Utilization of Collaborative Practice Agreements between Physicians and Pharmacists as a Mechanism to Increase Capacity to Care for Hematopoietic Stem Cell Transplant Recipients

Abstract

Survival following hematopoietic stem cell transplantation (HSCT) has improved and the number of allogeneic HSCTs performed annually in the United States is expected to reach 10,000 by 2015. The National Marrow Donor Program created the System Capacity Initiative to formulate mechanisms to care for the growing number of HSCT recipients. One proposed method to increase capacity is utilization of pharmacists to manage drug therapy via collaborative practice agreements (CPAs). Pharmacists have managed drug therapy in oncology patients with CPAs for decades; however, there are limited HSCT centers that employ this practice. Engaging in collaborative practice and billing agreements with credentialed pharmacists to manage therapeutic drug monitoring, chronic medical conditions and supportive care in HSCT recipients may be cost-effective and enable physicians to spend more time on new or more complex patients. The goal of this paper is to provide a framework for implementation of a CPA and address how it may improve HSCT program capacity.

Introduction

Over 20,000 hematopoietic stem cell transplants (HSCT) are performed in the United States (U.S.) each year.¹ The number of HSCT procedures are expected to rise as a result of increased utilization because of increased diversity and availability of graft sources, improved supportive care, more frequent use of reduced intensity regimens, and expanding indications for HSCT.² Current projections forecast the number of allogeneic HSCTs performed by 2015 will double compared with 2010.^2,3 Additionally, advances in transplantation techniques and supportive care practices have improved long-term survival following HSCT.⁴ Health care providers are exploring ways to expand the capacity to care for the increasing number of HSCT recipients. Pharmacists are key contributors to HSCT recipient care and are routinely involved in therapeutic drug monitoring, managing adverse drug reactions, addressing drug interactions, providing supportive care management and conducting patient education. Other processes pharmacists may facilitate to improve efficiency and HSCT patient capacity include responses to prescription insurance prior authorization requests, compliance with Risk Evaluation and Mitigation Strategies (REMS) programs and medication requests from patient assistance programs.

Drug therapy is one of the foundations of health care delivery. Effective management of complex drug therapy regimens and reduction in medication errors is essential. According to the Institute of Medicine (IOM), medication errors harm approximately 1.5 million patients in the U.S. each year, resulting in over 3 billion dollars in medical costs.⁵ A multidisciplinary team approach that includes pharmacists in the oncology setting has been shown to significantly reduce medication errors.^5,6 The use of a collaborative practice agreement (CPA) is one avenue to formalize clinical pharmacy practice as part of the multidisciplinary team. A CPA is formal partnership between a pharmacist(s) and physician(s), which permits a pharmacist(s) to manage a patients’ medication therapy.^7–10 A CPA may increase capacity to care for HSCT recipients, as this allows pharmacists to manage medication therapy once a physician has established a diagnosis.¹¹ The first published description of a formalized collaborative practice between physicians and pharmacists was within the Indian Health Service in the early 1970’s.^12,13 Pharmacists have utilized CPAs successfully in oncology for several decades to manage supportive therapies such as antiemetics and colony stimulating factors, as well as complications of malignancies and their treatment, including anemia, mucositis, diarrhea, constipation, and pain (Table 1).^6,14–20 Pharmacists can help to alleviate some of the burden created by the demand for physicians to care for more patients by engaging in CPAs and serving as “physician extenders” via medication therapy management (MTM) visits.⁶ MTM is a distinct service to optimize therapeutic drug outcomes for individual patients that does not require the development of formal CPAs between individual pharmacist(s) and physician(s).¹⁰

Table 1.

Collaborative Practice Agreements between Pharmacists and Physicians in Hematology/Oncology

Study	Setting	Measures	Outcomes	Impact
Chung C, et al 201119	Oncology program in community hospital	Review chemotherapy orders before/after implementation of interdisciplinary program Dosing errors Schedule errors	Cost savings (dose rounding protocol) $120,000/year 45% reduction (p< 0.0625) in chemotherapy-related errors	Positive Stronger relationships between disciplines and enhanced communication
Valgus J, et al 20116	Adult outpatient oncology clinics at university hospital	Management of supportive care by pharmacist/nurse team Education of cancer patients Improvement in efficiency of infusion center	Development of Supportive Care Consultation Service (SCCS) led to increase in patient encounters from 43% pre-implementation to 77% post-implementation Pharmacist made 186 interventions Chemotherapy counseling service led to > 900 billable patient education sessions over 18 mo 871 patient counseling sessions Developed rapid infusion protocol for Rituxan	Positive Improved supportive care management Chemotherapy unit more efficient Standardized patient education for patients receiving new chemotherapy regimens
Shah S, et al. 200618	Hematology/oncolo gy outpatient clinic at Veterans Health Administration clinic	Documentation of pharmacist driven: supportive care provided, drug-specific interventions, number of prescriptions written between 11/1/2002 to 10/31/2003 Number of patient visits	423 patient visits 342 supportive care issues addressed 308 drug specific interventions 445 prescriptions written	Positive Increased exposure of pharmacists to patients and other health care providers
Bernstein B, et al 199914	Community hospital- oncology service	Pharmacy-based CSF protocol which allowed pharmacist to stop CSF when ANC > 1500 cells/mm3 × 2 days after neutrophil nadir	CSF discontinued by a pharmacist 32% of the time Cost savings of $22,416 for CSF during first 6 mo of protocol initiation No effect on clinical efficacy	Positive
Horne A, et al 199717	Outpatient oncology clinic	Protocol for pharmacist management of adjuvant medications	Patient satisfaction survey with 51% response rate indicated patients rated their satisfaction over 90% for pharmacist performance counseling, knowledge/professionalism, and outpatient chemotherapy time	Positive
Martin JK, et al 198815	Ambulatory care ncology clinic	Pharmacy management/ prescribing of antiemetics	More than 1200 patients managed (95% of patients in clinic) 82% reported no emesis at 24 hour follow-up call	Positive

ANC indicates absolute neutrophil count; mo, months; CSF, colony stimulating factor.

One-third of allogeneic HSCT recipients and two-thirds of autologous HSCT recipients are over the age of 50.¹ Given their increasing age, HSCT recipients require management of not only their post-transplant medications but also those indicated for pre-existing conditions. Allogeneic HSCT recipients often take more than fifteen medications, including immunosuppressant, antimicrobial, anticoagulant, antihypertensive, and hypoglycemic medications.²¹ Numerous drug interactions must be managed and medication dose adjustments are often required to ensure the avoidance of drug misadventures in this population. The complexities of the HSCT recipient makes the pharmacist uniquely suited to support other practitioners to optimize patients’ medication therapy. The goal of this paper is to provide a framework for determining how to create and implement a formalized CPA and how it may improve HSCT center capacity and patient care.

CPA Definition

A CPA involves a signed contract between a pharmacist(s) and physician(s) permitting a pharmacist(s), in collaboration with the prescriber(s), to select and modify medication therapy indicated within that specified contract.^7–9 A pharmacist may perform some or all of the following activities under a CPA: “patient assessment; initiate, adjust or discontinue drug therapy; order, interpret and monitor laboratory tests; formulate clinical assessments and develop therapeutic plans; provide care coordination for wellness and prevention of disease; and conduct essential patient education”.⁹ Pharmacists can also facilitate research if they are listed as an investigator on the protocol by utilizing a CPA to order study-related medications and laboratory tests.

At the present time, 43 states have specific regulatory authority for pharmacist–physician collaboration; six states do not (Alabama, Delaware, Illinois, Kansas, Oklahoma, and South Carolina), and one is pending legislation (Missouri). Maine limits CPAs to emergency contraception only.²² The Centers for Medicare & Medicaid Services (CMS) recognized pharmacists for the first time as members of the medical staff in the hospital setting on May 16, 2012.²³ This landmark ruling allows payment for services when qualified pharmacists perform all functions within their scope of practice as permitted by state law, thus allowing reimbursement for pharmacists to manage drug therapy within a CPA. Some state laws allow practitioners to establish CPAs in all practice environments, while others restrict CPA utilization within an institution. Within institutions, utilization of a CPA may vary among services and specialties. Notably, each state has different regulations dictating the roles and responsibilities in which a pharmacist may engage. For example, some states may allow initiation of medication therapy (independent prescribing) and others may only allow modification of existing drug therapy (dependent prescribing).²⁴ An organization must comply with the Pharmacy Practice Act of the state in which it resides when developing a CPA; individual states may also include educational prerequisites, allowable drug classes, quality assurance, and documentation requirements in their regulations that govern use of CPAs.

Types of CPAs

CPAs may differ between institutions in the degree of prescribing authority, minimum education and training requirements, and documentation required. Most CPAs are reviewed for renewal on an annual or biennial basis. Selected examples of active CPAs within HSCT and some of the differences between the current models are highlighted in Table 2.

Table 2.

Examples of Current Collaborative Practice Agreements in Stem Cell Transplantation

Institution and Type of CPA	Primary Sponsors/Stakeholders	Requirements	Activities	Drugs/Diseases	Billing Structure	Other information
Duke University Medical Center (Durham, NC)	Facility [supervising MD(s)] State (NC BOP) Federal	CPP designation from NC BOP & Medicine (based on education and training/board certification) DEA registration if prescribing controlled substances	Medication Management	Most AHFS drug classes included	N/A	Supervising or covering MD(s) reviews and signs off on all patient encounters CPP meets with supervising MD(s) weekly to review patient cases
			Initiation and adjustment of therapeutic and supportive care medications	NOT authorized to order
			Labs/Diagnostics	Schedule I controlled agents Chemotherapy Radiation therapy or radiopharmaceuticals
Clinical Pharmacist Practitioner (CPP)			All lab tests needed for TDM and pertaining to diagnosis Certain medical devices
			Documentation
Inpatient AND Outpatient			All activities documented in medical record within 24 hours
University of North Carolina, Chapel Hill (Chapel Hill, NC)	Facility (supervising MD(s) and Pharmacy & Therapeutics Committee) State (NC BOP) Federal	CPP designation from NC BOP & Medicine (based on education and training/board certification) DEA registration if prescribing controlled substances	Medication Management	Most AHFS drug classes included	Facility fee billing	Supervising or covering MD(s) reviews and signs off on all patient encounters
			Initiation and adjustment of therapeutic and supportive care medications	Commonly managed conditions include: Anticoagulation Diabetes Immunosuppression Pain Vaccinations
			Labs/Diagnostics
Clinical Pharmacist Practitioner (CPP)			Laboratory Tests relevant to care and monitoring
			Documentation	NOT authorized to order Schedule I controlled agents Chemotherapy Radiation therapy or radiopharmaceuticals
Outpatient Only			All activities documented in medical record
M.D.Anderson Cancer Center (Houston, TX)	State (TX BOP) Facility [MDACC ECMS, Division of Pharmacy, supervising MD(s)]	Clinical Pharmacy Specialist Completion of ASHP-accredited PGY1 and/or PGY2 residency Each person goes through a credentialing process	Medication Management	Most AHFS drug classes included	N/A	Re-credentialing is done every year
			May sign medication orders to order, adjust or discontinue medications.	NOT authorized to order Schedule I or 2 controlled agents Chemotherapy Radiation therapy or radiopharmaceuticals
			May call in outpatient prescriptions as designated agent of the physician
			Labs/Diagnostics
DTM Protocol			Order diagnostic labs/test pertinent to drug therapy
Inpatient AND Outpatients filling prescriptions at M.D.Anderson Cancer Center			Documentation
			All orders documented in the medical record
Thomas Jefferson (Philadelphia, PA)	Facility [supervising MD(s), Office of Medical Staff Affairs] State (PA BOP)	Credentialing by facility with clinical privileges Pharmacist must carry liability insurance at a minimum of $1million per occurrence	Medication Management	Most AHFS drug classes included	N/A	Administration of certain drugs or vaccines may be permitted, but requires prior authorization by PA BOP MD signs off on all orders within 24 hours
			Adjust medication doses, frequencies, or routes
			Labs/Diagnostics
DTM Protocol			Order laboratory or other diagnostic tests pertinent to TDM
			Documentation
			All activities documented in the medical record within 24 hours
The Hospital for Sick Children (Ontario, Canada)	Facility [Medical Directives Committee, Medical Director, Professional director, responsible MD(s)]	Member of Ontario College of Pharmacists Pharmacy provider for BMT patients Acknowledgement from Medical & Pharmacy Director of pharmacist’s skills Institutional TDM certification	Medication Management	Specific drugs/drug classes included: Antimicrobials Anticonvulsants Immunosuppressants Digoxin Lithium Methotrexate Salicylate Theophylline Acetaminophen Proton pump inhibitors, ranitidine Octreotide	N/A
			Dose adjustment of medications requiring TDM, including hepatic and renal adjustment
			Labs/Diagnostics
Medical Directive			Order and interpret laboratory tests for TDM
Inpatient only			Documentation
			All activities documented in the medical record the same day
Veterans Affairs Medical Center	Facility [pharmacy, supervising MD(s), Service Chief, Professional Standards Board] State* Federal VHA (Directive 2009–014)	Pharm.D..or M.S. from ACPE-accredited SOP Completion of ASHP-accredited residency Specialty BPS certified or equivalent experience	Medication Management	Most AHFS drug classes included Not authorized to initiate controlled substances, but may renew agents already in use (if included in Scope of Practice)	N/A	Supervising MD(s) periodically assesses pharmacist’s care Various non-routine duties may be approved if qualified, such as phlebotomy or vaccine administration
			Initiate, adjust, or discontinue medications Perform limited physical assessment for TDM
			Labs/Diagnostics
Clinical Pharmacy Specialist Scope of Practice Inpatient AND Outpatient			Order and interpret results of non-invasive lab tests
			Documentation
			All activities documented in medical record (preferably within 24 hours)

ACPE indicates Accreditation Council for Pharmacy Education; AHFS, American Hospital Formulary Service; ASHP,American Society of Health-System Pharmacists; BMT, bone marrow transplantation; BOP, Board of Pharmacy; BPS, Board of Pharmaceutical Sciences; CPA, collaborative practice agreement; CPP, clinical pharmacist practitioner; DCT, Department of Cellular Therapy; DEA, Drug Enforcement Agency; DTM, drug therapy management; ECMS, Executive Committee Medical Staff; ICD-9, International Classification of Diseases, Ninth Edition; MD, medical doctor; MDACC, M.D. Anderson Cancer Center; MS, Master of Science; NC, North Carolina; N/A, not applicable; PGY, post-graduate year; Pharm.D., Doctor of Pharmacy; TDM, therapeutic drug monitoring; TX, Texas; VHA, Veteran’s Health Administration.

^*State of licensure for those who prescribe controlled substance

The Veterans Health Administration and the U.S. Department of Defense (DoD) have the most comprehensive CPAs for pharmacists.²⁵ Pharmacists with clinical privileges who practice in Veterans Affairs Medical Centers (VAMCs) and the DoD are model representatives for clinical pharmacy and have pioneered the progression and innovation of the pharmacy profession. Qualified pharmacists at VAMCs are designated as Clinical Pharmacy Specialists (CPS) and usually have prescriptive authority within their scope of practice. A CPS at the VAMC is defined as: 1) a Master or Doctor of Pharmacy who has completed a residency accredited by the American Society of Health-System Pharmacists (ASHP) and is board certified through the Board of Pharmaceutical Specialties (BPS) or 2) a pharmacist who has equivalent experience. The scope of practice for the CPS is approved by the Medical Executive Committee or similar, Chief of Staff and Chief of Pharmacy. The supervising physician authorizes the CPS to prescribe and monitor drug therapy within specific disciplines including, but not limited to; diabetes, hypertension, infectious diseases and oncology. Routine CPS duties under a CPA at the VAMC or DoD often include the following: responding to formal written consultations for pharmacotherapy and pharmacokinetics, taking medication histories, ordering and interpreting laboratory tests, and writing prescriptions for patients with chronic illnesses or for supportive care.

Some of the most unique CPA models include those in New Mexico and North Carolina. New Mexico passed the Pharmacist Prescriptive Authority Act in 1993, allowing qualified pharmacists, designated as “pharmacist clinicians” by the Board, to enter into a CPA with physicians.²⁶ Pharmacist clinicians complete additional training in diagnosis and physical assessment and may then register for their own Drug Enforcement Administration (DEA) number and apply for prescriptive authority under a supervising physician.²⁷ In North Carolina, the Clinical Pharmacist Practitioner (CPP) Act became effective in 2000, allowing qualified pharmacists to enter into CPAs with a supervising physician(s).²⁸ Applications to become a CPP are reviewed and approved by both the North Carolina State Boards of Pharmacy and Medicine. The CPP manages a patient’s drug therapy once the referring physician has established a diagnosis, treatment plan, monitoring parameters, and duration of therapy by way of protocols developed at the treating facility. Any prescriptions written by the CPP are in accordance with CPP regulations and are provided for review by the supervising physician(s). CPPs are also permitted to order laboratory tests needed to appropriately manage a patient’s drug therapy.

Benefits of a CPA

CPAs have been implemented for several disease states including diabetes mellitus, anticoagulation, hyperlipidemia, parenteral nutrition, heart failure, hypertension, smoking cessation, immunization, asthma, and infectious diseases and have generally resulted in positive patient outcomes including improved health status and decreased preventable drug-related problems.²² Randomized controlled trials involving pharmacist management via a CPA demonstrate positive outcomes, including improved asthma control²⁹, higher proportion of patients achieving cholesterol goals^30,31, better blood pressure control^32,33, improved glycosylated hemoglobin (HbA1c),^34,35 and improved International Normalized Ratio (INR) control and reduced bleeding rates in patients taking warfarin.^27,36

CPAs between pharmacists and physicians have also been established in the oncology setting. One such example is at the University of North Carolina at Chapel Hill where a clinical pharmacy service was implemented in the institution’s outpatient hematology/oncology clinic.^6,37 The pharmacist involved in the pilot program completed an ASHP-accredited oncology pharmacy residency and was a BPS Board Certified Oncology Pharmacist and a CPP approved by the North Carolina State Boards of Pharmacy and Medicine. The CPP identified three initial patient-related goals: 1) manage patient supportive care; 2) develop and provide standardized education to all patients receiving complex chemotherapy regimens; and 3) improve efficiency in the outpatient oncology infusion clinic by developing and initiating a rituximab (Rituxan®, Genentech, Inc.) rapid infusion protocol..⁶ The CPP conducted 63 educational interviews over a 7-month period to provide standardized verbal and written patient education about the patients’ chemotherapy regimen, anticipated adverse effects, and their management. The CPP was given the authority to prescribe under physician supervision using agreed upon protocols, leading to improvements in symptom scores on a 5-point Likert scale for pain, nausea and constipation.^37,38 Over fifty percent of the pharmacist interventions involved antiemetic therapy; other common interventions included resolving chemotherapy order errors and adjusting pain and bowel regimens using pre-defined algorithms. Initial analysis of the first 50 patients treated under the pharmacist-led rituximab rapid infusion protocol identified a similar rate of infusion reactions compared with patients treated per the manufacturer’s recommendations and an average time saving of 91 minutes per patient with the shorter infusion. This initiative improved efficiency in the chemotherapy infusion unit and was estimated to allow for an additional two to three patient visits per week without additional resource expenditures. This project demonstrated that the integration of a CPP into the hematology/oncology clinic under a CPA improved the supportive care management of cancer patients, increased the efficiency of the chemotherapy infusion unit, and standardized education to patients receiving complex chemotherapy regimens.⁶

There are currently no published reports documenting utilization or outcomes of CPAs between a pharmacist and physician in the HSCT population and only a small number of HSCT centers have formal CPAs in place. The complexity of drug therapy regimens in HSCT recipients makes utilization of CPAs potentially beneficial to both patients and physicians in a number of ways. Pharmacist-physician collaboration via CPAs could free up physician and advanced practice professional time to see more patients and focus on more complicated diagnostic issues, and in turn meet the demand of the increasing number of allogeneic HSCTs in the U.S. Pharmacists also play an integral role in necessary patient education to improve medication adherence and understanding of medications.^39–41 Some of the HSCT-specific therapy decisions pharmacists could be involved in include: initiating, monitoring and modifying medications that require therapeutic drug monitoring, adjusting therapy for supportive care needs, managing drug interactions; monitoring for and treating transplant regimen-related toxicities and chronic conditions (e.g. hypertension, diabetes, hyperlipidemia); ordering and interpreting laboratory tests pertinent to drug therapy; creating, implementing and guiding standardized treatment algorithms; and providing patient education and follow-up.

Processes for Implementing a CPA

Conduct a Needs Assessment

The initial step in implementing a CPA is to conduct a needs assessment at your institution to determine what stakeholders identify as areas in need of improvement both in the current model and in the future with anticipated increased numbers of allogeneic HSCT recipients. Physicians, nurses, advanced practice professionals, pharmacists, patients, and institution administration should be queried to determine how to optimize pharmacy services to enhance patient care. Providers may identify patient care management aspects that are labor intensive such as therapeutic drug monitoring for calcineurin inhibitors. MTM of comorbidities in the HSCT setting including dyslipidemia, hypertension and diabetes may also be beneficial where organ dysfunction and drug interactions make pharmacotherapy more complex. Providers may identify resolving insurance coverage gaps as a priority. Patients may express concerns with cost of medications and a desire to minimize the complexity of the regimen. Explaining possible benefits of a CPA and how it works are essential to the agreement’s success.

Evaluate staffing constraints

A pharmacist may already practice in an environment where implementing a CPA will not require additional funding for a pharmacist position. A CPA may actually improve efficiency by allowing for medication adjustments without provider contact. In other settings, additional pharmacy personnel may be needed to manage patients via a CPA.

Identify Training Requirements

The organization should determine which pharmacists will practice within CPAs and what combination of credentials, training and experience is necessary for those pharmacists.^42,43 Some requirements to consider for pharmacists participating in a CPA in HSCT, in addition to those required by the state the pharmacist practices in, may include: completion of an ASHP-accredited oncology pharmacy residency, BPS Board Certification in Oncology Pharmacy, and completion of an institution-specific training program. Some CPAs allow pharmacy residents to participate under the supervision of a preceptor pharmacist or a physician; institutions that train pharmacy residents must address how they will be utilized.

Develop the CPA

Pharmacists and physicians should collaborate to develop a CPA that benefits HSCT recipients. Providers may determine that a CPA with a defined protocol is most helpful. This may include specific algorithms for management of selected chronic medical conditions such as osteoporosis, diabetes, dyslipidemia or hypertension based on clearly defined decision criteria, or management of certain medications such as immunosuppressive therapy, warfarin and/or vaccines. Typical sections included in a CPA are described in Table 3.

Table 3.

Representative Sections of a Collaborative Practice Agreement

Program Overview Purpose Patient Inclusion Criteria Responsibilities Monitoring and Treatment Guidelines CPA Operating Instructions Training Requirements Quality Improvement

Adapted with permission from Practice Advisory on Collaborative Drug Therapy Management by Academy of Managed Care Pharmacy¹⁰

Alternatively, a CPA may be more appropriate wherein qualified pharmacists working within the context of a defined protocol are permitted to assume professional responsibility for performing patient assessments; ordering drug therapy-related laboratory tests; administering drugs; and selecting, initiating, monitoring, continuing, and adjusting drug regimens.⁹ Either type of agreement should be mutually agreed upon by the collaborating physicians and pharmacists and reviewed by an appropriate body responsible for quality assurance within the clinician’s practice setting.

A CPA should clearly define the patient population, scope of patient care, setting, and time frame to which the CPA will apply. Patients may be seen either through referral to the pharmacy service by another health care provider or by defined inclusion characteristics such as all HSCT recipients or those patients that meet specific criteria. The CPA may allow for only therapeutic drug monitoring and adjustment of calcineurin inhibitors or management of chronic medical conditions, or it may be more generalized to cover most HSCT-related medication needs. The CPA should define the applicable patient setting (hospital, hospital–based outpatients, clinic-based outpatients) and the time frame covered (e.g. only prior to 100 days post-HSCT or as long as the patient remains on immunosuppression). Ambulatory patients who might benefit most from pharmacist monitoring include 1) patients on five or more medications, 2) patients receiving at least twelve medication doses per day, 3) patients whose medication regimen changes more than four times in the past 12 months, 4) poor medication adherence or 5) patients on medications that require therapeutic drug monitoring.⁴⁴ Finally, the CPA should identify criteria for patient discharge from the pharmacist’s care (e.g. patient no longer on immunosuppression, patient is past a landmark time point, patient no longer wishes to receive care).

The CPA should be reviewed and signed by all pharmacists and physicians who will practice under the agreement. Other departments or governing bodies often need to review and approve the CPA and are institution-specific, such as the organization’s pharmacy and therapeutics committee, credentialing committee, legal department and/or hospital administration.

Implement the CPA

Key elements of a successful CPA are described in Table 4. The collaborative practice can begin once the CPA has been developed and approved; however, a staffing model for patient care should first be determined to allow for a smooth transition and to ensure an efficient practice. The pharmacist should establish a regular location for patient encounters, the frequency of patient visits and plans for follow up (in person or via telephone or internet). A method of scheduling patients should be implemented; pharmacists can often employ the same system used by other providers. The duration of patient visits needs to be established, such as an initial visit of one hour followed by subsequent visits of 15 to 30 minutes.

Table 4.

Key Elements for an Effective Collaborative Practice Agreement

Professional relationship	An environment whereby one or more pharmacist(s) and one or more physician(s) have professional relationships sufficient to allow pharmacists under a written and signed agreement to perform certain patient care functions under pre-specified conditions
Access	Access to patients and pertinent information from their medical record. Access to pertinent patient laboratory tests and results
Competency	Pharmacist knowledge, skills and ability to perform authorized functions
Communication	Documentation and communication of pertinent information in the patient’s medical record
Accountability	Accountability for quality measures
Reimbursement	Ability to be reimbursed for drug therapy management activities
Resources	Commitment of the time and resources necessary to achieve stated goals and objectives

Adapted with permission from Practice Advisory on Collaborative Drug Therapy Management by Academy of Managed Care Pharmacy¹⁰

The pharmacist should document every patient encounter in the medical record including a complete medication list, medication adherence, pertinent laboratory values, effectiveness and tolerability of therapy, medication adjustments made and treatment goals. Additional documentation is required if the pharmacist bills for services via MTM. The documentation requirements for MTM are a time-consuming aspect of billing for cognitive pharmacy services, with one publication describing a median of 18 minutes (range 5–90) for documentation per visit. ²⁰

Pharmacists and physicians should address potential problems with implementation prior to initiating the CPA. One possible barrier is the Social Security Act, where CMS defines physicians, nurse practitioners and physician assistants as practitioners whose services are eligible for Medicare Part B reimbursement, but not pharmacists; this means that prescription drug claims billed under Medicare Part B for prescriptions written by a pharmacist under a CPA and filled at a retail pharmacy will not be paid for by Medicare. This generally only applies to selected oral chemotherapy agents and immunosuppressants. Medicare Part D prescription drug sponsors must recognize a physicians’ authority to delegate prescribing where authorized by state law.⁴⁵ There have been previous unsuccessful attempts to amend the Social Security Act to include pharmacists as eligible practitioners in 2004, 2008 and 2010.⁴² Other potential problems include requests for pharmacists to provide services outside of the scope of their CPA (e.g. obtain prior authorization from insurance companies for prescriptions written by other providers or requesting medication from patient assistance programs). Clear definitions of who is responsible for which activities are necessary to ensure continuity of care, avoidance of medication errors and duplication of work. A third possible barrier to implementation is physicians in some settings may have variable levels of confidence in delegating prescribing authority to pharmacists via a CPA.⁴⁶

Measuring Outcomes of CPAs

Once a CPA is implemented, outcomes should be measured to determine the pharmacist(s)’ impact. Outcome measures for clinical pharmacy services should be comprehensive, accountable, scientifically sound, feasible and usable.⁴⁷ Data supporting pharmacist-directed outcomes in HSCT have not been reported; however, there are publications in oncology that describe the development and implementation of pharmacist-inclusive services in the areas of supportive care, symptom management, and disease state management. ^{6,14,15,17–20,39,48} The outcomes reported in these studies vary widely, from raw data such as number of patient visits and prescriptions written, to measured endpoints such as cost savings and patient satisfaction. A review of all of the above practice areas and measures supports opportunities for pharmacists in the HSCT field to capture outcomes data from traditional acute and ambulatory care practice settings and collaborative practice-based settings. Outcomes are usually defined as clinical, economic or humanistic. Those potential outcomes that can be measured as a basis for pharmacist impact in HSCT are described in detail in this section.

Clinical Outcomes

The gold standard of clinical outcomes data is improvement in the clinical course of patients; however, it is also the most challenging to capture and relate back to a single intervention, such as a pharmacist’s involvement in care. Changes in survival, duration of hospitalization, or graft-versus-host disease based on a single discipline’s intervention are difficult to measure in HSCT recipients because of the complex and multidisciplinary nature of HSCT recipient care.

Surrogate outcomes

Surrogate markers have been previously documented to impact patient outcomes and may be used by the pharmacist to measure impact of services. These surrogates include re-hospitalization rates, maintenance of calcineurin inhibitor plasma levels within a pre-defined range, vaccination status post-HSCT, blood pressure or lipid control, decrease in HbA1c in steroid-induced diabetes, and INR maintenance in patients taking warfarin.^49–53 These measures are known to impact the clinical course and outcomes of HSCT recipients, and are outcomes that may be positively impacted by pharmacist management.

Medication Adherence

Improved patient adherence to medication regimens and post-transplant care is critical to achieving positive clinical outcomes. Studies of patients with HIV, diabetes and cancer have demonstrated that pharmacists play an integral role in patient adherence and understanding of their complex medication regimens.^39,54,55 HSCT recipients, particularly those receiving allogeneic HSCT, frequently take multiple concurrent medications and the potential for clinically significant drug interactions is high. Adherence to a proper medication regimen and schedule is vital to attain positive outcomes in HSCT recipients. Adherence to medications can be measured by conducting patient interviews, tracking medication logs and counting pills. These simple tools can display the impact of pharmacist education and counseling on a patient’s understanding and adherence with his/her medications.

Provider compliance with guidelines and algorithms

Pharmacists have been involved in algorithm development for oncology-associated conditions including anemia, pain, use of colony stimulating factors and chemotherapy-induced nausea and vomiting.^{6,14–17,56–58} HSCT pharmacists often participate in development of critical pathways and algorithms for standardized use of medication therapy, including those employed for HSCT center accreditation through the Foundation for the Accreditation of Cellular Therapy. Noncompliance with treatment guidelines and algorithms can translate into adverse patient outcomes.^59,60 Additionally, many HSCT programs are staffed by a variety of disciplines with different backgrounds and training including medical residents and fellows, nurses, and advanced practice professionals. Creation of critical pathways and algorithms in HSCT and evaluation of the impact and adherence to those algorithms and guidelines can help maintain consistency and uniformity in patient care.

Economic outcomes

Some chronic diseases require close monitoring and frequent medication dose adjustments; however, managing these patients is not a cost-efficient activity for physicians. Engaging in CPAs with credentialed pharmacists may be cost-effective and enable physicians and advance practice professionals to spend more time on new or more complex patients.⁴² If pharmacist-based management of certain chronic diseases and post-HSCT complications can save providers time and allow them to provide higher-value clinical services to a greater number of patients, this can translate into not only cost savings but possibly increased revenue.

Pharmacists can also reduce costs to the institution by selecting the most cost-effective therapy when several equally effective options are available. HSCT programs often have the most costly drug budgets and highest acuity of care within an institution. Pharmacist involvement in cost containment resulting from streamlined use of high-cost medications, implementation of drug-use algorithms, and formulary management are relatively easy outcomes to measure.

Pharmacists can also bill for services in hospital-based clinics using Current Procedural Terminology Evaluation and Management (CPT E&M) Codes 99211-99215, a method that can help to offset some of the expense of having a pharmacist care for patients via CPAs.⁶¹ A pharmacist can bill “incident to” a physician in this practice setting using facility fee-only billing (no professional fee for the pharmacist services). In one solid organ transplant setting, the utilization of a pharmacist billing via facility fees increased billing by approximately one hundred dollars per patient visit.⁶³ Pharmacists can also bill “incident to” a physician in clinic-based outpatient settings; however, this is at the lowest level of reimbursement.⁶⁴ Alternatively, pharmacists can bill Medicare part D for clinic-based outpatients for cognitive services of MTM via CPT codes 99605, 99606 and 99607.²⁰ If a patient has health insurance coverage other than Medicare Part D and is a candidate for MTM services, the payer will need to be contacted to determine if MTM services are covered, what codes to use, and how to submit the claim. This may be a challenging task, as HSCT centers have a high number of patient referrals and encounter multiple insurance plans. Each payer typically has its own criteria for patient eligibility for MTM services and pharmacist requirements. Reimbursement rates range from 47% to 79% depending on the insurance provider in one publication of pharmacist-provided MTM in oncology patients.²⁰ Reimbursement through MTM CPT codes alone generally will not support the entire salary for a pharmacist that manages outpatient HSCT recipients with chronic conditions and high acuity. Accordingly, HSCT pharmacists should measure and publish the value of the services they provide to support future increases in payment for cognitive services.

Humanistic Outcomes

Patient satisfaction is a valuable and influential outcome. Satisfaction with care leads to increased treatment referrals and improved treatment adherence.^63–65 One study has demonstrated that oncology pharmacists have a positive impact on patient satisfaction.⁶⁶ Pharmacists working in CPA-based HSCT clinics are in a position to see patients regularly, as most patients have frequent follow-up prior to and post-transplantation. Pharmacist-provided continuity of care from the inpatient to the outpatient setting may have a positive impact on patient satisfaction.

Pharmacists practicing in CPA-based clinics can also have a sustained and significant impact on provider satisfaction. Providers’ perceptions of specialty pharmacy services in numerous acute care and ambulatory care settings have been positive.^46,67 Satisfaction from these services was derived from the provision of novel pharmacy services as well as managing issues that can be burdensome for providers including therapeutic drug monitoring, medication reconciliation and insurance coverage issues. HSCT recipients are often prescribed medications requiring therapeutic drug monitoring, prior insurance authorization, specialty pharmacy dispensing, or compliance with REMS programs. Pharmacist management of these aspects of care may positively impact provider satisfaction.

Clinical, economic and humanistic outcomes of CPA-based pharmacy practice in HSCT can be measured using a variety of tools as described. The type and extent of such outcome measurements relies greatly on endorsement of pharmacist collaborative drug therapy management from the health care system and the transplant team. The pharmacist must appropriately gauge their resources and ability to track outcomes, as any endeavor to measure outcomes can only be successful if the correct endpoints are measured consistently and accurately.

Conclusion

There is a projected shortage of health care providers in the HSCT setting and a multidisciplinary, collaborative approach to patient care is crucial.³ Pharmacists have the knowledge base and skills to assist physicians and advanced practice professionals with drug therapy management. Most states have passed legislation or revised their state medical and pharmacy practice acts authorizing pharmacists to provide care under CPAs. Implementation of a CPA may improve the capacity to care for the expected future increase in HSCT recipients. Facilities that implement pharmacist-provider CPAs to assist in the care for HSCT recipients should document and publish their outcomes supporting this practice, which will enable others to justify adoption of this process.