Clinical pharmacology is a medical specialty concerned with the research, teaching and clinical application of what the human body does to drugs and what drugs do to humans. The knowledge and correct application of drug therapies is a core responsibility of every physician and crosses every disease and organ group. At a population level, Canada along with every other developed country, has noted that drugs form the fastest growing component of health care budgets. This means that there is tremendous pressure to ensure that medicines are provided in the most judicious (effective, safe and cost-effective) manner to optimize health. More recently, medication safety problems have been recognized as the most prominent single source of internal medicine patient adverse events and as a common source of disciplinary action against physicians. At an international, national and local level, it has been noted that trainees receive inadequate training in clinical pharmacology and therapeutics. In addition, overdose and drug use disorders are common and require toxicology knowledge and expertise.

Clinical pharmacologists with combined clinical expertise, critical appraisal abilities, knowledge of drug action and familiarity with regulatory and reimbursement policies, influence healthcare at all levels (policy, provider and patient) and are in exceedingly short supply.

It is imperative that each practicing medicine specialist has a basic competence in safe prescribing and evidence-based therapeutics.

Every physician, no matter what specialty, must learn to prescribe competently, which means choosing medications based on an accurate diagnosis, indication, prior therapies, applying high levels of evidence for effectiveness, safety and cost-effectiveness. In addition, prescribing competence requires ongoing monitoring for benefit and harm, expertise in patient communications, knowledge of the regulatory and formulary environment, and an ability to de-prescribe appropriately.

Institute for Safe Medical Practices

Clinical Pharmacology and Toxicology knowledge and Prescribing competence, especially in training and early years of practice, correlates with fewer medication errors, better licensing exam results, fewer professional disciplinary complaints, and improved sustainability of health care.

Physicians and the Pharmaceutical Industry: Interests and Conflicting Interests

References:

• College of Physicians and Surgeons of Ontario. PRESCRIBING DRUGS. December 2019.
• World Health Organization. MEDICATION WITHOUT HARM. 2022.

A few helpful pharmacology e-textbooks:

• Goodman & Gilman’s: The Pharmacological Basis of Therapeutics, 14e | AccessMedicine | McGraw Hill Medical (mhmedical.com)
• Basic & Clinical Pharmacology, 15e | AccessMedicine | McGraw Hill Medical (mhmedical.com)
• The Washington Manual of Medical Therapeutics

Links to Dr. Mitch Levine’s pharmacology talks:
*disclaimer: you need to have, and use, a Medportal login to access the links below

• Natural Health Products | Session · medportal
• Pharmacokinetics | Session · medportal
• Pharmacokinetics Part 2 | Session · medportal
• Clinical Pharmacology | Session · medportal

Canadians do not have universally funded Pharmacare. They do, however, in most provinces, have income-adjusted access to a formulary of approximately 4000 medications. Health Canada’s federal drug regulation system works similarly to the FDA in the USA and EMEA in Europe. Manufacturers bring drugs for approval based primarily on efficacy while demonstrating acceptable safety. Promising medications for serious conditions where there is a high need for better therapies, are sometimes granted Notice of Compliance with Conditions (NoCC) where additional evidence must be gathered to confirm initial impressions of effiacy and safety. This is an important distinction from full Notice of Compliance (NoC) as NoCC medications frequently do not turn out to be safe and effective.

Once cleared by Health Canada with NoC, medications are usually submitted to the Common Drug Review at CADTH (Canadian Agency for Drugs and Technology in Health) for recommendations regarding funding through public formularies in the provinces and territories. This requires an additional and more rigorous standard of evidence based on societal value, systematic review of the evidence with economic analysis of cost-effectiveness, and burden of illness.

The recommendations from the expert advisory committees based on the above review, are then considered by the individual provinces/territories and a formulary designation made. In Ontario, this is managed by the Ontario Public Drug Benefit Program. This program covers, seniors 65 years and older, children and youth 25 years and younger, those on disability or social assistance, and those with extreme drug expenditures relative to household income.

Drug Product Database online query (canada.ca)

Formulary Search (gov.on.ca)

The Drug Review and Approval Process in Canada

CADTH. Reimbursement Reviews. 2020.

CMPA. Medication Safety. 2021.

It has been shown that poor training in medical school  and poor communication skills with patients, predict medicolegal trouble in practice. Trainees are referred to earlier chapters on Advice on Prescribing from the CPSO. Careful review of advice from the Canadian Medical Protective Association (CMPA), is also crucial to safe and successful practice.

Health Advocacy is a key role and competency for physicians in Canada, so much so that it is one of the main CanMEDS competencies.

In our discipline, typical patient advocacy roles include:

a) completing forms regarding restricted access to expensive non-formulary medications for patients meeting criteria or where there is no other option

b) continually working with patients to reduce and discontinue their exposure to harmful medications including alcohol, tobacco, cocaine and similar stimulants, high dose opioids, etc.

c) recognizing and remediating vulnerable situations where patients are at risk of lethal overdoses or poisonings.

d) participating in high quality research with patients that will address important medication-related questions.

e) discouraging use of expensive, supplements and natural health products which lack adequate evidence of effectiveness and safety, and are not regulated in terms of contamination.

CMPA. Participating in Health Advocacy.

APPROPRIATENESS OF PRESCRIBING QUESTIONNAIRE (APEQ) DOMAINS

Holbrook, AM et al.

(More specific criteria are developed for each drug/drug family)

1. Indication – appropriate diagnosis?
2. Indication – appropriate prior therapy?
3. Benefit/Harm – optimal Drug Choice based on RCT Evidence?
4. Dosage – correct?
5. Directions – correct (where relevant)?
6. Clinically important drug-drug interactions?
7. Clinically important drug-disease interactions (contraindications)?
8. Unnecessary therapeutic duplication?
9. Duration – acceptable duration to next physician assessment?
10. Cost-effectiveness – relative to other drugs or treatments in the same therapeutic class?

Reference:

• A comprehensive appropriateness of prescribing questionnaire was validated by nominal consensus group

List curated by CPT specialists, internal medicine and pediatric specialists, regularly updated. This is modelled after the long-standing World Health Organization concept of an essential drugs list for poor countries, however our list has been modified to be relevant for Canadian practice. Most physicians will prescribe most frequently a core list of approximately 50-80 medications throughout their career. Our Essential Drugs List deliberately attempts to influence what that list should include.

Holbrook A. McMaster Essential/Core Drugs List for Medical Students. MacSphere, McMaster University: Medicine Publications collection; Hamilton ON, 2022. http://hdl.handle.net/11375/27291

This product of a previous eCampusOntario grant provides a curated list of key e-curriculum resources that have been evaluated by clinical, research, usability and e-learning experts. Most resources are international (for example, the Australian National Prescribing Curriculum (NPC) is excellent), therefore Canadian preambles are provided for areas of translation.

General Preamble

Our own work with Canadian medical students shows that many lack basic clinical pharmacology and therapeutics knowledge, and prescribing skills as schools struggle to meet all of their required curricula objectives.^{1, 2} Expertise in this broad-based specialty is scarce, and most medical schools no longer have dedicated clinical pharmacology courses. However, for the first time, the Medical Council of Canada has recently launched specific Prescribing Practices objectives that schools must cover.³

Safe prescribing is a complex activity requiring detailed knowledge of dozens of drug families, accurate patient diagnosis and individual risk assessment, excellent communication and interprofessional collaboration skills, and professionalism. More than 700 million prescriptions are written annually in Canada for drugs from approximately 1100 therapeutic groups.⁴ Medication errors are common, usually go unrecognized and can pose a serious patient safety hazard.^{2, 5-8} Medical students and residents are especially vulnerable, with prescribing errors on 7-10% of their prescriptions.⁵

Competent prescribing and medication management is even more essential as years go on, given the dozens of new medications introduced each year, primarily high-risk medications and very expensive medications, increasing numbers of patients with extreme polypharmacy, lethal problems with drug overdose and poisoning, and poor adherence with effective medications.

1. Royal College of Physicians and Surgeons of Canada: The Prescribing Safely Canada Physician Prescribing Competencies – Executive Summary
2. The Prescribing Safely Canada Physician Prescribing Competencies
3. College of Physicians and Surgeons of Ontario’s Advice to the Profession on Prescribing Drugs CPSO – Prescribing Drugs CPSO – Advice to the Profession: Prescribing DrugsAdditional, valuable documents for learners on the prescribing competence topic include:
4. The World Health Organization’s Guide to Good Prescribing: A Practical Manual – useful not specifically for the patient examples or specific drug examples, but for the recommended process of prescribing.
5. The Essential Drugs List for McMaster Medical Students: http://hdl.handle.net/ 11375/27291 – useful for specific drug and drug family examples that should become familiar to every medical trainee
6. The Institute for Safe Medication Practices Canada (ISMP Canada)’s resources including i) DO NOT USE List of Dangerous Abbreviations Symbols and Dose Designations – abbreviations, symbols, and dose designations reported as being frequently misinterpreted and contributing to harmful medication errors, and ii) List of High-Alert Drugs – medications with an increased risk of causing significant patient harm when they are used inappropriately, including lack of indication, wrong dose, contraindications, etc. ^{9, 10}
7. Health Canada’s Drug Product Database provides access to the full product monographs from all manufacturers of medications approved for use in Canada. Product monographs are the ‘bottom line’ on your medico-legal responsibilities. In other words, if a medication does not have an official indication for the disease or condition that you are treating or does not have clear, supportive randomized trial evidence, and you cannot justify that you have tried all other reasonable avenues and the patient was aware of and agreed with your rationale to prescribe the drug, then if a major adverse event related to the drug occurs, you will be at risk of successful legal and disciplinary challenge.
8. Drug formulary and coverage is an essential consideration when prescribing any medication. Formularies in Canada are based on the highest quality cost-effectiveness information and evaluation.¹¹ Each province and territory has their own that can be accessed individually. For Ontario, this can be accessed via: https://www.formulary.health.gov.on.ca/formulary/.
9. Conflicts of Interest – Physicians must avoid conflicts of interest to ensure that their professional priorities remain patients and advancing healthcare, particularly when dealing with the pharmaceutical and device industry.¹²

References:

1. Holbrook A, Liu JT, Rieder M, Gibson M, Levine M, Foster G, et al. Prescribing competency assessment for Canadian medical students: a pilot evaluation. Can Med Educ J. 2019;10(1):e103-e10. ↑
2. Liu J, Wong S, Foster G, Holbrook A. Prescribing Competency of Medical Students: National Survey of Medical Education Leaders. J Popul Ther Clin Pharmacol. 2018;25(1):e18-e24. ↑
3. MCC. Prescribing Practices Ottawa, Canada: MCC; 2022 [Available from: https://mcc.ca/objectives/expert/key/125/]. ↑
4. Canada Health Infoway. Current prescribing and dispensing landscape in Canada: CHI; 2017 [Available from: https://infocentral.infoway-inforoute.ca/en/resources/docs/medmgmt/1778-report-2017-current-prescribing-and-dispensing-landscape-in-canada. Accessed on 23 Apr 2019]. ↑
5. Dornan T, Ashcroft D, Heathfield H, Lewis P, Miles J, Taylor D, et al. An in-depth investigation into causes of prescribing errors by foundation trainees in relation to their medical education: EQUIP study. London: General Medical Council. 2009:1-215. ↑
6. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998;279(15):1200-5. ↑
7. Ryan C DP, Francis J, Johnston M, Ker J, Lee AJ, et al. The Prevalence of Prescribing Errors amongst Junior Doctors in Scotland. Basic and Clinical Pharmacology and Toxicology. Basic and Clinical Pharmacology and Toxicology. 2011;109(35). ↑
8. Young H. Lack of pharmacological training causes overuse and misuse of drugs. CMAJ. 2008;178(3):276. ↑
9. ISMP. Do Not Use: Dangerous Abbreviations, Symbols and Dose Designations. Toronto, ON: ISMP 2018 [Available from: https://www.ismp-canada.org/download/ISMPCanadaListOfDangerousAbbreviations.pdf]. ↑
10. ISMP. ISMP List of High-Alert Medications in Acute Care Settings. Toronto, ON: ISMP; 2018 [Available from: https://www.ismp.org/sites/default/files/attachments/2018-08/highAlert2018-Acute-Final.pdf]. ↑
11. CADTH. Guidelines for the Economic Evaluation of Health Technologies: Canada. Ottawa, ON: CADTH; 2017. ↑
12. CPSO. Physicians’ Relationships with Industry: Practice, Education and Research. Toronto, ON: CPSO; 2014 [Available from: https://www.cpso.on.ca/Physicians/Policies-Guidance/Policies/Physicians-Relationships-with-Industry-Practice]. ↑

Holbrook A, Patel D, Yoo L. Introductory Preambles to Clinical Pharmacology and Toxicology eCurriculum Resources for Canadian Medical Students [MacSphere]. McMaster University, Department of Medicine: Hamilton, Ontario; 2022. Available from http://hdl.handle.net/11375/27381

Links to Australian National Prescribing Curriculum course with Canadian adaptation (eg, Choosing Wisely Canada), and Vanessa’s Law reporting obligations, with interpretation preambles for medical students.

Understanding Medication Safety
Preamble:

Dr. Spellberg’s video recording for grand rounds:
Short Course Antibiotic Therapy. Youtube [internet]. Los Angeles County, University of Southern California; October 13 2022 [cited October 20 2022]. Available from Short Course Antibiotic Therapy – YouTube.

Link to Dr. Spellberg’s antibiotics website: Shorter Is Better | mysite (bradspellberg.com)

Links to Australia NPC course, Canadian antibiogram data, and other Canadian resources

Australian NPC course: https://learn.nps.org.au/
Preamble:

Link to useful introduction on the importance of Drug Interactions to Adverse Drug Events:

• Preventable Adverse Drug Reactions

Link to e-textbook on poisonings and drug overdose:

• Poisoning & Drug Overdose, 8e | AccessMedicine | McGraw Hill Medical (mhmedical.com)

*disclaimer: you must have, and use, a Medportal login to access the link below

• Adverse Drug Reactions | Session · medportal
• Drug Interactions | Session · medportal
• Drug Metabolism | Session · medportal

Mandatory NPC modules for Transitions to Clerkship

Type 2 Diabetes: Initiating Treatment

Preamble: The case description and details about symptoms, vitals, history etc. are reasonable and should be understood by the Canadian learners.

Urinary Tract Infection
Preamble:

Postoperative Pain and Vomiting

Analgesia for Low Back Pain

Polypharmacy

Chronic obstructive pulmonary disease (COPD) exacerbation
Preamble: Important clarifications for Canadian medical students:

Hypertension

Prevention of Venous Thromboembolism

Child with Acute Otitis Media

Strongly suggested but not mandatory NPC Modules

• Antimicrobials: bacteremia (online course)
• Antimicrobials: surgical prophylaxis (online course)
• Antimicrobials: catheter-associated urinary tract infections (online course)
• Antimicrobials: community-acquired pneumonia (online course)
• Acute pulmonary edema (NPC module)
• Chronic heart failure (NPC module)Alcohol withdrawal delirium (NPC module)
• Lipid and CVD risk management (NPC)
• Delirium in an older person (NPC)
• Insomnia (NPC)
• H. pylori infection (NPC)
• Iron deficiency (NPC)
• Anticoagulation in atrial fibrillation (NPC)
• Management of acute coronary syndrome (NPC)
• Depression in adolescents (NPC)
• Acute mania in bipolar disorder (NPC)
• Preventing fractures: where to start with osteoporosis (NPC)

A suggested Medical Toxicology curriculum for medical students, has been suggested by a consensus group in the USA – see Table 1 in this publication.

Goldfine C, Lung D, Beauchamp G, O’Connor A, Stolbach A, Kao L, Judge B, Wax P, Patwari R, Kazzi Z. Consensus Development of a Core Content for a Standardized Medical Toxicology Curriculum for Medical Students. J Med Toxicol. 2022 Apr;18(2):139-144. doi: 10.1007/s13181-021-00874-z. Epub 2022 Jan 28. PMID: 35089533; PMCID: PMC8796743.

*disclaimer: you will need to have, and use, a Medportal login to access the links below

• Maternal Fetal Pharmacology | Session · medportal
• Toxicology | Session · medportal
• Drug Use in Renal Dysfunction | Session · medportal

Opioids and Non-opioids in the Management of Pain: Time for Change

Just say KNOW to drugs

We are developing a computerized prescription writing assessment tool that will allow much broader formative practice, assessment and feedback for medical students and residents to practice their therapeutics and  prescribing skills in a safe environment. This will be a form of ClinPharmTox simulation.

In the meantime, try this Prescription Writing simulation:

Click here to Download this exercise.

Reference:

• Khatami A, Holbrook A, Levinson AJ, Keshavjee K. Software Architecture for Automated Assessment of Prescription Writing [MacSphere]. McMaster University, Department of Medicine: Hamilton, Ontario; 2022. Available from http://hdl.handle.net/11375/27383

Concerns about prescribing competence are not isolated to North American medical graduates. The EQUIP study in England reviewed 124,260 medication orders finding an error rate as high as 10.3% amongst junior housestaff. In response to this study and a series of serious medication safety incidents, education leaders in clinical pharmacology and the British Pharmacological Society instituted the Prescribing Safety Assessment (PSA), an online exam that final year medical students must pass prior to their licensing exams. The full PSA consists of 60 questions and lasts for two hours, drawing on a large database of validated questions. Students participate in the PSA at the end of medical school a few months before their medical licensure examinations, and are encouraged to prepare using practice resources.(14) Approximately 53,000 students have completed the exam in the last five years, with very positive feedback on fairness and the helpfulness of the exam to their competence to practice. These students expressed appreciation for the initiative taken to address the prescription competency concerns, for increased their confidence when prescribing as a first year resident, and for making them aware of key prescribing resources such as formularies.

The Canadian PSA is a 30-question, 1 hour exam modified by Dr Holbrook from the British PSA. It has been tried consistently at McMaster University and sporadically at other Ontario medical schools over a 7-year period, with very good face validity. The exam is meant to be a formative assessment near the end of medical school as a measure of readiness for residency. Practice exams are made available for the Transitions to Clerkship period.

Recommendations to prepare for the PSA exam include:

1. Review the exam format, time available, open book resources allowed. There are 8 domains tested in the PSA.

Table 1: Prescribing Safety Assessment Question Domains

2. Since the Canadian PSA is open book, decide on resources that you want to use during the exam, for example, UptoDate, Lexicomp, RxTx, ODB formulary, etc.
3. Take time to do all of the practice exams allowed.

References:

• Holbrook A, Liu JT, Rieder M, Gibson M, Levine M, Foster G, et al. Prescribing competency assessment for Canadian medical students: a pilot evaluation. Canadian Medical Education Journal. 2019;10(1):e103-e110.
• Liu J, Wong S, Foster G, Holbrook A. Prescribing Competency of Medical Students: National Survey of Medical Education Leaders. Journal of Population Therapeutics and Clinical Pharmacology January 2018; doi 10.22374/1710-6222.25.1.2.