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The changing face of cancer in Australian medical schools

A multitude of changes are revolutionising the study and practice of oncology worldwide.   Despite the undeniable importance of cancer education, there is currently no consensus amongst Australian medical schools as to what should be taught regarding oncology practice, nor have the best ways of teaching and learning about cancer been fully elucidated in the literature, or in the clinical realm. There is a lack of important cancer knowledge amongst graduating medical students and variation exists amongst individual Australian medical faculties, between states as well as individual universities from the same state. Furthermore, there is very little teaching here in Australia in relation to emerging genomic technologies within oncology, and in particular, the ever-increasing role of personalised and preventative medicine in cancer care today. Ultimately, there is a clear need for an integrated, overarching national oncology curriculum, embracing a patient-centred approach; national evaluation and assessment; supplementary courses; utilisation of self-directed learning and reflective practice activities; and greater emphasis on emerging technologies. With more research focus on this area, in future there may be a larger evidence-base targeted at providing improvements in Australian Oncology education, assisting graduates in gaining adequate understanding and appreciation of cancer-related scenarios and cancer care. More effective teaching and learning facilitation, with better overall Australian training outcomes, will lead to advancement in cancer diagnosis, treatment, and management as well as ensuring more insightful and valuable patient interactions in the future.

Introduction

A multitude of changes are revolutionising the study and practice of oncology worldwide.  The ways in which oncology and cancer care are incorporated into medical school curricula in Australia is thus of particular interest. Despire the undeniable importance of cancer education, there is currently no consensus amongst Australian medical schools as to what should be taught in regards to oncology practice, nor have the best ways of teaching and learning about cancer and cancer care been fully elucidated in the literature or in the clinical realm [1-4].

In Australia, there is considerable variation in undergraduate and postgraduate teaching of oncology amongst individual medical faculties [8,9] and a lack of important cancer knowledge amongst graduating medical students, between states and between individual universities from the same state [8,9,10]. This inconsistency is compounded by the nature of oncology as a multidisciplinary specialty, with overlap in numerous fields including pathology, surgery, histology, radiology, anatomy, genetics, communication skills, and palliative care [1].

Further, there is very little teaching here in Australia in relation to emerging technologies within oncology and in particular, the ever-increasing role of personalised and preventative medicine in cancer care today. Educators are now presented with the inevitable task of addressing all foundational educational needs in our generation of medical graduates. They must also ensure to incorporate pertinent aspects of such a rapidly progressive field of medicine as it relates, for example, to genetic testing and counselling, the rise of personalised or ‘precision’ medicine, and ongoing development in cancer immunotherapies [11-14].

Variation in oncology education in Australia is compounded by the lack of literature on this subject, which is predominantly qualitative in nature and overall, more difficult to evaluate [30].  Whilst cancer is the number one cause of death in Australia, oncology itself is still not a subscribed part of the medical curriculum, nor is an oncology rotation compulsory in Australian medical schools. There is an ongoing lack of literature regarding oncology-specific teaching and learning methods, as well as a lack of evidence in the effective implementation of compulsory curricula or rotations to engage with foundational and emerging aspects of oncology or palliative care.

The importance of this issue resonates with students, recent graduates, and educators as all medical students will at some point in their career play a role in the management of a cancer patient [5], whether as a resident on an oncology rotation, as a general practitioner at the stage of diagnosis, during long-term follow-up of a cancer survivor [6], as a fully-qualified oncologist, or as a clinical geneticist. Furthermore, with our ageing Australian population, there will be greater numbers of individuals diagnosed with and treated for cancer than ever before as well as an increased number of survivors, making cancer a chronic illness to be managed by a multidisciplinary team [7].

 

How did we get here?

In 1993, the General Medical Council published a detailed review of medical education [15], which led to a major overhaul of medical school oncology training in the United Kingdom, and worldwide [1,16].  A survey of European universities showed that 95% indicated the need for increased cancer education and there was an overwhelming interest in a common European oncology curriculum [17].

In 1999, and again in 2007, the Ideal Oncology Curriculum (IOC) for Medical Students was released here in Australia [18], produced by the Oncology Education Committee of the Cancer Council Australia and endorsed by the Union for International Cancer Control (UICC). It provides an unparalleled example of the evidence-based recommendations required for medical school cancer education, including prescribed clinical experiences and knowledge attainment, which necessitate a patient-centred approach to training methods. In each section, there is detail of prerequisite knowledge, as well as a list of representative questions that illustrate the ‘required depth of knowledge’ for graduating medical students, with attached example answers and multiple-choice question-answer options.

Focus is on the patient rather than the discipline, with topics ranging from public health and cancer biology, to patient management, diagnosis, communication skills, and clinical experiences [18]. More recently, it has been supplemented by a detailed e-Book entitled “Clinical Oncology for Medical Students”, which may be utilised alongside the recommended experiential learning, and acquisition of technical oncology skills, for a more robust understanding of the prescribed IOC material [19].

Moreover, the World Health Organisation and UICC recommend that cancer education be incorporated into oncology modules within an undergraduate curriculum and that medical students spend a minimum of two weeks in oncology training [4,5]. However, despite the superlative example given by the IOC, there has been minimal uptake in Australia, which may be linked to the current lack of a national curriculum, the dearth of literature on effective educational strategies, or the historical absence of oncology content in Australian medical school curricula. This lack of implementation and an inadequate evidence-base makes the feasibility and effectiveness of oncology rotations or uptake of the IOC guidelines incredibly difficult to ascertain, let alone, achieve.

 

Oncology teaching and learning methods

Internationally, there has been a push for an overarching pre-clinical oncology curriculum for medical students incorporating medical knowledge, psychosocial aspects, communication skills training, and utilisation of a variety of teaching methods such as interviews, discussion, reflection, and lectures [1,2,7,20].

There is increased emphasis on a patient-centred approach to teaching [11,13] and learning in oncology education [22,23]. This should extend from the use of standardised patients teaching examination skills to medical students, to the involvement of cancer patients in communication skills teaching and portfolio learning [1,24].

Self-directed learning (SDL) is the educational strategy considered most likely to produce medical graduates who are prepared for lifelong learning and who are able to meet the needs of their patients [26,30]. SDL activities include problem-based learning (PBL), discovery learning, task-based learning, experiential and reflective learning, portfolio-based learning, small group or project-based learning, and peer evaluation with learning contracts [26]. Results from numerous studies have indicated a trend towards improved student performance from SDL assessment, as with the follow-up of a cancer patient over an extended period of time [1,21,23-25]. The use of portfolio assessment and learning journals is also championed as a tool of successful oncology training and for lifelong education [25]. An array of methods may thus be employed in undergraduate oncology training whilst utilising the SDL approach [26-27].

The PBL approach, more specifically, as one of the major aspects of SDL, facilitates a deeper learning style [28] and involves an active search for understanding based on a given scenario. This technique is linked to better clinical problem-solving skills in medical students with higher levels of motivation and stimulation found [27] and superior outcomes in students tested [9,29].

Regarding format, some have argued that an independent block style is more effective in presenting an oncology curriculum [20]. This is as opposed to an integrated model of teaching into other system modules and would be relevant within an Australian-based system. In block format, the curriculum may be presented through oncology-specific technology-based lectures, team-based communication, and clinical skill exercises supplemented by lectures paired with relevant clinically-based scenarios and other activities posted online to be worked through independently [20].

Computer-aided learning [1,21,22,30] may itself have a role to play as supplementation to oncology study though technology-based approaches are not necessarily superior to other learning techniques [1]. Here in Australia, a number of medical schools are already utilising the e-Learning Undergraduate Modules for Australian Medical Schools, accessible via The e-Learning Portal, which is provided by The Australasian College of Dermatologists [31]. This is highly applicable on a national level when considering skin cancer rates in Australia [32]. Overseas, an ‘eDerm’ online curriculum [33] provided to 252 medical students in the United States significantly improved the diagnosis and management of pigmented skin lesions by medical students [33].

In regards to communication skills, suboptimal communication can lead to adverse psychological effects in patients. It can compromise a physician’s ability to treat patients, as well as impacting patient satisfaction, medication compliance and overall clinical outcomes [34]. The use of group presentations, small-group communication skills practice [35], and reflective self-awareness exercises have been shown to improve communication skills. This is particularly true with the use of patient-actors in simulated clinical situations as opposed to role-play alone. There is overwhelming proof that communication skills can be taught and should be delivered through experiential learning methods, which are ultimately more effective than instructional modes to address communication skills development in oncology [36].

Moreover, a primary skill that any medical student can bring to an oncology experience, or rotation is their presence and their time. Medical student training in this burgeoning field [11] must facilitate the development of essential communicative abilities: to be able to listen to a cancer patient’s story during their clinical journey, to be able to connect with this experience, and communicate effectively in response to this scenario [18,34-36].

 

Lessons from abroad

At the University of Wales’ College of Medicine, medical students followed a patient along their cancer journey over a six-month period and were assessed during patient interactions and through a final portfolio. Overall, students found the project rewarding and reported gaining unparalleled insight into the cancer experience [22].

A three-day intensive oncology course has been piloted in Israel, with students feeling more comfortable with cancer-related issues, less afraid of dealing with death, and better able to cope with uncomfortable cancer-related emotional situations as a result [7]. Psychosocial and ethical aspects were presented through student-led presentations and discussions, a psycho-oncology session led by a psychologist, and two presentations by cancer patients describing their personal experiences and offering advice on aspects such as the doctor-patient relationship [7].

In Poland, attempts have been made to improve cancer education through the National Program for Combating Neoplastic Diseases [16]. This was done with a course incorporating computer-learning modules, online tests, portfolio learning, summer school, modules taught by cancer patients, and attachments in oncology and palliative care. Observations highlighted that the introduction of these courses better prepares students for delivering cancer care [16].

Finally, in a novel Brazilian experience, students staffed an oncology clinic, with 77% of students involved in this approach over a ten-year period rating it as the best activity of their course. Findings suggested that attendance at an oncology outpatient clinic can contribute significantly to the cancer education of medical students [24].

 

Future directions for Australian oncology education

There is a clear need for the following in cancer education:

  1. An integrated, overarching national curriculum, with a patient-centred approach
  2. National evaluation and assessment
  3. Summer schools and supplementary courses
  4. Embracing SDL & PBL, with reflective practice activities
  5. Greater emphasis on emerging technologies

 

  1. An oncology curriculum, with a patient-centred approach

 A relevant, integrated oncology curriculum as detailed by the IOC [15,18] should be embraced by all Australian medical schools, with the aim of bringing together requirements regarding essential knowledge, skills, and attitudes about cancer and cancer-related care [2,8,9,10,17]. It should be well-rounded and ideally supported by a coordinating body, with an academic basis of professorships [2].

 As detailed by the IOC [18], there is a need for increased emphasis on clinical interaction and greater time spent with patients [1,2,5,21,37]. As suggested [18], medical students need at least five cancer clinical experiences before graduating:

  • Talking with and examining people affected by all stages of cancer;
  • Talking with and examining people affected by all common cancers;
  • Observing all components of multidisciplinary cancer care;
  • Seeing shared decision-making between cancer patients and their doctors; and
  • Talking with and examining dying people [2,15,18].

 

  1. Assessment

As shown in Australian medical schools, assessment drives performance [2]. Thus, having decided upon a particular patient-centred approach, carrying out formal evaluation of student learning and course content is vital for enhancing training outcomes [18,38], and should inform the prescribed curriculum [2]. In future, this might include the introduction of national assessment, such as a national exit examination [40], with oncology-related scenarios aimed at testing core knowledge levels and ensuring standardisation is maintained across the country [9,39,40].

 

  1. Supplementary courses 

Regarding adjuncts to a proposed national curriculum and module [20] of oncology teaching, summer schools and extra courses [7,16] may be of great use here in Australia [1]. The Vienna Summer School, for example, receives high levels of praise and acceptance rates from European medical students. These students note that these supplementary courses provide them with a greater understanding of oncology and an appreciation of its’ multidisciplinary character [15]. Summer schools may offer educational activities that fill the gaps of an otherwise disjointed oncology training program, as shown by the example of oncology summer schools in Europe [4].

 

  1. Self-directed learning, problem-based learning and reflective practice

Learning in medical school is rarely fully autonomous, with students valuing pedagogic support and often relying on teachers as coordinators and facilitators of their learning environment [41]. Students should be encouraged to recognise the importance of evidence-based medicine, how to critically appraise literature, and the need to constantly update one’s knowledge based on high-quality evidence and guidelines [18]. Furthermore, team-based learning through small scenario or discussion groups has a role to play in the application of basic science knowledge to real-world oncology-related scenarios [35]. This could lead to greater engagement with lecture content and its’ application in daily medical practice.

There is increasing necessity for our medical curriculum to foster the development of sound communication skills. Furthermore, providing students at every level of their education with an opportunity for reflective practice, as individuals and in smaller groups, is also a must. This may serve as an important tool in supporting students who emotionally encounter negative experiences as a result of difficult or uncomfortable clinical encounters. Mentoring, as an extension of this pathway, may be of use in allowing reflection following hospital experiences. It may be of use for medical students to attach themselves to ‘mentor’ clinicians on rotation, staff whom they perceive to be effective teachers for coaching purposes, development of reflective practice, and consolidation of learning [42].

Moreover, students learn more effectively by being actively involved in a PBL strategy, as it facilitates epistemic curiosity through activation and elaboration of prior knowledge [22]. Reflection on experience, followed by evaluation, analysis, and appropriate action, may facilitate further learning and appreciation of curriculum content in the Australian context [1,4,18,21,22,23,25]. Portfolio learning [1,22,23] should thus be employed in a set teaching program [16,23], with reflective exercise  and a compulsory portfolio-based experience, or assessment. This would to facilitate reflection and exploration of the patient experience along their cancer trajectory.

 

  1. Emphasis on emerging technologies

Dramatic advances in genomic technology stand to revolutionise clinical cancer care [13,14]. Personalised (or ‘precision’) medicine is a banner term, describing the use of molecular tools to individualise healthcare through genetic testing, whole genome sequencing, exome, or transcriptome sequencing [13]. While there has been ample research in the area of genetic testing and its’ implications for our future, very little is known about how best to encourage development in understanding of such technologies at the level of medical students or recent graduates.

In the realm of breast cancer in Australia, for example, an individualised cancer care approach is evidenced in the case of genetic testing for BRCA1/2 mutations, which reflect a specific predisposition toward breast and ovarian cancer [43]. About 5% of cases of breast cancer and 10% of ovarian cancer cases, are due to such inherited predisposition [44,45]. With progress towards a more personalised, family-centred model of oncological care in Australia, knowledge of ones’ genetic and genomic information plays a crucial role, from screening and prevention, to individualised surgical treatment, and utilisation of targeted therapies based on a tumours’ molecular signature [46].

In order to fully realise the effective application of personalised medicine into routine Australian cancer care, students and clinicians need a more comprehensive understanding of emerging technologies. In addition, an appreciation of the experiences, and attitudes of cancer patients, and their families is required. Evidence suggests that the majority of cancer patients are willing to undergo genetic and genomic testing during, or following, cancer treatment [11]. More work is needed in this area to provide graduates with a more refined appreciation of how best to communicate genomic concepts to a broad range of patients [11]. Medical graduates must have greater awareness of foundational genetics-based and personalised medicine pathways. This will allow them to alleviate patient misconceptions and ultimately, to empower patients to make more informed cancer care decisions [12-14]. Without this, there may be failure to adequately deliver genetically-guided cancer care, treatment, and management in the future. The issue our educators will now face is how to best integrate this information into a feasible medical student curriculum.

 

Conclusion

More effective teaching and learning strategies in oncology should be aimed at producing Australian medical graduates with adequate and relevant cancer-related knowledge, skills, and attitudes that best meet the needs of their society [2]. The IOC [18] does an exceptional job of demonstrating the requirements and expected knowledge to be attained through a prescribed oncology curriculum here in Australia.

Australian medical students need a well-rounded understanding of oncology concepts and appropriate examination and communication techniques to facilitate aspects of cancer diagnosis, referral, and management in future clinical practice [20]. There must be focus given to developing an awareness of emerging technologies in the realm of cancer care with emphasis on basic concepts related specifically to genetic testing, genetic counselling, and personalised medicine.

The foundational experiences provided by medical school training serve to shape one’s entire career as a doctor. Those students more engaged in their learning through SDL, PBL and reflective practice strategies [26,27], and who have a greater understanding of key concepts are more likely to achieve superior assessment outcomes [2]. They are also more likely to be involved in successful clinical interactions overall [1].

With greater research focus on this area in future, there may be a larger evidence-base targeted at providing overarching improvements in Australian oncology education. This will assist graduates in gaining an adequate understanding and an appreciation of cancer-related scenarios and cancer care. More effective teaching and learning facilitation with better overall Australian training outcomes will ultimately lead to advancement in cancer diagnosis, treatment, and management outcomes as well as ensuring more insightful and valuable patient interactions in our futures [5,12].

 

Conflicts of interest

None declared.

 

References

  1. Gaffan J, Dacre J, Jones A. Educating undergraduate medical students about oncology: a literature review. Journal of clinical oncology. 2006;24(12):1932-9.
  2. Barton MB, Bell P, Sabesan S, Koczwara B. What should doctors know about cancer? Undegraduate medical education from a societal perspective. The Lancet Oncology. 2006;7(7):596-601.
  3. Fromm-Haidenberger S, Pohl G, Widder J, Kren G, Fitzal F, Bartsch R, et al. Vienna international summer school on experimental and clinical oncology for medical students: an Austrian cancer education project. Journal of Cancer Education. 2010;25(1):51-4.
  4. Pavlidis N, Vermorken JB, Stahel R, Bernier J, Cervantes A, Audisio R, et al. Oncology for medical students:: A European School of Oncology contribution to undergraduate cancer education. Cancer Treatment Reviews. 2007;33(5):419-26.
  5. Payne S, Burke D, Mansi J, Jones A, Norton A, Joffe J, et al. Discordance between cancer prevalence and training: a need for an increase in oncology education. Clinical Medicine. 2013;13(1):50-6.
  6. Practitioners RACoG. The RACGP Curriculum for Australian General Practice: RACGP 2016 Curriculum. Melbourne: The Royal Australasian College of General Practitioners. 2016.
  7. Granek L, Mizrakli Y, Ariad S, Jotkowitz A, Geffen DB. Impact of a 3-Day Introductory Oncology Course on First-Year International Medical Students. Journal of Cancer Education. 2016:1-7.
  8. Smith WT, Tattersall MHN, Irwig LM, Langlands AO. Undergraduate education about cancer. European Journal of Cancer and Clinical Oncology. 1991;27(11):1448-53.
  9. McGrath BP, Graham IS, Crotty BJ, Jolly BC. Lack of integration of medical education in Australia: the need for change. Medical journal of Australia. 2006;184(7):346.
  10. Tattersall MHN, Langlands AO, Smith W, Irwig L. Undergraduate education about cancer. A survey of clinical oncologists and clinicians responsible for cancer teaching in Australian medical schools. European Journal of Cancer. 1993;29(11):1639-42.
  11. Gray SW, Hicks-Courant K, Lathan CS, Garraway L, Park ER, Weeks (2012). Attitudes of patients with cancer about personalized medicine and somatic genetic testing. Journal of Oncology Practice; 8(6): 329-35.
  12. McGowan ML, Settersten RA Jr, Juengst ET, Fishman JR. (2014). Integrating genomics into clinical oncology: ethical and social challenges from proponents of personalized medicine. Urologic Oncology; 32(2): 187-92.
  13. Tian Q, Price ND, Hood L. (2012). Systems cancer medicine: towards realization of predictive, preventive, personalized and participatory (P4) medicine. Journal of Internal Medicine; 271(2): 111-21.
  14. Ward RL. (2014). A decade of promises in personalised cancer medicine: is the honeymoon over? The Medical Journal of Australia; 200(3): 132-3.
  15. General Medical Council. Education C. Tomorrow’s doctors: recommendations on undergraduate medical education: General Medical Council London; 1993.
  16. Matkowski R, Szelachowska J, Szewczyk K, Staszek-Szewczyk U, Kornafel J. Improvements in undergraduate oncology education introduced at Polish Medical Universities between 2004 and 2010 under Poland’s “National Program for Combating Neoplastic Diseases”. Journal of Cancer Education. 2014;29(3):428-33.
  17. Robert KH, Einhorn J, Kornhuber B, Peckham M, Zittoun R. European undergraduate education in oncology: a report of the eortc Education Branch. Acta Oncologica. 1988;27(4):423-5.
  18. Oncology Education Committee. Ideal oncology curriculum for medical schools. The Cancer Council Australia. 2007.
  19. Sabesan S, Olver I, editors. Clinical Oncology for Medical Students. Sydney: Cancer Council Australia. [Version URL:http://wiki.cancer.org.au/oncologyformedicalstudents_mw/index.php?title=Clinical_Oncology_for_Medical_Students&oldid=1656, cited 2016 Oct 4]. Available from:http://wiki.cancer.org.au/oncologyformedicalstudents/Clinical_Oncology_for_Medical_Students.
  20. DeNunzio NJ, Joseph L, Handal R, Agarwal A, Ahuja D, Hirsch AE. Devising the Optimal Preclinical Oncology Curriculum for Undergraduate Medical Students in the United States. Journal of Cancer Education. 2013;28(2):228-36.
  21. Matkowski R, Szelachowska J, Szewczyk K, Staszek-Szewczyk U, Kornafel J. Improvements in undergraduate oncology education introduced at Polish Medical Universities between 2004 and 2010 under Poland’s “National Program for Combating Neoplastic Diseases”. Journal of Cancer Education. 2014;29(3):428-33.
  22. Maughan TS, Finlay IG, Webster DJ. Portfolio learning with cancer patients: an integrated module in undergraduate medical education. Clinical Oncology. 2001;13(1):44-9.
  23. Finlay IG, Maughan TS, Webster DJT. A randomized controlled study of portfolio learning in undergraduate cancer education. MEDICAL EDUCATION-OXFORD-. 1998;32:172-6.
  24. Abrão MN, Bensi CG, Gonçalves MS, Narahara JL, Otsuka FC, Ranzatti RP, et al. A medical student-staffed outpatient oncology clinic: a 10-year Brazilian experience. Journal of Cancer Education. 2008;23(1):63-4.
  25. Orr B. Learning in oncology: lessons from the 20th century, learner-centred education for the 21st century: part II. Clinical oncology. 2004;16(6):435-8.
  26. Spencer JA, Jordan RK. Learner centred approaches in medical education. British Medical Journal. 1999;318(7193):1280.
  27. Barrows HS. Problem-based learning in medicine and beyond: A brief overview. New Directions for Teaching and Learning. 1996;1996(68):3-12.
  28. Newble DI, Entwistle NJ. Learning styles and approaches: implications for medical education. Medical Education. 1986;20(3):162-75.
  29. Newble DI, Clarke RM. The approaches to learning of students in a traditional and in an innovative problem-based medical school. Medical Education. 1986;20(4):267-73.
  30. Coles CE, Spooner D. Lifelong learning in clinical oncology editorial series: introduction and overview. Clinical Oncology. 2011;23(5):309-11.
  31. The Australasian College of Dermatologists. 2016. ACD e-Learning Portal. Australia: The Australasian College of Dermatologists.
  32. Australian Institute of Health and Welfare. AIoHaWC. Cancer in Australia: an overview, 2014. . Cancer series no 78 Cat no CAN 75 2014.
  33. Dolev JC, O’Sullivan P, Berger T. The eDerm online curriculum: a randomized study of effective skin cancer teaching to medical students. Journal of the American Academy of Dermatology. 2011;65(6):e165-e71.
  34. Back AL, Arnold RM, Tulsky JA, Baile WF, Fryer-Edwards KA. Teaching Communication Skills to Medical Oncology Fellows. Journal of Clinical Oncology. 2003;21(12):2433-6.
  35. Haidet P, O’Malley KJ, Richards B. An Initial Experience with “Team Learning” in Medical Education. Academic Medicine. 2002;77(1):40-4.
  36. Aspegren K. BEME Guide No. 2: Teaching and learning communication skills in medicine-a review with quality grading of articles. Medical teacher. 1999;21(6):563-70.
  37. Cave J, Woolf K, Dacre J, Potts HWW, Jones A. Medical student teaching in the UK: how well are newly qualified doctors prepared for their role caring for patients with cancer in hospital? British journal of cancer. 2007;97(4):472-8.
  38. Dennis KEB, Duncan G. Radiation oncology in undergraduate medical education: a literature review. International Journal of Radiation Oncology* Biology* Physics. 2010;76(3):649-55.
  39. Koczwara B, Tattersall MHN, Barton MB, Coventry BJ. Achieving equal standards in medical student education: is a national exit examination the answer? Medical journal of Australia. 2005;182(5):228.
  40. Lawson-Smith C. Achieving equal standards in medical student education: is a national exit examination the answer? The Medical journal of Australia. 2005;183(3):167.
  41. Dornan T, Hadfield J, Brown M, Boshuizen H, Scherpbier A. How can medical students learn in a self‐directed way in the clinical environment? Design‐based research. Medical education. 2005;39(4):356-64.
  42. Norman GR, Vleuten C, Newble D. (2002). International handbook of research in medical education. Boston: Kluwer Academic.
  43. Komatsu H, Yagasaki K. Are we ready for personalized cancer risk management? The view from breast-care providers. International Journal of Nursing Practice 2014; 20(1): 39-45.
  44. Di Prospero LS, Seminsky M, Honeyford J, et al. Psychosocial issues following a positive result of genetic testing for BRCA1 and BRCA2 mutations: Findings from a focus group and a needs-assessment survey. Cmaj 2001; 164(7): 1005-9.
  45. Doherty GMW, L.W. Current Diagnosis & Treatment: Surgery (14th ed.). New York: McGraw-Hill Medical; 2015.
  46. Fashoyin-Aje L, Sanghavi K, Bjornard K, Bodurtha J. Integrating genetic and genomic information into effective cancer care in diverse populations. Annals of Oncology 2013; 24 Suppl 7: vii48-54.
Categories
Original Research Articles

General practitioner awareness of pharmacogenomic testing and drug metabolism activity status amongst the Black-African population in the Greater Western Sydney region

Background:  Individuals  of  black-African  background  have  a high variability in drug metabolising enzyme polymorphisms. Consequently, unless these patients are tested for these polymorphisms, it becomes difficult to predict which patients may have a sub-therapeutic response to medications (such as anti- depressants) or experience an adverse drug reaction. Given the increasing population of black-Africans in Australia, GPs are on the front line of this issue, especially in Greater Western Sydney (GWS) – one of the country’s rapidly increasing populations due to migration. Aim: To ascertain the awareness of GPs regarding drug metabolising enzyme polymorphisms in the black-African population and pharmacogenomic testing in the GWS community. Methods:  A  descriptive,  cross-sectional  study  was  conducted in GWS by analysing GP responses to a questionnaire consisting of closed and open-ended questions. Results: A total of 46 GPs completed the questionnaire. It was found that 79.1% and 79.5% of respondents were unaware of: the high variability in drug metabolism enzyme activity in the black-African population and pharmacogenomic testing (respectively). No respondents had ever utilised pharmacogenomic testing. Only a small proportion of GPs “always” considered a patient’s genetic factors (13.9%) and enzyme metaboliser status (11.1%) in clinical practice. Preferred education media for further information included written material, direct information from other health professionals (such as pharmacists) and verbal teaching sessions. Conclusion: There was a low level of awareness of enzyme metaboliser status and pharmacogenomic testing amongst GPs in GWS. A future recommendation to ameliorate this includes further education provision through a variety of media noted in the study.

v6_i1_a21a

Introduction

Depression accounts for 13% of Australia’s total disease burden, making it an important health issue in the current context. [1] General Practitioners (GPs) are usually the first point of contact for patients seeking help for depression. [2,3] Antidepressant prescription is the most common treatment form for depression in Australia with GPs prescribing an antidepressant to treat up to 40% of all psychological problems. [2] This makes GP awareness of possible treatment resistance or adverse drug reactions (ADRs) to these medications vital.

Binder et al. [4] described pharmacogenomics as “the use of genome- wide approaches to elucidate individual differences in the outcome of drug therapy”. Detecting clinically relevant polymorphisms in genetic expression can potentially be used to identify susceptibility to ADRs. [4] This would foster the application of personalised medicine by  encouraging  an  inter-individual  approach  to  medication  and dose prescriptions based on an individual’s predicted response to medications. [4,5]

Human DNA contains genes that code for 57 cytochrome (CYP) P450 isoenzymes; these are a clinically important family of hepatic and gastrointestinal isoenzymes responsible for the metabolism of over 70% of clinically prescribed drugs. [5-10] The CYP family of enzymes are susceptible to polymorphisms as a result of genetic variations, influenced by factors such as ethnicity. [6,5,10] Research has shown that polymorphisms in certain CYP drug metabolising enzymes can result in phenotypes that class individuals as “ultrarapid metabolisers (UMs), extensive metabolisers (EMs), intermediate metabolisers (IMs) and poor metabolisers (PMs).”[6,10] These categories are clinically important as they determine whether or not a drug stays within the therapeutic range. Individuals with PM status may be susceptible to experiencing ADRs as a result of toxicity, and conversely, those with UM status may not receive a therapeutic effect. [5,6,10,11]

When considering the metabolism of antidepressants, the highly polymorphic CYP enzymes: CYP2C19 and CYP2D6 are known to be involved. [5,10,12] A study by Xie et al. [13] has shown that for the CYP2D6 enzyme alone, allelic variations induce polymorphisms that result in a PM phenotype of “~1%” in Asian populations, “0-5%” among Caucasians and a variation of between “0-19%” in black- African populations. This large disparity of polymorphism phenotypes was reproduced in a recent study, which also showed that the variation is not exclusive to the CYP2D6 enzyme. [6] It has been reported that the incidence of ADRs among PMs treated with drugs such as antidepressants is 44% compared to 21% in other patients. [5,14] Consequently, increased costs have been associated with the management of UM or PM patients. [5]

The black-African population in Australia and specifically Sydney (where GWS is one of the fastest growing regions) continues to rise through migration and humanitarian programs. [15-18] Almost 30% of Africans settling in Australia in the decade leading to the year 2007 did so under humanitarian programs including under refugee status. [15-17] As refugees are at a higher risk of having mental health problems including depression  due  to  their  traumatic  histories  and  post-migratory difficulties, GPs in GWS face increased clinical interactions with  black-Africans  at  risk  of  depression.  [19,20]  Considering  the high  variability of enzyme   polymorphisms   in   this   population, pharmacogenomic testing may play a role in the primary care of these patients. We therefore conducted a study to assess GP awareness of pharmacogenomic testing and the differences in enzyme metaboliser status (drug metabolism phenotypes). We also investigated the GP preferences of media for future education on these topics.

Methodology

Study Design and Setting

This is a descriptive, cross-sectional study. Ethics approval was granted by the Human Research Ethics Committee.

Considering GWS is the fastest growing region in Sydney, we focussed on particular suburbs in GWS (Blacktown, Parramatta and Holroyd Local Government Areas). [17-20] Using geographical cluster sampling, a list of GP practices were identified with the aim of recruiting 50 participants.

Study tool

Data was collected using a questionnaire validated by university supervisors and designed to elicit the level of understanding and awareness among GPs. The main themes of the questionnaire involved: questions regarding basic demographic information; questions aimed at determining the level of GP awareness regarding differences in drug metabolising phenotypes and pharmacogenomic testing; and open- ended questions eliciting the preferred methods of education with respect to pharmacogenomic testing.

Data Collection

We invited 194 GPs between April and May 2014 to participate in the study. The questionnaire and participant information sheet were either given to the practice managers or to the GPs in person. Questionnaires were collected in person within the following two weeks.

Data Analysis

Data was analysed using SPSS (version 22, IBM Australia). Descriptive statistics were used to summarise findings, with p-values calculated using Chi-square analysis (with Yates correction) to compare two sets of data. A p-value of <0.05 indicated statistical significance.

Results

The overall response rate was 23.7% (46/194). Our respondents included: 27 females and 19 males. The mean number of years of experience in general practice was 13.9 and most GPs (93.4%, 43/46) had received some form of training in antidepressant prescription in the last 5 years. The number of patients of black-African background seen in the last 6 months ranged from 0 to greater than 100. Only

26.1% (12/46) of GPs reported no consultations with a patient of black- African background within this timeframe. Of the 73.9% (34/46) of GPs who had seen at least one patient from this cohort, 55.9% (19/34) had treated at least one patient for depression with antidepressants.

GPs experience of ADRs in patients of black-African background treated for depression

From 46 participants, 19 had treated a patient of black-African background with antidepressants, 18/19 reported having identified at least one ADR (Figure 1).

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GP awareness and consideration of drug metabolism activity status and genetic factors

Awareness amongst GPs of the different drug metabolism activity phenotypes in black-Africans was low with 79.1% (34/43) being unaware. Patients’ genetic factors and enzyme metaboliser status were “always” considered by only 13.9% (5/36) and 11.1% (4/36) of GPs, respectively. There was no statistically significant difference regarding awareness between GPs who had treated black-African patients and those who had not (21.1% vs 13.3% respectively, p=0.89).

GP awareness and use of pharmacogenomic testing

The awareness of methods for testing a patient’s key drug metabolising enzymes, also known  as  pharmacogenomic testing, was extremely low with 79.5% (35/44) of GPs being unaware of the testing methods available in Australia. Of the 20.5% of GPs (9/44) who were aware, none had utilised pharmacogenomic testing for their black-African patients. These nine GPs then nominated factors that would influence their utilisation of pharmacogenomic testing on these individuals. Three main categories of influence emerged (Table 1). When specifically asked whether they would be more inclined to utilise pharmacogenomic testing on black-African patients who had previously experienced ADRs, 88.9% (8/9) GPs stated that they would be more inclined.

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Preferred education media

GPs that were aware of pharmacogenomic testing were asked, through an open-ended question, how they obtained information regarding these  methods.  Three  main  categories  were  identified  based  on their responses (Table 2). All GPs were then asked to note down their preferred medium of education for pharmacogenomic testing (Table 3). Multiple responses were allowed.

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Discussion

This study showed that there is a low level of awareness regarding pharmacogenomic testing and the differences in drug metabolism phenotypes among GPs. Additionally, we identified the preferred education media for providing information to GPs (Table 3). Awareness of pharmacogenomic testing and of the differences in drug enzyme metaboliser status (phenotype) could be valuable in the clinical setting. Improved patient outcomes have been noted when doctors are able to personalise management based on information from pharmacogenomic testing,[21] with Hall-Flavin et al. [21] noting significantly improved baseline depression scores amongst patients with depression whose doctors were provided with information on pharmacogenomics.

A previous study reported that a high proportion (97.6%) of physicians agreed that differences in genetic factors play a major role in drug responses.  [22]  Whilst  it  is  arguable  that  knowledge  of  genetic factors holistically playing a role in drug response may be universal, our study specifically focussed on the knowledge of differences in enzyme metaboliser status. It was found that 79.1% of GPs (34/43) were unaware, with only a small number of GPs “always” considering enzyme metaboliser status (11.1%) in their management. Given the aforementioned  importance  of  genetic  factors  and  the  potential to reduce ADRs using personalised medicine, this is an area for improvement.

When considering pharmacogenomic testing, we found 79.5% (35/44) of GPs to be unaware of testing methods. No GP had ever utilised pharmacogenomic testing, this low rate of utilisation is also reported previously in other several studies. [22-24] A lack of utilisation and awareness arguably forms a barrier against the effective incorporation of personalised medicine in the primary care setting. These low figures represent a lack of education regarding pharmacogenomics and its clinical applications. This is an issue that has been recognised since the arrival of these testing methods. [25] McKinnon et al. [25] highlighted that this lack of education across healthcare professionals is significant enough to be considered a “barrier to the widespread uptake of pharmacogenomics”. To ameliorate the situation, the International Society of Pharmacogenomics has issued recommendations in 2005 for  pharmacogenomics  to  be  incorporated  into  medical  curricula. [26]  Another  contributing  factor  to  the  low  utilisation  of  testing could include the lack of subsidised tests available through Medicare. Currently, pathology labs do provide pharmacogenomic testing (such as Douglas Hanley Moir and Healthscope), however this is largely done so through the patient’s expenses as only two methods are subsidised by Medicare. [23,27,28]

Amongst those aware of pharmacogenomic testing, eight out of nine GPs answered that they would be more likely to utilise pharmacogenomic testing in black-African patients who had previously experienced ADRs; this is consistent with findings noted by van Puijenbroek et al. [29]. Among these GPs, factors that were noted to be potential influences in their utilisation of testing included: patient factors such as compliance and the reliability of the test, and, factors affecting the clinical picture (as described in Table 1). This is consistent with findings by studies that have also identified cost and a patient’s individual response to drugs as influential factors in a physician’s decision making. [29,30]

Considering that the majority of information regarding enzyme metabolism and pharmacogenomic testing was published in pharmacological journals,[6,8-14,30-32] much of this knowledge may not have been passed on to GPs. In order to understand the preferred media of information for GPs, we posed open-ended questions and discovered that the majority of GPs who answered the question (32/39), would prefer information in the form of writing (Table 3). This could be either in the form of online sources (such as guidelines, summaries, the National Prescribing Service or the Monthly Index of Medical Specialities) or peer reviewed journal articles. Current literature also reflects this preference for GPs to gain education regarding pharmacogenomics through journal articles. [22] The other preferred medium of education was through verbal teachings, peer discussions and presentations (Table 3), with there being specific interest in information being disseminated by clinical pathology laboratories; this is also reflected in the literature. [22,29]

Strengths and limitations

Small sample size is a limitation of this study with possible contributing factors including: the short amount of time allowed for data collection and the low response rate due to GP time constraints. Strengths of the study include the use of a validated questionnaire catered to our target population and open-ended questions which gave us further insight into GP preferences.

Implications and future research

Currently, anti-coagulants provide an example of the clinical applications of considering enzyme polymorphisms in patient management. [33,34] Warfarin is a particular example where variability in INR has been associated with enzyme polymorphisms, leading to the utilisation of dosage algorithms to optimise clinical outcomes. [34] Similarly, when using antidepressants, pharmacogenomic testing could play a role in clinical decision making with Samer et al. [5] suggesting dose reductions and serum monitoring for those with known PM status. However, as identified in our study, there is an overall lack of awareness regarding the differences in enzyme metaboliser status and the methods available for pharmacogenomic testing.

Future studies should focus on the clinical practicality of utilising these tests. Additionally, future studies should determine the effectiveness of the identified GP preferred modalities of education in raising awareness.

Conclusion

There is a low awareness among GPs regarding both the differences in enzyme metaboliser status in the black-African community, and the methods of pharmacogenomic testing.

To optimise clinical outcomes in black-African patients with depression, it  may  be  useful  to  inform  GPs  of  the  availability  and  application of pharmacogenomic testing. We have highlighted the preferred education modalities through which this may be possible.

Acknowledgements

We would like to acknowledge and thank Dr. Irina Piatkov for her support as a supervisor during this project.

Conflict of interest

None declared.

Correspondence

Y Joshi: 17239266@student.uws.edu.au

References

[1] Australian Institute of Health and Welfare. The burden of disease and injury in Australia 2003  [Internet].  2007  [cited  2014  April  25].  Available  from:  http://www.aihw.gov.au/ publication-detail/?id=6442467990

[2] Charles J, Britt H, Fahridin S, Miller G. Mental health in general practice. Aust Fam Physician. 2007;36(3):200-1.

[3] Pierce D, Gunn J. Depression in general practice: consultation duration and problem solving therapy. Aust Fam Physician. 2011;40(5):334-6.

[4]  Binder  EB,  Holsboer  F.  Pharmacogenomics  and  antidepressant  drugs.  Ann  Med. 2006;38(2):82-94.

[5] Samer CF, Lorenzini KI, Rollason V, Daali Y, Desmeules JA. Applications of CYP450 testing in the clinical setting. Mol Diagn Ther. 2013;17(3):165-84.

[6]  Alessandrini  M,  Asfaha  S,  Dodgen  MT,  Warnich  L,  Pepper  MS. Cytochrome  P450 pharmacogenetics in African populations. Drug Metab Rev. 2013;45(2):253-7.

[7] Yang X, Zhang B, Molony C, Chudin E, Hao K, Zhu J et al. Systematic genetic and genomic analysis of cytochrome P450 enzyme activities in human liver. Genome Res. 2010;20(8):1020-36.

[8] Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities and impact of genetic variation. Pharmacol Therapeut. 2013;138(1):103-41.

[9]  Guengerich  FP.  Cytochrome  P450  and  chemical  toxicology.  Chem  Res  Toxicol. 2008;21(1):70-83.

[10] Ingelman-Sundberg M. Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J. 2005;5:6-13.

[11] Zhou S. Polymorphism of human cytochrome P450 2D6 and its clinical significance. Clin Pharmacokinet. 2009;48(11):689-723.

[12] Li-Wan-Po A, Girard T, Farndon P, Cooley C, Lithgow J. Pharmacogenetics of CYP2C19: functional and clinical implications of a new variant CYP2C19*17. Br J Clin Pharmacol. 2010;69(3):222-30.

[13] Xie HG, Kim RB, Wood AJJ, Stein CM. Molecular Basis of ethnic differences in drug disposition and response. Ann Rev Pharmacol Toxicol. 2001;41:815-50.

[14] Chen S, Chou WH, Blouin RA, Mao Z, Humphries LL, Meek QC et al. The cytochrome P450  2D6  (CYP2D6)  enzyme  polymorphism:  screening  costs  and  influence on  clinical outcomes in psychiatry. Clin Pharmacol Ther. 1996;60(5):522–34.

[15]  Hugo  G.  Migration  between  Africa  and  Australia:  a  demographic  perspective  – Background paper for African Australians: A review of human rights and social inclusion issues. Australian Human Rights Commission [Internet]. 2009 Dec [cited 2014 April 26]. Available  from:  https://www.humanrights.gov.au/sites/default/files/content/Africanaus/papers/Africanaus_paper_hugo.pdf

[16]  Joint  Standing  Committee  on  Foreign  Affairs,  Defence  and  Trade.  Inquiry  into Australia’s relationship with the countries of Africa [Internet]. 2011 [cited 2014 April 26]. Available  from:  http://www.aph.gov.au/Parliamentary_Business/Committees/House_of_Representatives_Committees?url=jfadt/africa%2009/report.htm

[17] Census 2006 – People born in Africa [Internet]. Australian Bureau of Statistics; 2008 August 20 [updated 2009 April 14; cited 2014 April 26]. Available from: http://www.abs.gov.au/AUSSTATS/abs@.nsf/Lookup/3416.0Main+Features32008

[18]    Greater    Western    Sydney    Economic    Development    Board.    Some    national transport  and  freight  infrastructure  priorities  for  Greater  Western  Sydney  [Internet]. Infrastructure    Australia;    2008    [cited    April    25    2014].    Available    from:    http:// w w w. i n fras tru ctu r eau s tral i a. g o v. au /p u b l i c_su b mi ssi o ns/p u b l i sh ed /fi l es/368_ greaterwesternsydneyeconomicdevelopmentboard_SUB.pdf

[19] Furler J, Kokanovic R, Dowrick C, Newton D, Gunn J, May C. Managing depression among ethnic communities: a qualitative study. Ann Fam Med. 2010;8:231-6.

[20] Robjant K, Hassan R, Katona C. Mental health implications of detaining asylum seekers: systematic review. Br J Psychiatry. 2009;194:306-12.

[21] Hall-Flavin DK, Winner JG, Allen JD, Carhart JM, Proctor B, Snyder KA et al. Utility of integrated pharmacogenomic testing to support the treatment of major depressive disorder in a psychiatric outpatient setting. Pharmacogenet Genomics. 2013;23(10):535- 48.

[22] Stanek EJ, Sanders CL, Taber KA, Khalid M, Patel A, Verbrugge RR et al. Adoption of pharmacogenomics testing by US physicians: results of a nationwide survey. Clin Pharmacol Ther. 2012;91(3):450-8.

[23] Sheffield LJ, Phillimore HE. Clinical use of pharmacogenomics tests in 2009. Clin Biochem Rev. 2009;30(2):55-65.

[24] Corkindale D, Ward H, McKinnon R. Low adoption of pharmacogenetic testing: an exploration and explanation of the reasons in Australia. Pers Med. 2007;4(2):191-9.

[25]  McKinnon  R,  Ward  M,  Sorich  M.  A  critical  analysis  of  barriers  to  the  clinical implementation of pharmacogenomics. Ther Clin Risk Manag. 2007;3(5):751-9.

[26]  Gurwitz  D,  Lunshof  J,  Dedoussis  G,  Flordellis  C,  Fuhr  U,  Kirchheiner  J  et  al. Pharmacogenomics      education:      International      Society      of      Pharmacogenomics recommendations for medical, pharmaceutical, and health schools deans of education. Pharmacogenomics J. 2005;5(4):221-5.

[27]  Pharmacogenomics  [Internet].  Healthscope  Pathology;  2014  [cited  2014  October 22]    Available    from:    http://www.healthscopepathology.com.au/index.php/advanced pathology/pharmacogenomics/

[28]  Overview  of  Pharmacogenomic  testing.  Douglas  Hanley  Moir  Pathology;  2013 [cited  2014  October  22].  Available  from:  http://www.dhm.com.au/media/21900626/pharmacogenomics_brochure_2013_web.pdf

[29] van Puijenbroek E, Conemans J, van Groostheest K. Spontaneous ADR reports as a trigger for pharmacogenetic research: a prospective observational study in the Netherlands. Drug Saf. 2009;32(3):225-64.

[30]  Rogausch  A,  Prause  D,  Schallenberg  A,  Brockmoller  J,  Himmel  W.  Patients’  and physicians’ perspectives on pharmacogenetic testing. Pharmacogenomics. 2006;7(1):49- 59.

[31] Akilillu E, Persson I, Bertilsson L, Johansson I, Rodrigues F, Ingelman-Sundberg M. Frequent distribution of ultrarapid metabolizers of debrisoquine in Ethopian population carrying duplicated and multiduplicated functional CYP2D6 alleles. J Pharmacol Exp Ther. 1996;278(1):441-6.

[32] Bradford LD. CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics. 2002;3:229-43.

[33] Cresci S, Depta JP, Lenzini PA, Li Ay, Lanfear DE, Province MA et al. Cytochrome p450 gene variants, race, and mortality among clopidogrel-treated patients after acute myocardial infarction. Circ Cardiovasc Genet. 2014 7(3):277-86.

[34] Becquemont L. Evidence for a pharmacogenetic adapted dose of oral anticoagulant in routine medical practice. Eur J Clin Pharmacol. 2008 64(10):953-60