Computerized prescriber order entry (CPOE) systems consistently rank among the most important technologies in the pharmacy, and adoption rates have increased exponentially in recent years. In 2007, only 15% of hospital pharmacies employed this tool, but by 2014, the adoption rate reached 86%.¹ This dramatic increase is heartening, given the potential for error when using manual ordering processes (see SIDEBAR). 

CPOE is particularly useful for chemotherapy ordering, as antineoplastic agents have complex dosing schedules and narrow therapeutic windows and are highly toxic, even at FDA-approved dosages and administration schedules.^2-5 In addition, dose adjustments and interactions with other medications are common. Thus, standardizing chemotherapy orders for CPOE is vital to ensuring patient safety.

The Ohio State University Comprehensive Cancer Center—James Cancer Hospital (The James) ranks as one of the top cancer hospitals in the nation and is a member of the National Comprehensive Cancer Network (NCCN), the Alliance of Dedicated Cancer Centers, and the National Cancer Institute. In anticipation of a 20% increase in admissions to The James over the next 10 years, the hospital opened a new cancer center tower in December, 2014. This building contains 276 adult cancer beds, a 24-bed hematological transplant unit, 30 cancer critical care beds, an outpatient chemotherapy infusion pharmacy, and its own cancer-specific emergency department. The pharmacy department employs inpatient and outpatient hematology/oncology clinical specialist pharmacists, pain and palliative medicine specialist pharmacists, anticoagulation specialist pharmacists, cancer informatics pharmacists, medication assistance pharmacists, and hematology/oncology pharmacy residents. Since ordering and dispensing high-risk chemotherapy agents is our core business, using a robust CPOE system to ensure accurate medication ordering is imperative, and standardizing chemotherapy orders for CPOE is a critical function for the safe delivery of these medications.

Benefits of CPOE Systems 
CPOE systems ensure accurate prescribing by precluding errors related to transcription and illegible handwritten orders.^2,4,5 In addition, they offer features such as: 

• Up-to-date information on formulary status and approved regimens6
• Automated calculation of drug doses and rates²
• Alert functions, including warnings in case of overdose or critical values missing for dosage calculations²
• Automatic scheduling of multiple-day treatments and repeating treatment cycles^2,4

When integrated with clinical decision support (CDS) systems, CPOE can provide recommendations for dose adjustments based on laboratory results, as well as suggest alternate regimens that could be used, or identify regimens that should be avoided, based on patient clinical factors.⁶ In addition, users can program CDS systems to notify prescribers of potential drug-drug, drug-disease, and drug-allergy interactions and when ordered doses exceed predetermined limits.⁶

Another significant benefit of CPOE is that oncology providers no longer need to memorize complex formulas, such as those used to calculate body surface area (BSA), creatinine clearance (ie, Cockroft-Gault equation, Jeliffe formula),^3,6 and AUC dose; likewise, cumulative dose tracking is automated. CPOE automatically uses the information documented in the chart, including lab results, to perform these and other calculations. 

In addition, CPOE ensures that chemotherapy is ordered in accordance with recognized national standards. Because guidelines change over time, having oncology regimens available electronically makes updating order sets easier. References to supporting primary literature can be integrated into the treatment plans, and links can be added at the point of prescribing to provide convenient access to additional online resources. Furthermore, electronic ordering systems can be programmed to ensure that prescribers do not use outdated and/or unapproved order forms and do not select inappropriate dosage forms, routes, or frequencies. 

Standardizing Chemotherapy Orders 
Building chemotherapy regimens correctly before implementing CPOE is crucial. Well-designed, standardized medication orders eliminate many of the problems related to misinterpretation by organizing treatment information in a clear, consistent, and uniform format.² Studies show that using standardized chemotherapy regimens reduce the annual incidence of prescribing errors per 1000 chemotherapy doses by 50%.³ However, health care providers should be cognizant that interpretation errors still may occur, as automation is not a replacement for personal vigilance.

Standardizing chemotherapy orders is a challenging endeavor, particularly for institutions with multiple sites and practices. Developing a multidisciplinary standardization team,⁷ or using the pharmacy and therapeutics (P&T) executive committee to make decisions about treatment plan content and workflows, is necessary to begin the process.^2,6 At The James, the hematology/oncology P&T subcommittee (which reports to the medical staff advisory committee) makes these decisions. This committee meets on a monthly basis and comprises advanced level providers, oncology physicians, pharmacists, and nurses. The committee uses a formal process to evaluate new drugs and treatment regimens, as well as any use of chemotherapy for off-label indications, to ensure that all chemotherapy treatment plan content is supported by clinical evidence. 

When standardizing chemotherapy orders, it is important to identify all order forms currently in use at the hospital.^2,5,6 Collaborating with the informatics team, as well as the institution’s forms committee (if oncology order sets are in hard copy), is crucial during this process. The P&T committee is responsible for conducting a comprehensive review of existing order sets to determine which regimens can be consolidated, which ones require additional evidence to support practice, which can be eliminated, and which meet all necessary requirements. 

Executive leadership should support the standardization project by ensuring that oncology providers and pharmacists have the time necessary to conduct a robust review of all existing order sets.⁷ The content review should rely on national guidelines, such as those from NCCN and the American Society of Clinical Oncology (ASCO),^8,9 and should facilitate establishing practice guidelines (eg, dose ceilings, route restrictions, supportive care, dosing calculations, and adjustments). Review should occur on a sustainable, ongoing basis to ensure that content reflects updated guidelines and newly approved agents and treatment regimens. The Institute for Safe Medication Practices (ISMP) recommends that a multidisciplinary team reviews order sets at least every 2 years.¹⁰ 

At a minimum, each chemotherapy treatment plan should include patient name, medical record number, date the order was prescribed, time and date that the chemotherapy is to be administered, patient-specific values (eg, height, weight, BSA), the planned medication dosage and administration rate, patient allergies and medication history, and the prescriber’s name and signature.^2,4,10-12 Chemotherapy regimens and medication orders should indicate the patient weight used to calculate drug doses and identify the equation used.^2,4,12 Be sure to use the generic name when ordering antineoplastic agents.¹⁰ In addition, specify dosage form, the calculated drug dosage, the administration rate and route, the interval between doses, the days when the doses should be administered, the total length of the cycle, and the date and time when treatment should begin.^2,4,12 All of these are forced functions in The James’ CPOE system.

Elements of an Effective Order Entry System
When evaluating the various CPOE options, consider the following features: 

• Restricting Chemotherapy Ordering Access. Data have shown that chemotherapy ordering by inexperienced users is a risk factor for prescribing errors.¹¹ An effective electronic chemotherapy ordering system permits limiting the users who are authorized to order antineoplastic agents and electronically records when users enter, change, and discontinue orders.² In addition, the CPOE system should allow providers to review and verify orders before initiating treatment.²
• Standardized Body Weight Calculations. A chemotherapy CPOE system should facilitate standardized methods for calculating BSA and ideal body weight (IBW), rounding calculated results, and changing dosages and administration rates in response to changes in patients’ heights and weights.^2,4,12 Treatment plans and medication orders should clearly indicate the weight and equations used in calculating drug dosages.^4,12 
• Flexible Order Regimen Formats. When selecting an order entry system for oncology use, it is important that the system allow for ordering regimens in terms of cycles and days.^2,4,10,12 The system should facilitate sequencing medication^2,12 and procedure orders within the regimen and should display the information in a uniform format that is easy to read and understand. One way is to use categories (eg, treatment parameters, hydration, pre-medications, chemotherapy, hypersensitivity reaction orders, etc) to separate the information in a logical manner. CPOE also should facilitate patient staging workflows and reporting to national registries.
• Robust Medication Monitoring Capabilities. Medication monitoring is an important component of chemotherapy administration. CPOE should alert prescribers to laboratory values that are out of range and provide dosing recommendations based on lab results.^2,6 Some existing oncology systems even suggest oncology regimens based on built-in pathways that search for pre-defined patient and/or disease-specific parameters. 
• Intuitive Interface. Evaluate the usability of the chemotherapy CPOE system to avoid complex and unintuitive user interfaces and cluttered or poorly designed displays.¹³ The system should facilitate interprofessional communication and task coordination. 
• Advanced Forced Function Capacity. Forced functions—features of a system that allow only correct prescribing—are a valuable tool to ensure dosing accuracy.⁵ Constraints should be developed to limit maximum antineoplastic drug dosages, administration routes, frequencies, and schedules. Limits also should be established for the maximum amount of antineoplastic medication that may be administered during one treatment course or cycle and, when appropriate, the maximum lifetime dosage.² Ideally, the computer software should alert health care providers whenever an order for an antineoplastic medication exceeds defined limits.
  
  For example, a forced function can be set to prevent vincristine from being ordered intrathecally. In addition, most of the time the dose of vincristine should not exceed 2 mg; if an ordered dose exceeds this limit, the system should notify providers and prevent ordering. However, there are certain circumstances when a 2-mg dose might be appropriate; at The James we have configured the system to allow ordering more than 2 mg of vincristine for these situations.

• Workflows for Specific Patient Populations. The system should facilitate workflows based on specific patient populations, such as pediatric and obese patients. Some disease groups cap their maximum BSA, whereas others do not. For example, the gynecology oncology group integrates BMI into the dosing weight criteria for patients receiving carboplatin. CPOE should be sufficiently flexible to accommodate such individualized formulas.

Oral Chemotherapy
In recent years, multiple oral chemotherapy agents have been approved, and the number of oral chemotherapeutic agents in the development pipeline is increasing.¹⁴ Despite potential safety risks, a survey of US comprehensive cancer centers found that prescribers are adopting fewer safety standards surrounding the use of oral chemotherapy agents compared with infusion chemotherapy.¹⁵ Significant practice gaps in both the prescribing and monitoring of oral chemotherapy treatments were identified, with one of the main issues being a lack of required prescription elements (eg, diagnosis, protocol, cycle number, dose calculations, etc).¹⁵ 

CPOE can help correct this problem by employing standardized order sets. In addition, it can facilitate safety by setting limits on who can order oral chemotherapeutic agents within the system, providing CDS alerts, eliminating issues with illegible/incomplete handwritten prescriptions, and reducing errors in the number of pills supplied (eg, with complicated week on/off dosing schedules or when combining different pill strengths to yield the appropriate dose).¹⁴ 

Clinical Trials and CPOE
It is important that hospitals participating in clinical trials and employing CPOE facilitate research workflows by enrolling patients and linking their regimens to research studies. CPOE systems should allow flagging such patients to help identify treatments or procedures that could be contraindicated by study designs.² Because research studies often require specific drug sequencing, infusion durations, dose reduction, or medication preparation, the system should allow full customization of order sets and medication build. CPOE also can be used to identify commercially supplied versus study supplied products and route correct charging based on this information.

Conclusion
Prescribing, dispensing, and administering chemotherapy are high-risk processes that should be developed according to evidence-based guidelines and best practices. A robust oncology CPOE system can provide the necessary tools to prevent potentially fatal medication events. The success of CPOE implementation depends on its design, quality, and functionality, as well as on staff training and competency and communication among its users.

Janinah S. Barreto, PharmD, MS, completed a Doctor of Pharmacy program at the college of pharmacy of the University of Puerto Rico, Medical Science Campus. She later completed a PGY2 residency and a Masters in Health System Pharmacy Administration at The Ohio State University (OSU). Janinah served 3 years as the medication safety pharmacist for the OSU health system and is now the pharmacy manager for oncology informatics at The James Cancer Hospital. In her current role, she oversees a multidisciplinary team of pharmacy and nursing informatics builders; coordinates oncology order set development; and oversees all build, configuration, and maintenance for oncology and research items.

Niesha Griffith, MS, RPh, FASHP, is administrator of oncology pharmacy and infusion services for The James Cancer Hospital at OSU. She graduated from the OSU College of Pharmacy in 1996 from the combined MS in hospital pharmacy administration/residency program. Niesha is responsible for managing inpatient and outpatient oncology pharmacy services for The James Cancer Hospital, including management of five outpatient chemotherapy infusion pharmacies, eight outpatient infusion areas, inpatient and outpatient clinical pharmacy services, educational and research programs, and the institutions’ medication assistance programs. She is the immediate past president of the Hematology/Oncology Pharmacy Association.

References

1. The 9th Annual State of Pharmacy Automation. CPOE. Pharm Purch Prod. 2014;11(8):30-32.
2. ASHP Council on Professional Affairs. ASHP guidelines on preventing medication errors with antineoplastic agents. Am J Health-Syst Pharm. 2002;59(17):1648–1668. 
3. Elsaid K, Truong T, Monckeberg M, et al. Impact of electronic chemotherapy order forms on prescribing errors at an urban medical center: results from an interrupted time-series analysis. Int J Qual Health Care. 2013;25(6):656–663.
4. 4. Carrington C, Stone L, Koczwara B, et al. The Clinical Oncological Society of Australia (COSA) guidelines for the safe prescribing, dispensing and administration of cancer chemotherapy. Asia Pac J Clin Oncol. 2010;6(3):220-237. 
5. Cohen MR. Preventing medication errors in cancer chemotherapy. In: Cohen MR, ed. Medication Errors. 2nd ed. Washington, DC: APhA; 2007:445-468.
6. ASHP guidelines on pharmacy planning for implementation of computerized provider order entry systems in hospitals and health systems. Automation and Information Technology Section Guidelines. http://www.ashp.org/doclibrary/bestpractices/autoitgdlcpoe.aspx. Accessed October 17, 2014.
7. Adelson KB, Qiu YC, Evangelista M, et al. Implementation of electronic chemotherapy ordering: an opportunity to improve evidence-based oncology care. J Oncol Pract. 2014;10(2):e113-e119.
8. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology (NCCN Guidelines). http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed October 17, 2014.
9. American Society of Clinical Oncology Guidelines. http://www.asco.org/guidelines. Accessed October 17, 2014.
10. ISMP Guidelines for Standard Order Sets (2010). Institute for Safe Medication Practice Web site. http://www.ismp.org/tools/guidelines/standardordersets.pdf. Accessed October 17, 2014.
11. Allard J, Carthey J, Cope J, et al. Medication errors: causes, prevention and reduction. Br J Haematol. 2002;116(2):255-265.
12. Neuss MN, Polovich M, McNiff K, et al. 2013 updated American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards including standards for the safe administration and management of oral chemotherapy. J Oncol Pract. 2013;9(suppl 2):5s-13s.
13. Jeon J, Taneva S, Kukreti V, et al. Toward successful migration to computerized physician order entry for chemotherapy. Curr Oncol. 2014;21(2):e221-e228.
14. Collins C, Elsaid KA. Using an enhanced oral chemotherapy computerized provider order entry system to reduce prescribing errors and improve safety. Int J Qual Health Care. 2011:23(1):36-43.
15. Weingart SN, Flug J, Brouillard D, et al. Oral chemotherapy safety practices at US cancer centres: questionnaire survey. BMJ. 2007;334(7590):407.

CASE STUDY:
Fatal ChemotherapyInterpretation Error 
Data indicate that 10% of preventable errors are related to a medication event.¹ The majority of adverse events occur during the prescribing phase of the medication-use process.² Paper-based chemotherapy prescribing systems can lead to transcription errors, as pharmacy and nursing are required to re-enter pertinent patient information into separate systems to document dispensing and drug medication administration.³ This approach can result in unclear or illegible orders, and prevents standardized documentation, both of which have been implicated in fatal medication errors.³

In 1995, Betsy Lehman died of a cyclophosphamide overdose caused by an interpretation error. The dose was written as “4 g/m² days 1-4.” The physician’s intent was that 4 g be administered over a 4-day period; however, the order was interpreted as 4 g/m² each day for 4 days. This error went undetected by multiple health care professionals, including senior attending physicians and pharmacists, and reached the patient. The lack of dose limits, dose checking, and help calculating complex dosing contributed to this unfortunate event.⁴

Because paper medication administration records tend to be encounter-based, they do not provide a longitudinal view of drug administration events across multiple patient encounters.³ Furthermore, a paper ordering system does not lend itself to the sharing of information among multiple, simultaneous users who may need to review contents at the same time. Also, paper records can be lost. 

Sidebar References

1. Bates DW, Leape LL, Cullen DJ, et al. Effect of computerized physician order entry and a team intervention on prevention of serious medication errors. JAMA. 1998;280(15):1311-1316.
2. Elsaid K, Truong T, Monckeberg M, et al. Impact of electronic chemotherapy order forms on prescribing errors at an urban medical center: results from an interrupted time-series analysis. Int J Qual Health Care. 2013;25(6):656–663.
3. Levy MA, Giuse DA, Eck C, et al. Integrated information systems for electronic chemotherapy medication administration. J Oncol Pract. 2011;7(4):226-230.
4. Cohen MR. Preventing medication errors in cancer chemotherapy. In: Cohen MR, ed. Medication Errors. 2^nd ed. Washington, DC: APhA; 2007:445-468.