Contents
Guest Commentary
Peer-Reviewed Articles
Peer-Reviewed Student Articles
The Vital Relationship Between Public Health and Pharmacy
Charles D. Sands, III, PharmD, Professor, Department of Pharmacy Practice, McWhorter School of Pharmacy, Samford University, Birmingham, AL
Key Words: Public Health, Community Pharmacy Services, Education
Public health and pharmacy have been closely associated for millennia. The public health profession associates the image of Hygeia, the Greek mythological goddess of health, with the practice of public health. Hygeia is one of the most widely recognized symbols of public health practice. Almost all representations of the goddess Hygeia show her holding a large bowl and a snake. The bowl is known as the Bowl of Hygeia and it is the universally recognized symbol for the profession of pharmacy. Health, hygiene, and pharmacy are inextricably linked.
Although pharmacists play an important role in most state public health systems, little has been done to try to maximize the community health status benefits that might accrue from of a close, coordinated relationship between the practices of pharmacy and public health. The purpose of this commentary article is to describe some of the current thinking and activities that are addressing this endeavor.
Public Health has been described by the Institute of Medicine of the National Academy of Sciences as "what we as a society do to assure the conditions in which people can be healthy."[1] Hence, Public Health is about prevention and what we can do as communities to raise the health status of our entire population by preventing disease, disability, and premature death.
Public health services have been characterized as occurring on two levels: the planning (or "macro") level and the implementation ("micro" or "provider") level. While many pharmacy enabled prevention activities have been described that can be implemented at the micro level by community pharmacists, evidence suggests that a small minority of community pharmacies are involved in preventive services delivery.
As an example, a recent study by Jeanine Mount[2] of the University of Wisconsin and others presented at the 2006 meeting of the American Association of Colleges of Pharmacy, surveyed nearly 1700 community pharmacies and found that only 17.9 percent of the respondents were involved in pharmacy based immunization delivery - one of the most common and fundamental preventive services.
The importance of expanding community pharmacy based immunization services substantially over the low levels found in the Mount study, goes beyond traditional public health concerns. Today in public health practice, there are significant concerns about our capacity to respond to a pandemic disease outbreak or to a widespread outbreak of disease as a result of terrorism. Many of the scenarios about how society must respond include the delivery of vaccinations. The provision of vaccinations to thousands of people over a large geographic area in a very short period of time is a complex undertaking requiring many well trained individuals. The state health department in New York announced that it will propose legislation to "authorize the Commissioner of Health and local health officers to train and authorize unlicensed persons to give immunizations"[3] so that they could be called into service when widespread and rapid vaccination programs are required. How the health department would select the individuals to be trained throughout the state, how they would train so many people in this skill, and most importantly, how they would assure the maintenance of these vaccination skills over time is a substantial challenge. Clearly, widespread adoption of community pharmacy based vaccination services would address this issue and provide the public health capacity to respond to large scale vaccine preventable disease outbreaks.
While it is fundamental to community health status and disaster response, immunization is only one of a number of community pharmacy based preventive health services that can be enhanced by closer collaborations between public health practice and pharmacy practice. Examples include community pharmacy enabled screening programs to increase early therapeutic interventions in numerous chronic diseases states such as diabetes, hyperlipidemia, obesity and hypertension.
The Veterans Administration (VA) has been especially active in the use and evaluation of pharmacy enabled preventive interventions. In one recent study[4], the Philadelphia, Pennsylvania VA Medical Center was the setting for a prospective controlled study to determine whether pharmaceutical care provided in a pharmacist-managed hypertension clinic would result in better treatment outcomes when compared with traditional care from a primary care physician. Eighty-one percent of the patients in the pharmacy care intervention group attained their blood pressure goal of below 140/90 mm Hg at the completion of the study versus only 30% in the control group (P<0.0001).
In addition to the various pharmacy based preventive services that address specific disease states, the current epidemic of adverse drug events could be significantly impacted by more widespread delivery of medication therapy management services through community pharmacies. Congress specifically noted the importance of the availability of such a pharmacy enabled service in the statutory language of the new Medicare Part D prescription drug benefit. The language in the statute states:
A medication therapy management program described in this paragraph is a program of drug therapy management that may be furnished by a pharmacist and that is designed to assure, with respect to targeted beneficiaries described in clause (ii), that covered part D drugs under the prescription drug plan are appropriately used to optimize therapeutic outcomes through improved medication use, and to reduce the risk of adverse events, including adverse drug interactions.[5]The relationship between public health and pharmacy, at the provider or "micro" level of practice, creates direct patient specific interventions for improving community health status. However, the relationship at the "macro" level may be even more fundamental to the establishment of effective pharmacy enabled preventive services.
Macro level public health activities focus on the health status of the community as a whole and emphasize assessment, policy development, and planning and evaluation to assure needed services. Such activities include working with community representatives to diagnose and investigate community health problems; establishing community partnerships to prioritize solutions to health problems; developing policies and plans that support individual and community prevention efforts; managing, administering, and evaluating community health-promotion programs; educating the public on community health needs and public health policy issues; and conducting research on the effectiveness of public health activities and communicating the results of research efforts.[6]
Over 25 years ago, Bush and Johnson pointed out the importance of pharmacists at the macro level. They stated in part, "The lack of attention to the need for pharmacists at the macro level of the health-care system has affected the micro level as well. It is the macro level public health pharmacist (emphasis added) who can address the problem of incentives for pharmacists to perform micro level public health activities. Macro level public health pharmacists who are knowledgeable about the training and abilities of pharmacists (and who understand the health-care system, inter-professional relationships and health economics) can suggest system level changes that can provide direct and indirect incentives (money and its substitutes) to pharmacists to perform public health activities."[7]
Today, approximately 1% of all public health employees are pharmacists.[8] It is likely that the single largest group of public health pharmacists is serving at the federal level through various roles in the United States Public Health Service including substantial numbers with medical care delivery systems such as the Indian Health Service. Smaller pharmacy cohorts' function at the state and local levels of public health practice.
The primary responsibility for the delivery of public health services in the United States resides at the state level. Protection of the public's health is primarily a state function and hence the majority of all authority to take actions for public health is within the police powers of the states. The roles and responsibilities of pharmacists at the state level of the public health system are vital, not only to the effective delivery of preventive services through traditional public health agencies, but, as Bush and Johnson suggest, they are fundamental to the expansion of pharmacy enabled preventive health services within our communities. The importance of these roles for pharmacists, not only at the micro level but also at the macro level of public health practice is now being recognized by the academic pharmacy community.
New competency requirements from the Accrediting Council on Pharmacy Education are aimed at increasing both the knowledge among pharmacy students about the public health system, and the public health competencies of graduates of PharmD programs. The standards are clearly designed to improve the ability of pharmacists to function effectively at the state level of our public health system. Specifically, Standard 12 of the new Accreditation Standards and Guidelines that will become effective in July, 2007 states that the professional pharmacist competencies that must be achieved by graduates through the professional degree program curriculum are the ability to:
Promote health improvement, wellness, and disease prevention in cooperation with patients, communities, at-risk populations, and other members of an interprofessional team of health care providers. . . .Increasing the participation of pharmacists in all levels of the public health system is fundamental to achieving substantial improvement in the health status of our population as well as to achieving full preparedness to respond to any type of mass casualty event. Pharmacy education is addressing this important goal directly through changes to its self-governing processes of peer-review and accreditation. Increasing the participation of highly trained pharmacy professionals at the state level of public health practice must be one of the most important goals for the future of our public's health.In this regard, the college or school must ensure that graduates are competent to: . . .
promote the availability of effective health and disease prevention services and health policy through the ability to apply population-specific data, quality improvement strategies, informatics, and research processes to identify and solve public health problems and to help develop health policy.[9]
References
1. The Future of Public Health. Washington, D.C: National Academies Press;1988:1.
2. Mount JK, Watcharadamrongkun S, Kim M, Westrick, SC. Is Affiliation with a Pharmacy School Related to a Community Pharmacy's Public Health Involvements? Poster presentation at: Annual Meeting of the American Association of Colleges of Pharmacy; July 17, 2006; San Diego, CA.
3. Department of Health, NY State Web site. Transcript of Oral Testimony State Senate Hearing on Pandemic Flu, March 10, 2006. Available at: http://www.health.state.ny.us/ press/releases/2006/2006-03-10_pandemic_flu_novello_testimony.htm. Accessed October 30, 2006.
4. Vivian EM. Improving Blood Pressure Control in a Pharmacist-managed Hypertension Clinic. Pharmacotherapy. 2002;12:1533-1540.
5. SSA Part D. Beneficiary Protections for Qualified Prescription Drug Coverage. Sec 1860d- 4. Part c.2 A.i.
6. The Future of the Public's Health in the 21st Century. Washington, D.C: National Academies Press;2003: 97, 417.
7. Bush PJ, Johnson KW. Where is the public health pharmacist? Am J of Pharm Edu. 1979;43:249-253.
8. US Public Health Service Pharmacy Web site. Available at: http://www.hhs.gov/pharmacy/ phpharm/slideshow.html. Assessed October 15, 2006.
9. Accreditation Council for Pharmacy Education, Accreditation Standards and Guidelines for the Professional Program in Pharmacy Leading to the Doctor of Pharmacy Degree. 2006;18-19. Available at: http://www.acpe-accredit.org/ pdf/ACPE_Revised_PharmD_Standards_Adopted_Jan152006.pdf. Accessed November 10, 2006.
Pharmacogenomics in the Professional Pharmacy Curriculum: Content, Presentation and Importance
Sally A. Huston, PhD, BS Pharm, Assistant Professor, South University, School of Pharmacy, Savannah, GA
Grady S. Weston, PhD, BS Pharm, Assistant Professor, Feik School of Pharmacy, University of the Incarnate Word, San Antonio, TX
Abstract
The current study was designed to examine the types and quantities of pharmacogenomics (PG) content taught in U.S. and Canadian pharmacy schools as well as the methods of presentation used. It also assessed faculty perceptions of the adequacy and importance of PG content in their current curriculum. A four-page survey was mailed to the dean of each School of Pharmacy for distribution to the appropriate faculty member(s). The results of the study indicate that a majority (87%) of pharmacy schools included PG content in their curriculum. The role of PG in drug metabolism, drug transport and specific disease states were most frequently addressed by faculty teaching PG. The majority of faculty responders believed their current amount of PG content was inadequate but expected it to increase in the future. The scope and degree of PG coverage was highly variable with no clear consensus on courses, content or amount of coverage. In addition, definitive PG resources that might aid the teaching of PG appear to be lacking. The majority of both students and faculty in all areas of pharmacy considered knowledge in PG to be very important for their current and future practice.
Keywords. pharmacogenomics, pharmacy education, teaching methodologies, curriculum, survey
Introduction
Pharmacogenomics (PG) is the study of the genes that influence drug behavior and effects in individuals. While the genomes of any two individuals are essentially (99%) identical, there are still approximately 3 million nucleotides that differ between individuals. Most of these variations occur as single nucleotide polymorphisms (SNPs) in which one nucleotide is exchanged with another at a given position. Although seemingly minor genetic changes, these polymorphisms can have major effects on the way humans respond to drugs, disease, and toxins in the environment. Genetic polymorphisms are capable of altering drug target pathways as well as the enzymes that metabolize drugs. With completion of the Human Genome Project[1] and the advent of deoxyribonucleic acid (DNA) microarrays[2], it is now possible to rapidly analyze thousands of DNA segments from a patient for genetic variants. In recognition of the potential importance genetic variants may play in drug response, a private consortium of pharmaceutical companies (SNP Consortium)[3] have set out to map all human SNP's.
The ultimate goal of pharmacogenomics is to tailor drug therapy for an individual based on his or her genetic composition in order to maximize therapeutic effectiveness and minimize toxicity. Although still in an early stage, some of the findings from pharmacogenomic research have already begun to impact clinical practice and drug therapy. For example, genetic polymorphisms in CYP450 enzymes can significantly alter the rate at which patients metabolize a number of drugs from important classes such as antidepressants, anesthetics, antiseizure agents and anticancer drugs,[4,5] thereby markedly altering blood levels of these agents. Genetic variation in drug transporters, drug receptors and target enzymes can likewise alter the pharmacodynamic response of patients to various drugs[6]. Patient testing for specific genetic variants has been used to improve efficacy and reduce toxicity of chemotherapy[7], enhance statin therapy of hypercholesterolemia[8], and improve treatment of depression with SSRI's.[9]
As advances in pharmacogenomics increasingly influence clinical practice, pharmacists will need to become knowledgeable in various aspects of pharmacogenomics, including data interpretation, study methodologies and the application of specific genetic findings to the care of their patients. In 2001-2002, the charge of the Academic Affairs Committee of the American Association of Colleges of Pharmacy (AACP) was expanded to include consideration of the impact of the emerging knowledge of pharmacogenetics, pharmacogenomics, proteomics and bioinformatics on the future role of the pharmacist[10]. A recent study by Latif[11] reported that while most schools of pharmacy were providing some instruction in PG, it was not to the depth recommended by AACP[10]. According to their findings, the average school of pharmacy was currently addressing only about half of the AACP recommendations pertaining to specific PG content such as the genetic basis of disease and only about one third of the AACP recommendations related to ethical, social and economic factors. A second recent article by Sansgiry[12] used a detailed survey to evaluate the confidence that community pharmacists had in their knowledge surrounding the human genome project, genetic testing and pharmacogenomics. Results of the study indicated that confidence levels were low. This suggests a need to educate existing community pharmacists as well as current students about the potential impact of PG on the practice of pharmacy now and in the future. Continuing education should be enhanced in these areas.
In light of these findings and the rapid growth occurring in the field of pharmacogenomics, we decided to examine pharmacogenomics content within the PharmD curricula of U.S. and Canadian Schools of Pharmacy. Questions included: what percentage of U.S. and Canadian schools of pharmacy include PG content in their curriculum; what specific content is presented and in what courses is PG content included; how is PG content delivered and what resources are utilized in its delivery? We were also interested in assessing whether pharmacy faculty teaching in this area felt the amount of PG content currently offered in their curriculum was sufficient and if they thought the amount of content would increase in the future. Finally we asked faculty how important they believed it was for students and pharmacists practicing in various areas to have a PG knowledge base.
Methods
To collect data for the study, a 23 question survey was developed (see Appendix A). The survey was sent to the dean of each School of Pharmacy in the U.S. and Canada (100 surveys total). The survey was accompanied by a detailed cover letter that stated the objectives of the study and asked the dean to forward the survey to the appropriate faculty member(s) within their school. The first page of the survey also listed the objectives of the current study along with instructions and contact information for the authors. Anonymity was assured. A self-addressed, stamped envelope was included with each survey to facilitate its return, which was requested within one month.
The survey was divided into 3 parts. The first series of questions focused on PG content, asking which specific courses included PG content, what specific content areas were addressed, in what year of the curriculum was this content offered and how many total contact hours were allotted for PG content. Questions were also asked in this section regarding PG electives that were currently offered or planned in the future. Survey recipients were asked if they believed the current amount of PG content in their curriculum was sufficient and if they expected the amount of content to change significantly over the next few years.
The second section of the survey contained questions on PG content delivery. Respondents were asked about delivery format, whether or not they used small-group discussion or case studies, and whether or not they gave written assignments. Subsequent questions were also asked regarding specific readings, texts, journals or Web sites that were assigned or used by the students.
The third section focused on the perceived importance of PG content in the pharmacy curriculum and in pharmacy practice. Survey respondents were asked how important they felt PG knowledge was for current pharmacy students, as well as for health-system and community practitioners. Finally, the survey asked respondents whether or not they agreed with the statement that in the future, only certain specialist pharmacists would need to know the principles of pharmacogenomics. The surveys contained no identifiers and were returned anonymously.
Results
A total of 100 surveys were sent out, 46 were received before the cut-off date, yielding a response rate of 46%. Of the schools responding to the survey, 85% reported including PG content in their current curriculum (Table 1). In 95% of these schools, PG content was a required element. The majority of institutions offered between 1 and 26 teaching hours with the median content being 7 hours (mean = 10.1 hours with a S.D. ± 7.2). A single institution offered 60 hours (Table 1). The data in Table 1 shows that PG content was mainly distributed across the first 3 years of the professional curriculum with the majority of schools (68%) emphasizing this content in the second professional year. Of those schools with PG content, only 2.7% offered it during the fourth professional year. The reported number of PG elective courses also was low with only 8.5% of responding schools offering an elective related to PG.
Figure 1 lists the specific courses in which schools reported significant PG content. While PG content was found in a wide range of courses across the various schools of pharmacy, the most common courses including PG content were biochemistry, pharmacokinetics and pharmacology followed by medicinal chemistry. "Other" was the single largest category reported with 35% of schools offering PG content in a course other than the 10 listed on the survey. Some examples of "other" courses that included PG content were physiology, pharmaceutical biotechnology, molecular medicine, PG elective, drug interactions elective, biotechnology and biomedical sciences modules.
Figure 2 provides a breakdown of specific PG content areas that responding schools included in their curriculum. Six of the 9 PG content areas listed on the survey were included in the curriculum of at least 70% of the Schools of Pharmacy who included PG in their curriculum. Ninety percent of respondents included the role of pharmacogenomics in drug metabolism while 80% focused on the role of PG in drug transport. Approximately 20% of schools included other topic areas such as the impact of PG on pharmacy, the pharmacoeconomics of PG and the role of the pharmacist in PG.
As seen in Table 2, the primary method for delivery of PG content was didactic lecture. Over 90% of respondents who taught PG content supplemented their lecture with instructor handouts. Sixty-four percent of respondents used case presentations while 30% employed group discussions. Assigned reading in PG was given by 68% of respondents. Only 41% and 38% of faculty used a specific textbook or journal respectively as their primary reading source. When asked to list what specific text or journal was used for their PG course, no text or journal title appeared more than one time. Homework was assigned by 33% of respondents while 46% included some online materials to supplement their PG content.
When surveyed faculty were asked if they felt the current level of PG content in their curriculum was adequate, 60% of faculty responded that it was less than adequate, 37% felt it was adequate and none felt it was more than adequate (Table 3). Nearly 70% of respondents currently offering PG content believed the amount of content in their curriculum would increase in the future while 83% of respondents not currently offering PG content believed that it would be included in their curriculum in the future.
The last section of the survey was designed to gauge faculty opinion as to how important they believed PG knowledge is to current PharmD students and practicing community and health-systems pharmacists. As seen in Figure 3, greater than 80% of respondents believed such PG knowledge was either "very important" or "important" for both current PharmD students and health-systems pharmacists. Over 80% of respondents disagreed with the statement that "only specialist pharmacists will need to know PG."
Discussion
It appears that the vast majority (nearly 90%) of schools of pharmacy in the U.S. and Canada currently offer PG content in their curriculum. Among 95% of responding schools, PG content was a required element. Recent studies by Latif[11] and Moridani[13] reported that 78% and 60% respectively of the schools of pharmacy responding to their survey offer pharmacogenomics content. Latif's study concluded that while the majority of pharmacy schools surveyed provide some instruction in PG, many do not provide the depth recommended by AACP. Both studies surveyed U.S. schools of pharmacy, which response rates were 48% and 34% respectively. The authors believe the overall response rate for our survey (46%) was good and we would like to think it might be in part due to the perceived interest and importance of the topic in pharmacy education.
In light of the high reported rate of PG content inclusion in the curriculum, it seems that schools of pharmacy have been proactive toward including emerging PG knowledge in the pharmacy curriculum. Interestingly, more than half of respondents who offered PG content felt the amount currently offered was less than adequate. On a positive note, most of those respondents who believed the current level of PG content was inadequate or who did not currently offer PG content, believed the amount would increase in the near future, which was a finding echoed in the study by Latif[11].
Most PG content was included in P1-P3 years of the pharmacy curriculum with very little during the P4 year. The vast majority of PG content was in required courses, with only a few courses being offered as an elective. There was wide variability in which course(s) PG content was taught. Biochemistry, pharmacokinetics, pharmacology and medicinal chemistry courses were most frequently listed. A smaller, but still significant percent of schools included PG content as part of clinical courses such as therapeutics. Little content appeared to be presented during the fourth professional year of most schools' curricula. This is most likely because students at that point are typically on rotations. Although PG was seldom taught formally during a student's final/rotation year, it would be interesting to investigate how much of the PG content students received during earlier didactic courses was actually utilized or expanded upon in the practice setting by preceptors or clinical faculty.
The actual range of PG-related topics was quite broad. Areas for which there is the greatest amount of published scientific information and current clinical application, such as the role of PG in drug metabolism, drug transport and specific disease states, were addressed with the highest frequency. A significant percentage (>70%) of schools with PG content also included information on human genomics as well as the role of PG in new drug development. It was interesting that more than half of the institutions that had PG content also included discussions related to bioethical issues, which is a topic of great importance. Teaching of actual PG methodologies received a less significant emphasis in the curriculum than did content related to the application of PG.
The overwhelming choice for delivering PG content was lecture. Almost all respondents reported supplementing lectures with instructor handouts. Interestingly, while nearly 70% of respondents assigned readings, there were no definitive textbooks, journals or even Web sites available to faculty. No single text, journal or Web site was listed more than once, a finding that clearly highlights the lack of appropriate written PG resources for pharmacists and pharmacy students. This lack of appropriate PG resources presents an excellent scholarship opportunity with regards to the development of PG-specific texts, journal articles and Web sites for pharmacists and pharmacy students.
Our final goal was to gauge the importance that faculty assign to students and pharmacy practitioners having knowledge in PG. The vast majority of respondents believed PG content was "very important" or "important" for all groups listed. The overwhelming majority of faculty believed it was "very important" for current PharmD students and health-systems practitioners to have PG knowledge; nearly as many felt it was likewise important or very important for community practitioners. Only 10% of our respondents agreed with the statement that only specialist pharmacists will need to know PG for their future practice; clearly most pharmacy faculty involved with PG believe PG knowledge will be important in the future practice of pharmacy.
The findings of this study are particularly timely given the recent commercial availability of pharmacogenomic testing that may be done directly by patients. Using a simple cheek swab, patients may obtain DNA tests by mail that detail their pharmacogenetic profile for drug classes such as antidepressants, anticoagulants and opioids in addition to their risk for certain drug reactions. Kits are also available to analyze a patient's CYP450 enzyme activity to determine if they are "fast," "slow" or "intermediate" metabolizers. It is likely that pharmacists will be asked to interpret test results and answer questions about adverse drug effects that might occur based on a patient's genetic CYP profile. It is also likely that additional home, Web or pharmacy-based tests for genetic variability will become available in the near future (e.g., the company marketing the home CYP test kits also plans to offer home test kits for N-acetyltransferase 2 in the near future). As a result, pharmacists must understand the basis of these pharmacogenomic tests along with their potential benefits and short-comings.
A recent interesting article by Brock[14] argued that genetic science and pharmacogenomics could revitalize the clinical role of pharmacists and generate new interest in pharmacy education and research. Brock stated that in order for current and future pharmacists to participate in the translation of pharmacogenomic advances into clinical practice, they will need to be trained in the interpretation, management, application and delivery of pharmacogenomic information. He also argued that as researchers, pharmacists can play a critical role in the implementation of novel drugs with highly specific, genetically-based targets, and new study methodologies tailored for pharmacogenetic research and development. This new PG-based drug development will require pharmacists to be well-educated in the ethical, social and legal issues of PG as they relate to clinical practice.
As a continuation of the current study, the authors intend to follow-up with additional surveys directed specifically at pharmacy preceptors and practicing pharmacists in community and hospital settings. These surveys will focus on how important these pharmacists believe PG knowledge is to their practice and to what extent they apply various aspects of PG in their daily practice. We also intend to repeat the original survey in approximately 3 years to identify whether or not the anticipated increase in PG content has occurred and to track additional changes.
The wide range of PG topics and the variation in curriculum placement suggest the need for a national dialogue focusing on 2 important questions. First, what PG topics are important for practicing pharmacists both now and in the future, and second, how can those topics best be integrated into pharmacy curricula?
Currently taught PG content is highly correlated with available published literature. While the topics of drug metabolism, drug transport, and specific disease states may be highly appropriate, others such as bioinformatics, the role of SNPs in drug response, and bioethics may be equally or even more important. It is important that we identify which topics are essential for practicing pharmacists, and then focus both research and educational efforts on those topics.
Finding the optimal curricular locations for these topics is also a critical issue. For example, should bioinformatics be included in current informatics courses or incorporated into discussions of the role of SNPs in drug response? Should PG-related ethical issues be concentrated within current bioethics courses or should they be addressed along with the role of SNPs in drug response, since SNP variations can have larger implications beyond that of drug metabolism?
Limitations
There are several limitations in the current study. While we did survey all schools of pharmacy in the U.S. and Canada, we did not separate compiled data based on the country from which it was returned. As a result we are unable to make any comparisons between PG content in U.S. and Canadian schools of pharmacy. Our survey was directed toward faculty actively involved in the presentation of PG content. It is likely these faculty might be biased in their opinions of how important this content is in the curriculum. We did not actively survey outside preceptors or other practicing pharmacists to gauge how important they felt PG knowledge was for current practice or what content would be most appropriate to include. Our survey package was sent directly to the deans of each of the various schools of pharmacy who were asked to forward the survey to the faculty best suited to complete the survey. In this respect the choice of who filled out the surveys was decided by the deans and not the survey authors. Finally, although we believe our survey response rate was good, results could differ significantly between responding and non-responding schools.
Conclusion
Schools of pharmacy appear to have been proactive in following the AACP guidelines for PG content in their curriculum. However, there was a wide scope of PG content and variable amounts of coverage across pharmacy curricula. The majority of respondents felt the amount of PG content in their current curriculum was inadequate; however, most believed the amount would increase in the future. There was no clear consensus on what content should be included, nor on which course should include significant PG content. Definitive texts, reference journals or Web sites are not available or are not widely used by pharmacy instructors presenting PG content. With regards to the value of PG education, content knowledge in PG was considered important for students of pharmacy as well as for pharmacists practicing in all areas.
Appendix A (Survey)
References
1. National Human Genome Research Institute, National Institutes of Health. Available at: http://genome.gov. Accessed November 11, 2005.
2. DNA Microarray (Genome Chip), Monitoring the genome on a chip. Available at: http://www.gene-chips.com. Accessed November 11, 2005.
3. The SNP Consortium Limited, single nucleotide polymorphisms for biomedical research. Available at: http://snp.cshl.org. Accessed November 30, 2005.
4. Weinshilbaum R. Inheritance and drug response. N Engl J Med. 2003;348:529-537.
5. Daly AK. Pharmacogenetics of the major polymorphism metabolizing enzymes. Fund & Clin Pharmacol. 2003;17:27-41.
6. Evans WE, McLeod HL. Pharmacogenomics, drug disposition, drug targets and side effects. N Engl J Med. 2003;348:538-545.
7. Watters JW, McLeod HL. Cancer pharmacogenomics: current and future applications. Biochim Biophys Acta. 2003;1603:99-111.
8. Chasman DL, Posada D, Subrahamnyan K, Cook NR, Stanton VP, Ridker PM. Pharmacogenetic study of statin therapy and cholesterol reduction. JAMA. 2004;291:2821-2827.
9. Mancama D, Kerwin RW. Role of pharmacogenomics in individualized treatment with SSRI's. CNS Drugs. 2003;17:143-151.
10. Pharmacogenomics: a scientific revolution in pharmaceutical sciences and pharmacy practice. Report of the 2001/02 Academic Affairs Committee. Available at: aacp.org/site/view.asp. P:\Committees\STANDING\academic affairs\01-02\Academic Affairs final report.doc. Accessed December 1, 2005.
11. Latif DA, McKay AB. Pharmacogenetics and Pharmacogenomics instruction in colleges and schools of pharmacy in the United States. Am J Pharm Educ. 2005;69:152-156.
12. Sansgiry SS, Kulkarni AS. The human genome project: assessing confidence in knowledge and training requirements for community pharmacists. Am J Pharm Educ. 2003;67:1-10.
13. Moridani MY. The significance of pharmacogenomics in pharmacy education and practice. Am J Pharm Educ. 2005;69:249-250.
14. Brock TP, Valgus JM, Smith SR, Summers KM. Pharmacogenomics: implications and considerations for pharmacists. Pharmacogenomics. 2003;4:321-330.
Clinical Course of Adult ADHD Patients Treated with Atomoxetine
Rachel E. Fargason, MD, Associate Professor, University of Alabama at Birmingham School of Medicine, Birmingham, AL
Marshall E. Cates, PharmD, BCPP, FASHP, Professor of Pharmacy Practice, Samford University, Birmingham, AL (Dr. Cates was also the Sponsoring Faculty for this student paper)
Pamela J. Sims, PharmD, PhD, Professor and Chair, Department of Pharmaceutical, Social, and Administrative Sciences, Samford University, Birmingham, AL
Angela A. Boggs, PharmD, Clinical Pharmacist, University of Maryland-Baltimore, MD
Abstract
Introduction: Atomoxetine was the first FDA approved non-stimulant for the treatment of adult ADHD. Very little is known about the clinical course of adult ADHD patients treated with atomoxetine, especially for cases involving comorbid psychiatric disorders.
Methods: The design was a retrospective study of adult ADHD patients treated with atomoxetine at a specialized clinic. The primary efficacy measure was the Clinical Global Impressions-Improvement scale.
Results: Thirty-seven patients were enrolled into the study, most of whom were also diagnosed with depression (24/37). Approximately one-half (18/37) of patients were rated as responders to therapy based on CGI-I score of 1 or 2. Those patients with comorbid psychiatric disorders had a higher response rate than did those patients without comorbid psychiatric disorders (56% vs. 33%). Most patients were switched to atomoxetine from previous therapies, but those cases in which atomoxetine was added to existing drug therapy showed a higher response rate. Therapy was discontinued in 21 cases, usually owing to adverse effects (11/37). Men were more than twice as likely as women to discontinue therapy due to adverse effects.
Conclusions: Atomoxetine therapy was effective for adult ADHD patients, especially those with comorbid depression ± anxiety. Atomoxetine therapy was particularly effective as an adjunctive agent in cases of partial response to previous therapy. The discontinuation rate due to adverse effects was comparatively high, especially for male patients.
Key words: atomoxetine, attention-deficit/hyperactivity disorder, adult ADHD
Introduction
Attention deficit/hyperactivity disorder (ADHD) is typically first evident in childhood, noted by excessive motor activity, difficulty in sustaining attention, and impulsiveness.[1-4] Historically, clinicians believed that ADHD was a condition that would be "outgrown" in puberty or adulthood, but there is now evidence that a significant number of cases will have symptoms that persist into adulthood.[1,5] Adult ADHD has been associated with higher levels of school failure, poor work history, and low self-esteem.[5] Adult patients seem to have a more difficult time dealing with the stress of everyday life, especially for those trying to balance work with household management and family planning. Furthermore, adult ADHD is frequently complicated by comorbid mood disorders and substance abuse.[2-3]
While many modalities may be utilized in treatment for adult ADHD, including support groups, coping strategies, skills training, and coaching to handle difficult situations, pharmacotherapy remains first line in the effective management of the disorder.[2-5] Stimulant therapy has been the treatment of choice, showing the greatest amount of efficacy compared to tricyclic antidepressants and bupropion, which have also been used in treatment of ADHD treatment.[2-4] Methylphenidate and mixed amphetamine salts are the agents of choice; however, caution must be used in patients with substance abuse potential. The longer-acting preparations are better tolerated and have lower abuse potential.[3-4] Adverse effects from stimulants are generally mild and may include decreased appetite, insomnia, headache or nervousness. [4] Tricyclic antidepressants have shown moderate improvement for adult patients with ADHD, however the side effect profile tends to be more severe. Constipation, dry mouth, postural hypotension, and tachycardia may be experienced.[3-4]
The newest treatment option, and the first FDA approved non-stimulant indicated for the treatment of adult ADHD, is atomoxetine (Strattera®).[6] Atomoxetine is a selective norepinephrine reuptake inhibitor with mild antidepressant activity.[6-7] It does not affect extracellular dopamine levels in the striatum or nucleus accumbens, a brain region associated with psychostimulation and rewarding properties of drugs of abuse.[6] Atomoxetine is considered a valuable treatment option, especially in patients with substance abuse potential or those not wishing to take a controlled substance.[8]
Two nearly identical, randomized, controlled clinical trials were conducted in adults to establish safety and efficacy of atomoxetine in ADHD.[9] In the first trial, 280 adults between 18 and 67 were included to take either atomoxetine (n=141) or placebo (n=139) twice daily, in the morning and early evening for 10 weeks. The second trial included 256 adults between 18 and 76 to take either atomoxetine or placebo twice daily, in the morning and early evening for 10 weeks.[9] The total daily dose (TDD) was 60mg at the initiation of the trial and was titrated up to 120mg TDD at 4 weeks, if needed, based on patient response. Patients were required to have verifiable symptoms of ADHD in childhood, persisting into adulthood. Patients were excluded if they had concurrent anxiety or depression, past or current psychotic or bipolar disorders, serious medical illness, or alcohol or substance abuse. The primary endpoint, reduction in total ADHD symptoms, was measured by the Conners' Adult Attention Rating Scale (CAARS), which is completed by the patient and/or an observer such as a spouse, parent, or friend. It uses a scale of 0-4 (not at all, just a little, pretty much, very much). The Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) ADHD criteria can be extracted from CAARS, which validates its usefulness in these trials. In both studies, atomoxetine demonstrated statistically significantly improved CAARS scores versus placebo. No significant differences were seen based on population subsets of gender or age.[6,8] In both trials, atomoxetine was well tolerated, as adverse effects were generally mild and transient. Only 9 of the 270 patients treated with atomoxetine withdrew from the trials due to treatment-related adverse effects: insomnia (n=3), chest pain (n=2), palpitations (n=2), and urinary retention (n=2.[8]
Atomoxetine was introduced to the market in December 2002, holding what many clinicians believed was great promise for a new type of treatment for adult ADHD. However, there have been no trials following the natural clinical course of patients who where treated with atomoxetine as either monotherapy or adjunctive therapy to determine its long-term safety and efficacy. Furthermore, trials typically exclude patients with comorbid psychiatric disorders.[6] The majority of adult ADHD patients in clinical practice suffer from comorbid psychiatric disorders. The purpose of this study was to determine the efficacy and tolerability of atomoxetine therapy for adult ADHD in the usual clinical setting.
Methods
This study was approved by the Institutional Review Boards of Samford University and University of Alabama at Birmingham (UAB). A waiver of informed consent was obtained prior to the study. The study was conducted at the adult ADHD clinic of UAB. A computerized search of medical records was conducted to identify the names of all patients who had the diagnosis of attention deficit disorder with or without hyperactivity electronically coded on a visit in the adult ADHD clinic at the University of Alabama at Birmingham. All charts were reviewed to select patients meeting the following inclusion criteria: ages 19-65; diagnosed with ADHD of any subtype; prescribed atomoxetine as monotherapy or adjunctive therapy since December 2002; had at least an initial assessment and one follow-up session with documented adverse effect and efficacy data.
Data collection included demographic information, comorbid disease states, concurrent psychotropic medications, and clinical course for treatment of ADHD. The progress notes were evaluated for efficacy using the Clinical Global Impression for Improvement scale (CGI-I) at the most recent follow-up visit as compared to the baseline visit when atomoxetine therapy was initiated.[10] Safety was evaluated based on adverse effects recorded by the clinician at each follow-up visit. Adverse effects were categorized as those causing termination of therapy and those not causing termination of therapy.
The CGI-I is a widely used tool to determine outcome measures in treatment studies of psychiatric disorders. The investigator determined CGI-I rating based on the data collected from the last recorded follow-up visit. The CGI-I is a scale from 1-7 that quantifies a clinician-rated global impression of improvement in the patient's psychiatric illness based on the following modifiers: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, or 7 = very much worse. Ratings were performed by 2 of the authors (Wilson & Fargason) based on assessments of treatment response as recorded in progress notes (originally written by Fargason). As determined by the investigators prior to data collection, patients with a CGI-I rating of 1 or 2 were considered responders.[10]
Results
A total of 224 patient charts were reviewed for inclusion in the study, with a total of 37 meeting inclusion criteria. All excluded subjects either did not have a diagnosis of ADHD or had never been treated with atomoxetine. The average age of patients was 42.4±12.3 years. Twenty-five patients had comorbid psychiatric disorders, and over 75% (28/37) were receiving other psychotropic medications. Other demographic information is presented in Table 1.
Nearly one-half (18/37) of patients responded to atomoxetine therapy. Only 5.4% (2/37) of patients had worsening symptoms upon treatment with atomoxetine. The remaining 45.9% of patients were either only minimally improved or had no change in symptoms.
Response rates across age groups were as follows: 19-25: 75.0% (3/4); 26-35: 33.3% (2/6); 36-45: 25.0% (2/8); 46-55: 64.3% (9/14); and >55: 40.0% (2/5). Males responded at a rate of 50.0% (12/24) and females responded at a rate of 46.2% (6/13).
Of the 25 patients with comorbid psychiatric disease states, 14 (56.0%) were responders. Of the 12 patients without comorbid psychiatric disease states, only 4 (33.3%) were responders. Patients with a diagnosis of depression had a response rate of 60.0% (9/15). Patients with depression and anxiety had a response rate of 57.1% (4/7).
In approximately one-half of the cases, atomoxetine therapy was initiated via switch from another medication (Table 2). For about one-third of cases, atomoxetine was initiated as monotherapy. A very high response rate (71.4%) was seen in the minority of patients (n=7) who had atomoxetine added to their existing medication for treatment of ADHD.
Endpoints of therapy are delineated in Table 3. Sixteen patients were receiving atomoxetine therapy at the time of data collection, including 5 who had another medication added to atomoxetine therapy due to partial response. Atomoxetine therapy was discontinued in more than one-half of cases, usually due to adverse effects.
Male patients discontinued therapy due to adverse effects at a higher rate than did female patients (Table 4). Sexual dysfunction was the most common adverse effect leading to therapy discontinuation. One patient experienced a hypertensive response, which was considered a severe adverse effect. All adverse effects mentioned in the progress notes were included, but the causal effect of atomoxetine is uncertain.
Adverse effects reported that did not result in termination of therapy are shown in Table 5. Fatigue and irritability were the most common adverse effects. Females were more likely to report fatigue, whereas males were more likely to report irritability.
Discussion
Approximately one-half of adult ADHD patients responded to treatment with atomoxetine based on the categorical endpoint of CGI-I of 1 or 2. Not surprisingly given the mild antidepressant effects of atomoxetine, subjects with a concurrent diagnosis of depression responded at a higher rate than those patients lacking this comorbidity. While some of these patients were also being treated with antidepressants, the antidepressant dosages remained the same during the 2-month period of atomoxetine initiation. Of all patients with comorbid psychiatric disease states, 56% were responders. According to a recent treatment guideline[11], atomoxetine can be used for patients with mood, anxiety, or substance use disorders.
The efficacy data are promising considering that many adult patients are diagnosed with ADHD while being treated for other psychiatric disorders. Another intriguing finding was that over 70% of patients who were prescribed atomoxetine in addition to an existing regimen for ADHD were responders to therapy. Thus, atomoxetine may be particularly effective as an adjunctive agent in the treatment of ADHD.
As anticipated based on the aforementioned phase III trials, atomoxetine caused mainly mild adverse effects, as only one adverse effect was considered severe by the investigators. However, the percentage of our patients who had therapy terminated due to adverse effects--almost 30%--was greater than expected. This could possibly be due to differences between the experimental procedures of phase III trials versus usual clinical practice reflected in the present trial. Interestingly, the percentage of males terminating therapy due to adverse effects was considerably greater than that of females (37.5% versus 15.4%, respectively). The most common adverse effect resulting in termination of therapy was sexual dysfunction. In the phase III trials, no subjects discontinued therapy due to sexual dysfunction, although the adverse event was reported in 12% of subjects. There were also significant differences between genders in the rate of occurrence of certain adverse effects. Fatigue was reported in 7 (53.8%) females vs. 2 (8.3%) males. Urinary hesitancy was reported by 3 (12.5%) males vs. 0 (0.0%) females. Finally, 4 (16.6%) males vs. 0 (0.0%) females reported irritability as a result of atomoxetine therapy. While the cause is unknown, these results introduce the possibility of different adverse effect profiles for patients based on gender.
Limitations
Obvious limitations of the study include its retrospective design and small sample size; however, it is difficult to find a large sample size in a clinic specifically dedicated to adult ADHD. Since response to therapy was determined with a global measure of improvement (i.e., CGI), it is impossible to demarcate improvement of primary symptoms of ADHD versus symptoms of comorbidities.
Adverse effects may have been underestimated due to the retrospective design of the trial (i.e., the patients may have experienced adverse effects that were not recorded in the progress notes). Furthermore, investigators were unable to determine the absolute causation of adverse effects due to the number of variables, such as self-medication with herbals or OTC drugs or concurrent prescription medication. Any adverse effect the patient reported was listed as a possible result of atomoxetine. Reported adverse effects did occur in temporal relationship with initiation of atomoxetine therapy while other medications were held constant.
We were unable to assess compliance, as this data was not always recorded in the charts. Also, patients were able to terminate therapy at any time, with or without the presence of a valid reason for cessation. These factors negatively effect results as they may skew data that otherwise might have appeared more positive. Generalizability of findings is a concern because the study was conducted at a single clinic. Also, all of the subjects were Caucasian.
Conclusions
Despite the limitations of this study, atomoxetine should be considered a valuable treatment option for adult patients with ADHD, especially those with concurrent depression and anxiety symptoms. The majority of patients showed at least minimal improvement with only mild adverse effects, as was anticipated based on previous data from other studies. However, the discontinuation rate due to adverse effects was relatively high, especially for male patients. Further controlled clinical trials with more diverse populations are needed to further characterize the role of atomoxetine therapy in the adult ADHD population.
References
1. Westfall TC, Westfall DP. Adrenergic agonists and antagonists. In: Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman's: The Pharmacological Basis of Therapeutics.11th ed. New York, NY:McGraw-Hill; 2006:263.
2. ADHD in adults. CHADD Web site. Available at: www.chadd.org. Accessed October 15, 2006.
3. Adler LA, Chua HC. Management of ADHD in Adults. J Clin Psychiatry. 2002;63(suppl 12):S29-35.
4. Weiss M, Murray C. Assessment and management of attention-deficit hyperactivity disorder in adults. CMAJ. March 18, 2003;168(6):715-722.
5. Spencer T, Biederman J, Wilens T, Faraone SV. Adults with attention-deficit/hyperactivity disorder: a controversial diagnosis. J Clin Psychiatry. 1998;59(suppl 7):S59-68.
6. Corman SL, Fedutes BA, Culley CM. Atomoxetine: the first non-stimulant for the management of attention-deficit/hyperactivity disorder. Am J Health-Syst Pharm. 2004;61:2391-2399.
7. Strattera [package insert]. Indianapolis, IN: Eli Lilly and Company; 2005.
8. Simpson D, Plosker GL. Spotlight on atomoxetine in adults with attention-deficit hyperactivity disorder. CNS Drugs. 2004;18(6):397-401.
9. Strattera clinical trial information page. Eli Lilly Web site. Available at: http://www.strattera.com/1_1_about_strattera/1_1_2_clinical.jsp. Accessed: October 15, 2006.
10. Sajatovic M, Ramirez LF. Clinical Global Impressions. Rating Scales in Mental Health. Hudson, OH: Lexi-Comp Inc;2001:164-165.
11. Drugs for treatment of ADHD. Treat Guidel Med Lett. 2006;4:77-82.
Updated
Novermber 13, 2006