Chemotherapy regimen checks performed by pharmacists contribute to safe administration of chemotherapy

Transcription

1 Original Article Chemotherapy regimen checks performed by pharmacists contribute to safe administration of chemotherapy J Oncol Pharm Practice 2017, Vol. 23(1) 18 25! The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalspermissions.nav DOI: / opp.sagepub.com Shinya Suzuki 1, Alexandre Chan 2,5, Hisanaga Nomura 1, Philip E Johnson 3, Kazushi Endo 4,6 and Shinichiro Saito 1 Abstract Background: Computerized provider order entry (CPOE) has been developed and implemented within cancer center hospitals nationwide in Japan. To ensure that high-quality services are routinely provided by oncology pharmacists, this study was designed to evaluate the interventions through reviewing the orders that are generated by CPOE. Methods: The objective of this retrospective chart review was to evaluate how pharmacists contributed to safe cancer treatment using paper-based pharmacy records. Data were collected from a total of 35,062 chemotherapy regimens for 18,515 outpatients between January and December Results: Of these 35,062 chemotherapy regimens, the rate of pharmacists interventions was 1.1% (n ¼ 408). Among them, 53.1% (217/408) of the chemotherapy prescriptions were modified due to pharmacist interventions. The reasons for interventions included changes in the chemotherapy regimen were unclear in 49.5%, physicians prescription errors (22.0%), pharmacist suggestions to improve chemotherapy (15.1%), and finding differences between physicians chemotherapy records and their chemotherapy prescriptions (13.2%). The top three reasons for the 217 prescription modifications due to pharmacist interventions were finding prescription errors (34.5%), reasons for change in the chemotherapy regimen were unclear (32.7%), and finding differences between physicians chemotherapy records and their chemotherapy prescriptions (28.5%). Conclusion: The computer could not evaluate chemotherapy protocols or adjust doses of anticancer medicines according to patients conditions. Therefore, oncology pharmacists should continue to ensure safe and appropriate administration of cancer chemotherapy. Keywords Pharmacy intervention, cancer chemotherapy, prescription errors Introduction A medication error is defined as any error that arises in the process of medication use. 1 Within oncology pharmacy practices, pharmacists play a substantial role in reviewing and checking chemotherapy-containing prescriptions, because chemotherapy agents are inherently toxic, thus highlighting the need to be vigilant to prevent medication errors. With the use of technology in contemporary clinical practice, such as computerized provider order entry (CPOE), there has been a sharp reduction of medication errors. 2 The benefits of CPOE for safe cancer chemotherapy administration have been previously reported in Japan. 3,4 However, prescribers may not favor the usage of CPOE for various logistical reasons. 5 In Japan, CPOE has been developed and implemented within cancer center hospitals nationwide. At the National Cancer Center Hospital East (NCCHE), the division of pharmacy has introduced CPOE to ensure safe administration and to validate cancer 1 Division of Pharmacy, National Cancer Center Hospital East, National Research and Development Agency, Kashiwa, Japan 2 Department of Pharmacy, National University of Singapore, Singapore, Singapore 3 Director of Pharmacy (Retired), Moffitt Cancer Center, Tampa, FL, USA 4 Japanese Society of Hospital Pharmacists, Tokyo, Japan 5 Oncology Pharmacy, National Cancer Centre Singapore, Singapore 6 Department of Drug Safety Management, Meiji Pharmaceutical University, Tokyo, Japan Corresponding author: Shinya Suzuki, Division of Pharmacy, National Cancer Center Hospital East, National Research and Development Agency, Kashiwanoha, Kashiwa, Chiba , Japan. ssuzuki@east.ncc.go.jp

2 Suzuki et al. 19 chemotherapy since The CPOE system provides template formats which are used for anticancer drugs and any premedication and supportive drugs. The CPOE template is programmed for checking the dose and anticancer medicines and the chemotherapy interval. The drug protocols are developed by oncologists who submitted their chemotherapy regimens to the pharmacy division. The pharmacy division has a role to evaluate the validity of the chemotherapy. After the reviewing process, the pharmacy division builds the protocol into the order template in the CPOE system. After the template is approved, the oncologist only needs to choose the name of a chemotherapy regimen to order the chemotherapy on each patient s electronic medical record (EMR). The CPOE utilizes weight and height to calculate dose of chemotherapy regimens and the template provides the sequence for anticancer agents, along with supportive medicines and hydration, which oncologists have authorized for the specific protocol. The final templates are approved by a committee that is comprised of oncologists and pharmacists. CPOE also allows oncologists to select their choice of anticancer drugs and infusion bags, calculate drug dosages and administration rates, include appropriate supportive medicines, and schedule the administration of these drugs accordingly. An EMR and an electronic medication administration record (emar) are also incorporated in order to enable medical professionals to check critical components. In addition, the computerized system provides print labels and prescriptions that are easier to read and thus safer than handwritten prescriptions. To ensure that high-quality services are routinely provided by oncology pharmacists at NCCHE, this study was designed to evaluate the interventions that were conducted by Japanese oncology pharmacists by reviewing the orders that were generated by the CPOE. Methods Study design The current study was a single-center, retrospective review of pharmacy records at the NCCHE between January and December The data do not contain patients personal information, since information was recorded by the pharmacists in such a manner that subjects were deidentified. Therefore, this study was exempted from full review by the institutional review board. Settings The NCCHE is one of two national center hospitals for cancer treatment in Japan. It has a leadership function and plays an important role in cancer medicine. The NCCHE, a 425-bed cancer-specific hospital, serves about 1000 inpatients and approximately 20,000 outpatients per month. The NCCHE pharmacy division currently registers about 400 chemotherapy regimen templates on the CPOE. Among the 10 pharmacists at NCCHE, four are routinely involved with chemotherapy checking. At the NCCHE, a board-certified oncology pharmacist must perform the final review in the chemotherapy dispensing process. Workflow All chemotherapy agents are prescribed through CPOE. The pharmacy division used the IBM MIRACL Õ (until the beginning of May 2013) and the Fujitsu MISSION Õ systems (after May 2013) as their CPOE. The CPOE provides chemotherapy templates, which consist of registered anticancer drugs and any premedication and supportive drugs. The CPOE provides checking of the dose and anticancer medicines and the chemotherapy interval. The system also provides printed prescriptions and labels; the pharmacy division does not accept handwritten anticancer prescriptions for risk management purposes. In addition to the computer system, the division has also created a paper-based pharmacy record (Figure 1) to document a pharmacist s evaluation of the chemotherapy order. This paper-based pharmacy record is a tool that supports an oncology pharmacist s chemotherapy evaluation. The paper-based pharmacy record s evaluation items are: (1) dose of anticancer medicine; (2) interval; (3) indication for the regimen; (4) administration rates; and (5) premedication, hydration, and supportive medicines (Figure 1). In addition to the check using the record, a pharmacist suggests appropriate bags for each anticancer injection along with administration rates and routes for the regimen and enters the information in the emar and EMR. The paper record is an independent tool from the EMR/eMAR. The pharmacists check the chemotherapy using the paper tool and information from the EMR/eMAR. The information originates from the CPOE and EMR/eMAR, however, the checking process is not performed digitally. The hand writing paper-based pharmacy check record allows the pharmacists to follow in the treatment progress each chemotherapy cycles. As described in Figure 1, the paper record is a tool to summarize the chemotherapy history. Before chemotherapy is compounded, a pharmacist prepares the medicines and also checks the chemotherapy regimen prescriptions using the paperbased pharmacy record. A second pharmacist checks the paper-based pharmacy record before the chemotherapy is prepared. After the completion of the double check, the prescription review process in the pharmacy division is considered completed (Figure 2).

3 20 Journal of Oncology Pharmacy Practice 23(1) Figure 1. An example of a paper-based pharmacy record (FOLFOX + bevacizumab).

4 Suzuki et al. 21 Definitions and endpoints Interventions by pharmacists. The pharmacy division recorded all pharmacy interventions, which included order clarifications or recommendations made by pharmacists. The record consisted of the prescribing date, name of the clinician, contents of the intervention, and whether or not the clinician changed the prescription. The incidence of pharmacists interventions and the incidence of prescriptions that required modification due to the pharmacists interventions were evaluated. These endpoints were chosen because the aim was to capture the number of interventions required by pharmacists through reviewing the prescriptions that are generated by CPOE. Reasons for pharmacists interventions. In order to categorize the interventions, the reasons for interventions were classified into categories depending on the purposes of the interventions. These included: reasons for change in the chemotherapy regimen were unclear, prescription errors, pharmacist suggestions to improve chemotherapy, and differences between physicians chemotherapy records and their chemotherapy prescriptions. Pharmacists interventions. The types of interventions were classified into categories depending on the focus of the interventions. These included: dose of anticancer drugs, adding/stopping anticancer drugs, premedication/ supportive medicine, anticancer drug dose less than 95% calculated, interval, chemotherapy regimen choice, administration routes/rates, bag of anticancer drugs, dose according to weight change, dose rounding, and suggesting laboratory test. Adding/stopping anticancer drugs was defined as interventions that a pharmacist found a physician added or stopped anticancer drugs in a chemotherapy regimen without reasonable reasons. Chemotherapy regimen choice was defined as interventions that a pharmacist found a wrong chemotherapy regimen prescription for a patient. Bag of anticancer drugs was defined as interventions that a pharmacist suggested an appropriate infusion solution for chemotherapy agents in a chemotherapy regimen prescription. Dose according to weight change was defined as interventions in which a pharmacist suggested recalculation due to significant weight change from a previous chemotherapy regimen prescription. Dose rounding was defined as interventions in which a pharmacist found a rounding error, such as an anticancer drug dose less than 95% calculated. Data analysis Descriptive statistics were used to examine the mean number and frequency of prescription modifications due to pharmacy interventions. All calculations were performed using Microsoft Õ Excel Results Number and frequency of chemotherapy prescription modifications due to pharmacists interventions A total of 35,062 chemotherapy regimens for 18,515 patients were analyzed during the 12-month study period. The average number of chemotherapy administrations was [S.D.] per month. The average number of patients was [S.D.] per month. It was noted that the number of pharmacist s interventions was different each month. In particular, there were a significantly higher number of inquiries in May 2013 compared to other months (Figure 3). This is because the replacement of the IBM MIRACL Õ system with Fujitsu MISSION Õ took place that month. During that period, clinicians and pharmacists were troubleshooting the new CPOE system, and the paper-based pharmacy record played a significant and integral role in checking and reviewing chemotherapy administration. Of the 35,062 administered chemotherapy regimens, the proportion of orders requiring clarification was 1.1% (total 408 pharmacists interventions). Order chemotherapy Physician CPOE Input Output Prescription label Pharmacist A Dispense anticancer agents and premedications, etc. Check the chemotherapy using paper-based pharmacy record Pharmacist B Double check the paper-based pharmacy record and then, compound anticancer medicines Figure 2. Workflow.

5 22 Journal of Oncology Pharmacy Practice 23(1) 3,500 3,000 2,908 2,765 2,831 3,105 3,167 2,647 2,954 2,687 2,918 3,146 2,963 2,971 2,500 2,000 1,500 1, Modification rates 1,573 1,519 1,573 1,628 1, ,345 59% 33% 46% 46% 80% 43% 26% 33% 85% 48% 54% 32% 1,567 Number of chemotherapy regimens 1,487 1,453 1,648 Number of patients (N=18,515) 1,528 1,566 Number of inquiries (N=408) Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Figure 3. Number of chemotherapy regimens, number of pharmacist inquiries, and modification rates. Table 1. Pharmacist s interventions (n ¼ 408). Reasons for change in the chemotherapy regimen were unclear Finding prescription errors Pharmacist suggestions to improve chemotherapy Finding differences between physicians chemotherapy records and their chemotherapy prescriptions Total Number of interventions n (%) n (%) n (%) n (%) n (%) Dose of anticancer drugs 114 (27.9%) 35 (8.6%) 5 (1.2%) 25 (6.1%) 179 (43.9%) Adding/stopping anticancer drugs 37 (9.1%) 5 (1.2%) 1 (0.2%) 14 (3.4%) 57 (14.0%) Premedication/supportive medicine 16 (3.9%) 26 (6.4%) 29 (7.1%) 7 (1.7%) 78 (19.1%) Anticancer drug dose 11 (2.7%) (2.7%) less than 95% calculated Changes of treatment interval 12 (2.9%) 3 (0.7%) 0 6 (1.5%) 21 (5.1%) Chemotherapy regimen choice 6 (1.5%) 5 (1.2%) 0 1 (0.2%) 12 (2.9%) Administration routes/rates 5 (1.2%) 9 (2.2%) 0 1 (0.2%) 15 (3.7%) Chemotherapy administration 1 (0.2%) 1 (0.2%) 4 (1.0%) 0 6 (1.5%) Bag of anticancer drugs 0 6 (1.5%) 1 (0.2%) 0 7 (1.7%) Dose according to weight change (2.9%) 0 12 (2.9%) Dose rounding (1.7%) 0 7 (1.7%) Suggesting laboratory test (0.7%) 0 3 (0.7%) Total 202 (49.5%) 90 (22.1%) 62 (15.2%) 54 (13.2%) 408 Among the 408 interventions, the proportion of interventions accepted by prescribers was 53.1% (217/408). Reasons for interventions Reasons for pharmacists interventions were as follows: reasons for change in the chemotherapy regimen were unclear in 49.5% (n ¼ 202); physicians prescription errors in 22.0% (n ¼ 90); pharmacist suggestions to improve chemotherapy in 15.1% (n ¼ 62); and finding differences between physicians chemotherapy records and their chemotherapy prescriptions in 13.2% (n ¼ 54) (Table 1). Of the total 408 interventions, the number of important interventions, such as reasons for change in the chemotherapy regimen were unclear, physicians prescription errors, and finding differences between physicians chemotherapy records and their chemotherapy prescriptions, was 346 (84.8%). The number of prescription modifications events was 177 (51.1%). This means the pharmacists interventions clarified the reasons for the remaining 169 (48.9%) prescriptions.

6 Suzuki et al. 23 Pharmacists interventions Among the 408 pharmacists clarifications or recommendations that were made over the study period, the subjects of pharmacists interventions included: anticancer drug doses, n ¼ 179 (43.9%), premedication/supportive medicine, n ¼ 78 (19.1%), adding/stopping anticancer drugs, n ¼ 57 (14.0%), and others, including dose rounding, interval of chemotherapy, chemotherapy regimen choice, administration routes/rates, chemotherapy administration, bag of anticancer drugs, dose according to weight change, dose rounding, and suggesting laboratory test. Of 408 pharmacy clarifications or recommendations, anticancer drug doses (43.9%), adding/stopping anticancer drugs (14.0%), and chemotherapy regimen choice (2.9%) were obviously critical, and their cumulative total was more than half of the pharmacists interventions. Frequency of chemotherapy prescription modifications due to pharmacists interventions A total of 217 prescriptions were modified due to pharmacists interventions for the following reasons: reasons for change in the chemotherapy regimen were unclear in 32.7% (n ¼ 71), finding prescription errors in 34.5% (n ¼ 75), pharmacist suggestions to improve chemotherapy in 18.4% (n ¼ 40), and finding differences between physicians chemotherapy records and their chemotherapy prescriptions in 28.5% (n ¼ 31) (Table 2). Of the total 202 pharmacists interventions due to reasons for change in the chemotherapy regimen were unclear, the frequency of chemotherapy prescription modifications due to pharmacists interventions was high for premedication/supportive medicine (75.0%) and dose of anticancer drugs (39.5%). Of the total 90 pharmacists interventions due to finding prescription errors, the frequency of chemotherapy prescription modifications due to pharmacists interventions was high for dose of anticancer drugs (82.9%) and premedication/supportive medicine (84.6%). Of the total 62 pharmacists interventions due to pharmacist suggestions to improve chemotherapy, the frequency of chemotherapy prescription modifications due to pharmacists interventions was high for premedication/supportive medicine (82.7%). Of the total 54 pharmacist s interventions due to finding prescription errors, the frequency of chemotherapy prescription modifications due to pharmacists interventions was high for dose of anticancer drugs (56.0%), adding/ stopping anticancer drugs (64.3%), and for premedication/supportive medicine (85.7%). Discussion In this retrospective 12-month chart review study, of the 408 documented interventions, the rate of interventions accepted by prescribers was 53.1% (217/408). More than half of the interventions were related to critical issues, such as choice of chemotherapy agents and their doses. Although not all pharmacists interventions were accepted by doctors, most of the inquiries were related to usage or dose of anticancer agents. Table 2. Types of prescriptions in which interventions were successful (n ¼ 217). Reasons for change in the chemotherapy regimen were unclear Finding prescription errors Pharmacist suggestions to improve chemotherapy Finding differences between physicians chemotherapy records and their chemotherapy prescriptions Total Number of modifications/number n/n (%) n/n (%) n/n (%) n/n (%) n/n (%) of interventions (%) Dose of anticancer drugs 45/114 (39.5%) 29/35 (82.9%) 2/5 (40.0%) 14/25 (56.0%) 90/179 (50.3%) Adding/stopping anticancer drugs 8/37 (21.6%) 4/5 (80.0%) 1/1 (100%) 9/14 (64.3%) 22/57 (38.6%) Premedication/supportive medicine 12/16 (75.0%) 22/26 (84.6%) 24/29 (82.7%) 6/7 (85.7%) 64/78 (82.1%) Anticancer drug dose less 1/11 (9.1%) /11 (9.1%) than 95% calculated Changes of treatment interval 1/12 (8.3%) 1/3 (33.3%) 0 1/6 (16.7%) 3/21 (14.3%) Chemotherapy regimen choice 1/6 (16.7%) 3/5 (60.0%) 0 0/1 (0%) 4/12 (33.3%) Administration routes/rates 3/5 (60.0%) 9/9 (100%) 0 1/1 (100%) 13/15 (86.7%) Chemotherapy administration 0/1 (0%) 1/1 (100%) 0/4 (0%) 0 1/6 (16.7%) Bag of anticancer drugs 0 6/6 (100%) 0/1 (0%) 0 6/7 (85.7%) Dose according to weight change 0 0 3/12 (25.0%) 0 3/12 (25.0%) Dose rounding 0 0 7/7 (100%) 0 7/7 (100%) Suggesting laboratory test 0 0 3/3 (100%) 0 3/3 (100%) Total 71/202 (35.1%) 75/90 (83.3%) 40/62 (64.5%) 31/54 (57.4%) 217/408 (53.2%)

7 24 Journal of Oncology Pharmacy Practice 23(1) More than half of the interventions for oncologists were due to insufficient descriptions of their cancer chemotherapy prescription. In fact, of the total 408 interventions, 84.8% were for critical issues, reasons for change in the chemotherapy regimen were unclear, physicians prescription errors, and finding differences between physicians chemotherapy records and their chemotherapy prescriptions. For critical issues, they are generally referred to the ISMP International Medication Safety Self Assessment Õ for Oncology. Even though modifications occurred in only 51.1%, the pharmacists intervention clarified the reasons for the remaining 169 (48.9%) prescriptions. The number of interventions required for each month ranged widely from 6 to 83. The number of interventions was especially high, particularly when the NCCHE introduced a new CPOE system. All pharmacy interventions were for physicians chemotherapy prescriptions ordered via a sophisticated CPOE system. The results showed there were certain errors in the prescriptions that were prevented by pharmacists review before chemotherapy. Previously, the pharmacy division of NCCHE reported the effects of clinical pharmacist interventions, 6 8 but those reports were about patients pharmaceutical care after the chemotherapy prescriptions. The results of this study showed that mistakes are inevitable in physicians prescriptions, even though CPOE was used to prescribe chemotherapy. Numerous reports concluded that pharmacist interventions are beneficial in clinical settings, but the time to review prescription processes is generally limited and medication errors are potentially fatal Of all of the pharmacists inquiries, approximately 20% were pharmacist suggestions to improve chemotherapy by referring to patients previous chemotherapy, and approximately 80% were inquiries regarding the validity of the oncologists chemotherapy prescriptions. Our goal is to have sufficient checks and verifications, so all errors are corrected before chemotherapy is administered to the patient. Chemotherapy regimen prescription errors included the doses of anticancer drugs, intervals, adding or stopping anticancer drugs, chemotherapy regimen choice, and administration routes or rates, and these errors could have fatal consequences. 17 It is important to note that CPOE does not prevent all types of prescription errors, even with simple prescribing mistakes, because the computer system is unable to identify or judge the validity of the chemotherapy regimens. CPOE is only able to perform checks on basic items, such as dose calculation and the interval of chemotherapy. The CPOE system is able to recognize dose calculations and standard administration for each anticancer drug, but it is still impossible for computers to evaluate cancer treatment according to adverse drug reactions, patients conditions, and treatment strategies of cancer chemotherapy, because these factors are not countable and measureable. In the present study, even though the prescription modification rate was not high, interventions were still required with prescriptions that were ordered with CPOE. This suggests that CPOE was unable to prevent components that required medical or pharmaceutical judgement, such as the indications for anticancer agents, dose modification of chemotherapy, and the strategic plan for cancer treatment. For example, adding or reducing anticancer agents and changes in regimens require reasonable and logical decisions by oncologists and pharmacists. Moreover, the computer could not check the validity and accuracy of dose reductions, interval changes, and the choice of chemotherapy, even though the computer order entry system regulated the dose and interval of cancer chemotherapy. There are several limitations in this study. The study showed how pharmacists picked up prescription errors using paper-based pharmacy records and reduced prescription errors, but the study could not show the actual number and percentage of errors prevented by CPOE. In addition, this was a retrospective study, and the data might be under-reported because the pharmacist may fail to recall some interventions they made when they completed their reports. This study did not investigate whether certain characteristics can predict the occurrence of errors. Future studies should investigate whether certain characteristics are able to early identify problems within the dispensing process in order to improve the efficiency of the dispensing process. Conclusions This is the first study to evaluate interventions that were conducted by Japanese oncology pharmacists by reviewing the orders that are generated by CPOE. CPOE could not evaluate chemotherapy protocols or adjust doses of anticancer medicines according to patients conditions. Therefore, pharmacists who check prescriptions need to be knowledgable of the chemotherapy to conduct safe cancer chemotherapy. Data from this study suggest that prescriptions ordered through CPOE are not foolproof, and oncology pharmacists should continue to ensure safe and adequate administration of cancer chemotherapy. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Funding The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research received no specific grant from any

8 Suzuki et al. 25 funding agency in the public, commercial, or not-for-profit sectors. References 1. Bates DW, Boyle DL, Vliet MVV, et al. Relationship between medication errors and adverse drug events. J Gen Intern Med 1995; 10: Jacobson JO, Polovich M, Gilmore TR, et al. Revisions to the 2009 American Society of clinical oncology/oncology nursing society chemotherapy administration safety standards: Expanding the scope to include inpatient settings. J Oncol Pract 2012; 8: Nakashima M and Sugiyama T. A survey of journal articles related to computerized support systems for cancer chemotherapy in Journal of Japanese Society of Hospital Pharmacists and Japanese Journal of Pharmaceutical Health Care and Science. J Jap Soc Health Care Manage 2014; 15: Nakashima M. Studies regarding quality enhancement of affairs by pharmacist and clinical evaluation of cancer chemotherapy. Jpn J Pharm Health Care Sci 2015; 41: Bubalo J, Warden BA, Wiegel JJ, et al. Does applying technology throughout the medication use process improve patient safety with antineoplastics? J Oncol Pharm Pract 2014; 20: Suzuki S, Muranaga A, Matsui R, et al. Adherence in use of oral antibiotics for fever in outpatient docetaxel chemotherapy. Jpn J Pharm Health Care Sci 2011; 37: Suzuki S, Enokida T, Kobayashi T, et al. Evaluation of the impact of a flowchart-type leaflet for cancer inpatients. SAGE Open Med 2014; 2: Suzuki S, Odanaka M, Funazaki H, et al. Evaluation of improvement of adherence following pharmacist intervention for hand/foot skin reactions induced by sorafenib. Jpn J Pharm Health Care Sci 2011; 37: Schnipper JL, Kirwin JL, Cotugno MC, et al. Role of pharmacist counseling in preventing adverse drug events after hospitalization. Arch Intern Med 2006; 166: Read H, Ladds S, Rhodes B, et al. The impact of a supplementary medication review and counselling service within the oncology outpatient setting. Br J Cancer 2007; 96: Phansalkar S, Hoffman JM, Nebeker JR, et al. Pharmacists versus nonpharmacists in adverse drug event detection: A meta-analysis and systematic review. Am J Health Syst Pharm 2007; 64: McMullin ST, Hennenfent JA, Ritchie DJ, et al. A prospective, randomized trial to assess the cost impact of pharmacist-initiated interventions. Arch Intern Med 1999; 159: Lynn MA. Pharmacist interventions in pain management. Am J Health Syst Pharm 2004; 61: Condren ME, Haase MR, Luedtke SA, et al. Clinical activities of an academic pediatric pharmacy team. Ann Pharmacother 2004; 38: Bond CA and Raehl CL. Clinical pharmacy services, pharmacy staffing, and hospital mortality rates. Pharmacotherapy 2007; 27: Bond CA and Raehl CL. Clinical pharmacy services, pharmacy staffing, and adverse drug reactions in United States hospitals. Pharmacotherapy 2006; 26: Ranchon F, You B, Salles G, et al. Improving cancer patient care with combined medication error reviews and morbidity and mortality conferences. Chemotherapy 2013; 59: