end, we conducted a multicenter, prospective study to compare the standardization and efficacy of cancer pain management in patients receiving interventions by a CPGT with control patients.
Methods Establishment of CPGTs and Delineation of Duties We established multidisciplinary CPGTs for cancer pain therapy. Other members of the
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team included professional registered nurses in oncology, oncologists, and administrators in the Department of Medical Affairs. Clinical pharmacists who had at least two years of residency in an oncology department, licensed, and qualified to manage drugs for cancer pain were identified by the Chinese Ministry of Health. These pharmacists were responsible for physician and patient education, drug-use monitoring, and evaluation of drug responses. In addition, clinical pharmacists consulted in complicated cases (but without prescribing rights), and monitored drug efficacy and toxicity. The registered nurses in oncology were responsible for recording the data and for routine nursing care and patient follow-up. The oncologists evaluated the patients, prescribed the initial drug treatment, and adjusted therapy according to the advice given by the clinical pharmacists or nurses. The administrators in the Department of Medical Affairs were responsible for coordinating all departments involved and ensuring cooperation.
Training of Clinical Pharmacists Before initiating the study, the clinical pharmacists involved were trained for two weeks. The curricula were carefully designed and included opioid pharmacotherapeutics, The National Comprehensive Cancer Network Adult Cancer Pain Guidelines (2011 version),13 the Standard of Diagnosis and Treatment of the Ministry of Health in China (2011 version),14 and related clinical practice guidelines for evaluation of pain and adverse events. An examination was conducted after the training. Those passing the examination were allowed to participate in the study as part of a CPGT.
Patient Selection Inpatients were enrolled in the study between July 2011 and May 2012. The inclusion criteria were: age 18 years or older, diagnosed with cancer pain by an oncologist, and able to receive opioid treatment for more than two weeks. Patients previously treated with opioids also were eligible. The exclusion criteria were: pain caused by acute cancerous symptoms or surgery, persistent nausea, vomiting and/or constipation (which could be exacerbated by opioids), and a score of three or four according to Eastern Cooperative Oncology Group (ECOG) criteria.15 All patients were informed
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of the requirement for long-term drug therapy and follow-up and signed the consent form. The study was approved by a third-party independent ethics committee.
Study Design and Intervention This was a prospective, multicenter, doublearmed cohort study (Fig. 1). The experimental group consisted of medical oncology professionals and their enrolled patients, who both received interventions from the CPGT. The control group comprised medical oncology professionals and their patients but received no guidance from the CPGT. Patients were assigned in order of registration by the Hospital Admission Service Center computer. The duration of the intervention was six months, and the outcomes were evaluated when the study was completed. The interventions led by the CPGT were as follows. Pain Consultation. The CPGT performed a comprehensive pain evaluation before drug administration, and collaborated with physicians to select the drug therapy and titrate the dose according to the pain evaluation. In addition, the CPGT advised on when to switch drugs or doses. Monitoring. Team members monitored the use of opioids through the Hospital Information System every week, commented on unreasonable administration, and sent feedback to the related departments and physicians until the patients were discharged from the hospital. Education. Team members were responsible for educating medical professionals and patients during one-to-one meetings before the treatment. Members also prepared and disseminated educational materials related to cancer pain therapy. Patient Follow-Up. Clinical pharmacists conducted face-to-face or telephonic interviews with patients, in collaboration with nurses. Each patient received the assessments for six months, at the frequency of two times per month. Evaluations assessed pain control and guided the patient on how to prevent adverse events or deal with adverse events if any occurred. When necessary, members also sent feedback to physicians to adjust the therapy.
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Fig. 1. Study Design. PS ¼ Performance Status.
Data Collection The study data were collected from inpatient records and follow-up consultation. Two clinical pharmacists abstracted the data and did the evaluation, respectively. Disagreements were resolved by discussion between these two pharmacists. The criteria were the National Comprehensive Cancer Network Adult Cancer Pain Guidelines 2011 version,13 and the Standard of Diagnosis and Treatment of cancer pain 2011 version.14 Metrics included process and outcome parameters. The process parameters included whether 1) there was a comprehensive pain evaluation (causes, nature, location, and scores of the pain) before administering drugs, 2) the drugs were reasonably selected according to the pain evaluation, 3) dosing was titrated for sustained- or controlled-release drugs or when changing the dosage, and 4) the dosing conversion was correctly conducted before changing opioids.
Outcome parameters included 1) the mean value of pain during the study as obtained from regular patient follow-up and determined by numeric or visual rating scales; 2) whether there was nausea, vomiting, constipation, delirium, excessive sedation, addiction, or other adverse events in patients as revealed by follow-up (criteria for adverse events were gastrointestinal symptoms starting within seven days of opioid administration in the absence of chemotherapy for the past seven days and delirium or addiction occurring at least two weeks after the beginning of opioid treatment. Addiction was defined according to the Chinese Classification and Diagnosis of Mental Diseases, third edition16); and 3) QOL evaluated by patient surveys conducted at the end of the intervention (with QOL instruments for cancer patients, with score ranges from zero to 60).17
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A questionnaire prepared by the CPGT evaluated patient experience with clinical pharmacists and included four questions, namely: 1) Are you familiar with clinical pharmacy?, 2) Do you know how the clinical pharmacist contributed to your treatment?, 3) Are you satisfied with the outcome of this treatment?, and 4) If there were any future problems relating to drug treatment, would you seek help from a clinical pharmacist? The answers were scored as yes ¼ 5, maybe ¼ 3, or no ¼ 1. Recognition and satisfaction were determined by the total score.
Statistical Analysis After anonymous patient coding at all the centers, the data were compiled for analysis at the Department of Pharmacy, First Affiliated Hospital of Medicine College, Zhejiang University. Different methods were selected according to the data type. The cohort variables, parameters for standardized treatment, and adverse events are all categorical variables and were compared using the Chi-squared test or Fisher’s exact test when patient numbers were less than five. The pain scale and QOL scores were not normally distributed continuous variables and so were analyzed using the nonparametric Mann-Whitney U test. Odds ratios (OR) and 95% confidence intervals were used as the combining process and outcome parameters of opioid therapy, and analyzed using a logistic regression model. Risk analysis also was conducted by logistic regression. First, univariate analysis was performed to identify candidate risk factors, and then multivariate analysis including significant factors was performed to identify risk factors independently impacting the outcome of opioid therapy. All reported P-values are two sided, with P-value lower than 0.05 as the significance level. All analyses were performed using Stata 12.0 software (StataCorp LP, College Station, TX).
Results Patient Characteristics We enrolled 570 subjects; 15 were excluded because of poor ECOG Performance Status scores (three or four) or discontinuation of medicine in less than two weeks, and 13 were dropped for other reasons (Fig. 1). The final
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enrollment was 542 subjects, of which 269 were included in the CPGT intervention group and 273 in the control group. Baseline characteristics are presented in Table 1 and did not differ significantly between patient groups.
Standardization of Drug Administration Drug administration in the CPGT group was significantly improved (Table 2). Compared with the control group, there was more frequent evaluation of pain severity before opioid administration (97.4% vs. 71.8%, P < 0.001) and standardized dose titration (91.8% vs. 11.4% for sustained-release formulations, P < 0.001; 68.0% vs. 6.2% for dosage increases, P < 0.001), fewer changes in specific opioids without sufficient reason (8.9% vs. 42.9%, P < 0.001), and fewer errors in dose conversion (6.7% vs. 13.9%, P ¼ 0.017). Furthermore, prescriptions were more standardized in the CPGT intervention group. Compared with controls, there were fewer prescriptions for meperidine (2.9% vs. 11.7%, P < 0.001), fewer instances of two opioids used (10.4% vs. 58.9%, P < 0.001), and more oral administration as the initial choice (2.9% vs. 4.4%, P ¼ 0.031). Sustained-release morphine tablets were used more often in the CPGT group (51.0% vs. 21.2%, P ¼ 0.027) but transdermal Table 1 Baseline Characteristics of Enrolled Patients Characteristics Sex Male Female Age, y <44 44e59 >60 ECOG PS score 0 1 2 Pain site Bone Body Intestinal Nerve Patients referred by Medical oncology Radiation oncology Surgical oncology
Test Group
Control Group
n (%)
n (%)
269 126 (46.8) 143 (53.2)
273 141 (51.6) 132 (48.3)
27 (10.0) 69 (25.6) 173 (64.4)
36 (13.2) 65 (23.8) 172 (63.0)
108 (40.1) 141 (52.4) 20 (74.3)
96 (35.2) 163 (59.7) 14 (5.1)
44 128 87 30
32 154 81 15
(16.3) (47.5) (32.3) (11.2)
161 (59.8) 43 (16.0) 65 (24.2)
(11.7) (56.4) (29.6) (5.5)
143 (52.4) 57 (20.9) 73 (26.7)
ECOG PS ¼ Eastern Cooperative Oncology Group Performance Status.
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Table 2 Evaluation of the Standardization of Opioid Administration Parameters
Test Group (N ¼ 269), n (%)
Control Group (N ¼ 273), n (%)
OR (95% CI)
P-value
262 (97.4) 247 (91.8) 183 (68.0)
196 (71.8) 31 (11.4) 17 (6.2)
3.39 (2.78e4.14) 8.12 (6.34e10.78) 9.67 (8.11e11.02)
<0.001 <0.001 <0.001
8 (2.9) 28 (10.4) 8 (2.9)
32 (11.7) 161 (58.9) 12 (4.4)
0.11 (0.08e0.24) 0.09 (0.08e1.24) 0.78 (0.57e1.11)
<0.001 <0.001 0.031
24 (8.9) 18 (6.7)
117 (42.9) 38 (13.9)
0.17 (0.08e0.18) 0.41 (0.31e0.78)
<0.001 0.017
137 (51.0) 108 (40.1) 24 (8.9)
58 (21.2) 143 (52.4) 72 (26.4)
1.78 (1.49e2.12) 0.73 (0.57e0.91) 0.319 (0.21e0.71)
0.027 0.038 0.018
Pain assessment before therapy Dose titration before sustained-release formulation Dose titration before dosage increase Inappropriate prescription Meperidine prescription Combination of two opioids Did not administer orally Inappropriate conversion Change drug without reason Incorrect dose conversion Opioid analgesics Morphine sustained-release formulation Oxycodone sustained-release formulation Fentanyl transdermal patches OR ¼ odds ratio; CI ¼ confidence interval.
fentanyl less often (8.9% vs. 26.4%, P ¼ 0.018). Detailed data are listed in Table 2.
Pain Control The pain scores for the CPGT and control groups are listed in Table 3, including bone pain (3.1 vs. 4.2, P ¼ 0.038), body pain (1.2 vs. 3.6, P ¼ 0.041), visceral pain (1.9 vs. 3.1, P ¼ 0.024), and nerve pain (2.7 vs. 4.8, P ¼ 0.045). Compared with the controls, the CPGT group exhibited better pain control; all the differences in pain scores reached statistical significance. Mean QOL scores were significantly higher in the CPGT group (48.3 vs. 37.6, P ¼ 0.032).
Adverse Events The CPGT intervention group showed significantly reduced rates of constipation (42.1% vs.
51.4%, P ¼ 0.041), nausea (15.1% vs. 22.8%, P ¼ 0.028), and vomiting (15.7% vs. 22.1%, P ¼ 0.035). Among the mental disturbances related to opioids, there were no significant differences in excessive sedation (7.3% vs. 11.2%, P ¼ 0.062) or delirium (7.3% vs. 11.2%, P ¼ 0.088). There was no difference in the incidence of itchy skin (13.4% vs. 12.4%, P ¼ 0.289). There were five cases of addiction in the control group during therapy, which may be related to the use of meperidine, whereas no addiction cases were encountered in the CPGT group. Detailed data are shown in Table 3.
Patient Feedback A total of 531 patients completed the feedback questionnaires, 259 from the CPGT group and 272 from the control group (Table 4). Scores were significantly higher in the CPGT
Table 3 Evaluation of the Efficacy and Tolerability of Opioid Therapy Parameters
Test Group (N ¼ 269)
Pain score, mean SD Bone Body Visceral Nerve QOL score GI reaction, n (%) Constipation Nausea Vomiting Psychological problem, n (%) Delirium Excessive sedation Itchy skin Addiction
Control Group (N ¼ 273)
OR (95% CI)
P-value
3.1 0.9 1.2 1.1 1.9 1.2 2.7 1.9 48.3 11.3
4.2 1.3 3.6 0.8 3.1 1.1 4.8 1.6 37.6 9.4
0.86 0.91 0.72 0.90 1.21
(0.61e1.32) (0.79e1.30) (0.63e0.99) (0.89e1.14) (0.75e1.58)
0.038 0.041 0.024 0.045 0.032
113 (42.1) 41 (15.1) 42 (15.7)
140 (51.4) 62 (22.8) 60 (22.1)
0.73 (0.61e0.93) 0.62 (0.32e0.99) 0.58 (0.41e0.89)
0.041 0.028 0.035
20 11 36 0.0
30 18 34 5.0
0.78 (0.56e0.98) 0.65 (0.47e0.78) 1.05 (0.87e1.26) d
0.088 0.062 0.289 d
(7.3) (4.1) (13.4) (0)
(11.2) (6.7) (12.4) (1.8)
OR ¼ odds ratio; CI ¼ confidence interval; QOL ¼ quality of life; GI ¼ gastrointestinal.
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Table 4 Patient Feedback Results Question Are you familiar with clinical pharmacy? (mean SD) Do you know how the clinical pharmacist contributed to your treatment? (mean SD) Are you satisfied with the outcome of this treatment? (mean SD) Would you seek help from a clinical pharmacist in the future? (mean SD)
intervention group on all four questions: 1) Are you familiar with clinical pharmacy? (4.7 0.2 vs. 2.1 0.6, P < 0.001); 2) Do you know how the clinical pharmacist contributed to your treatment? (4.2 0.5 vs. 1.6 0.4, P ¼ 0.027); 3) Are you satisfied with the outcome of this treatment? (4.7 0.2 vs. 3.2 0.4, P ¼ 0.015); and 4) If there was a problem related to drug treatment, would you seek help from a clinical pharmacist? (3.8 0.2 vs. 2.2 0.4, P ¼ 0.006).
Risk Factor Analysis We selected age, sex, ECOG score, pain score, dose titration, combination of opioids, conversion of dosing, follow-up by pharmacists, use of sustained-release morphine tablets, use of controlled-release oxycodone tablets, and use of transdermal fentanyl as independent variables, and adverse events including constipation, nausea, and vomiting as dependent variables for logistic regression analysis. Univariate analysis demonstrated that age, sex, dose titration, combination of opioids, and the specific opioid were possible factors impacting adverse events, and so were included in the multivariate analysis. As shown in Fig. 2, multivariate analysis demonstrated that dose titration (constipation: OR ¼ 0.64, P ¼ 0.027; nausea: OR ¼ 0.62, P ¼ 0.035), follow-up by the pharmacist (constipation: OR ¼ 0.40, P < 0.001; nausea: OR ¼ 0.65, P < 0.001; vomiting: OR ¼ 0.63, P ¼ 0.014), age older than 60 years (OR ¼ 0.71, P ¼ 0.031), and female gender (nausea: OR ¼ 0.64, P ¼ 0.014; vomiting: OR ¼ 0.74, P ¼ 0.035) were independent factors affecting the adverse effects of opioid therapy.
Discussion We report the results of a multicenter, prospective, cohort study comparing the clinical experience of cancer patients receiving
Test Group (N ¼ 259)
Control Group (N ¼ 272)
P-value
4.7 0.2 4.2 0.5
2.1 0.6 1.6 0.4
<0.001 0.027
4.7 0.2 3.8 0.2
3.2 0.4 2.2 0.4
0.015 0.006
intervention from a CPGT with a control group of cancer patients. Results confirmed that clinical pharmacists significantly improved the standardization and efficacy of cancer pain therapy. Clinical pharmacy began in China in the 1980s. In the past 10 years, the Ministry of Health established a system for the training and licensing of clinical pharmacists,18 and this has greatly increased the number of practitioners. There are now more than 20,000 clinical pharmacists in China and the numbers are growing every year.19 Moreover, the roles of clinical pharmacists are expanding. Most large treatment hospitals have practitioners providing guidance for clinical drug administration, pharmacology education, and monitoring of drug use. Pain control is a critical aspect of cancer therapy. Medical institutions around the world are improving cancer pain management by including clinical pharmacists on the treatment team. In Canada, clinical pharmacists actively participate in drug therapy for cancer pain and have contributed enormously to improved outcomes.20 In the U.S., some clinical pharmacists monitor patients after release from the hospital and pain scores have improved significantly.21 In these countries, the clinical pharmacist system is rather mature, and opioids are both frequently used and subject to national guidelines. However, cancer pain management is inconsistent in China. In this study, we established multidisciplinary CPGTs in several Chinese provinces to guide and manage therapy for cancer pain. The clinical pharmacist standardized drug administration through physician education, regular treatment monitoring, and consultation. In addition to routine work, clinical pharmacists also expanded their services. In collaboration with CPGT nurses, the clinical pharmacist conducted regular patient follow-ups to assure correct dosing for efficacy and safety. Each
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Fig. 2. Logistic regression analysis for the risk of opioid-induced a) constipation, b) nausea, and c) vomiting in 542 patients who received opioid analgesics for cancer pain. OR ¼ odds ratio; CI ¼ confidence interval.
team also had administrators to ensure cooperation of the staff and support the normal workflow. Most pharmacist recommendations were accepted directly or after discussion with physicians. The most significant improvements in standardization were 1) more comprehensive pain evaluation, 2) better use of sustained-release tablets and dose titration, 3) a significant decrease in meperidine prescriptions, 4) a significant reduction in polytherapy with two opioids, and 5) more accurate drug conversion. Under the guidance of clinical pharmacists and administrative sanction, physicians recognized the importance of standardized opioid administration and made fewer unnecessary dose increases or complete changes in the opioid therapy.
Because of the enhanced standardization, many patient outcomes were improved. The CPGT group showed significantly better pain control and a reduced rate of adverse events (P < 0.05). No patient in the intervention group became addicted, and we believe that this was related to the reduction in the use of meperidine (Table 3). Logistic regression analysis demonstrated a reduced incidence of nausea, vomiting, and constipation in the CPGT group. However, other side effects such as delirium and skin itch did not improve significantly, but these side effects have proven difficult to prevent in general. Both improvement in pain control and reduction in adverse events likely contributed to the improved patient QOL and better understanding of clinical pharmacists in the CPGT group (Table 3).
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Furthermore, we performed a logistic regression analysis to determine the risks of constipation, nausea, and vomiting (the most common side effects and those most impacting QOL; Fig. 2). The results showed that follow up by the clinical pharmacist were the most significant factor reducing adverse events, followed by dose titration. Female patients and those aged older than 60 years benefited most from monitoring by clinical pharmacists. This analysis underscored the importance of opioid dose monitoring by the clinical pharmacist during follow-up. This study has several limitations. First, patients enrolled could not be randomly assigned. Although baseline data were similar between the intervention and control groups, lack of randomization could still lead to differences in unmeasured confounders, which may partially bias results. Second, abstracting data from the charts and interviewing patients were not blinded as to intervention group, which could lead to some bias in the outcome assessment. Third, some data were only obtained by telephone, which might lead to errors in communication. Thus, we recommend community clinical pharmacists should join these CPGTs and collaborate with hospital-based clinical pharmacists to ensure patient monitoring and education.
Conclusion Despite these limitations, this study confirmed that a multidisciplinary CPGT significantly improved the standardization and efficacy of cancer pain therapy. Thus, the hospital CPGT is a promising treatment model that should be replicated in as many centers as possible.
Disclosures and Acknowledgments This research was supported by the National Nature Science Foundation of China (No. 81301892). The authors sincerely thank the First Affiliated Hospital, College of Medicine, Zhejiang University; Hangzhou Cancer Hospital; The First Hospital of Jiaxing; Beilun People’s Hospital; Shangyu People’s Hospital; People’s Hospital of Xinchang County; Zhengjiang Cancer Hospital; Zhejiang Provincial People’s
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Hospital; Wenzhou Central Hospital; The People’s Hospital of Lishui City; Shenzhou People’s Hospital; Sun Yat-Sen University Cancer Center; Ningbo Eye Hospital;The Second People’s Hospital of Xihu District, Hangzhou; and Taizhou Central Hospital for their participation, support, and guidance during this study.
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