Evidence-Based Veterinary Medicine Notes

Introduction to Evidence-Based Veterinary Medicine

Learning Objectives

  • Explain and understand the steps of practicing evidence-based veterinary medicine.

  • Apply the principles of evidence-based veterinary medicine.

History of Evidence-Based Medicine (EBM)

  • Origins with people like Archie Cochrane, who realized during World War II that much of medicine used did not have sufficient evidence to justify its use.

  • Concept of EBM was further developed by David Sackett (1976) and others over the last decades.

What is Evidence-Based Medicine?

  • Evidence-based medicine (EBM): 'The conscientious, explicit, and judicious use of current best evidence in making decisions about individual patients' (Sackett et al., 1996).

  • Evidence-based veterinary medicine (EBVM): 'The use of current best evidence in making clinical decisions' (Cockcroft & Holmes, 2003).

  • EBVM practice: Integrating individual clinical expertise with the best available external clinical evidence from (systematic) research.

Veterinary and Human Medicine

  • Difference of EBVM compared to EBM:

    • Often no or limited scientific evidence is available in EBVM.

    • Often weaker evidence is used to make decisions in EBVM.

    • E.g., Expert opinion, personal experience, case reports.

  • Veterinarians handle often greater levels of uncertainty and risk.

Example: Ear Hematoma

  • Ear hematoma: collection of blood under the skin of the ear flap.

  • Often a result of trauma to the pinna or from the dog or cat scratching at the ear.

    • The itchy ear can result from ear mites, allergies, infections, or foreign matter in the ear canal.

  • Veterinarians generally recommend surgery to open and drain the hematoma and remove dead and degenerating clots and fibrin.

    • Sutures are used to tack the skin layers over the thin cartilage center to eliminate any space for more blood or serum to accumulate.

Example: Ear Hematoma - EBVM vs. Non-EBVM

  • No EBVM: Reasons for not considering alternatives to surgery:

    • This is the way I always do it.

    • This is the way it’s done at this clinic.

    • This way worked the last few times.

    • This way won’t do any harm.

    • This way is how ‘experts’ say it should be done.

    • This way is how the owner wants it done.

  • EBVM: Trying to get the best outcome for the patient by looking into alternative treatments for ear hematoma.

Steps for Practicing EBVM

  1. Formulate an answerable clinical question.

  2. Search for evidence to answer the question.

  3. Critically appraise the evidence.

  4. Apply the answer to your patient.

  5. Audit the outcome.

Reasons for Formulating a Clinical Question

  • Subconsciously, you are developing clinical questions about your case all the time.

  • Formulating your questions is helpful because:

    • This makes efficient use of your time.

    • This will allow targeted search of the literature/evidence using keywords.

    • This will allow you to make clear, objective conclusions.

  • Note that there are two kinds of clinical questions: background questions and foreground questions.

The Background Question

  • Comprises general knowledge of the field of interest.

    • General questions about conditions, syndromes, and patterns of disease, pathophysiology.

    • E.g., What causes ear hematoma?

  • Information can usually be sourced from textbooks or reviews.

  • You need a certain amount of background knowledge in order to formulate a specific structured foreground question that will help your particular patient.

Background Question – More Examples

  • How is Feline Immunodeficiency Virus transmitted?

  • What is the predominant erythrocyte morphology in lead poisoning?

The Foreground Question

  • The foreground question is much more specific.

    • E.g., Questions about therapies or diagnostic tests.

  • The foreground question helps you make decisions.

  • The question involves a comparison with something else.

  • Helpful to have a series of questions and narrow them down later to a refined clinical question.

Foreground Question – An Example

  • In dogs, what is the probability of clinical improvement with parenteral Solu-Medrol for acute traumatic myelopathy in the first 24 hours after injury when compared with a placebo?

Foreground Questions: PICO Approach

  • PICO: systematically clarifying the clinical question before searching the literature.

    • P = Population or patient group

    • I = Intervention

    • C = Comparison

    • O = Outcome

Clinical Problem: Renal Failure in Small Animals

  • Renal failure is defined as the inability of the kidneys to remove waste products from the blood.

  • The building up of toxins produces uremic poisoning.

  • You might have a 10-year old dog on the table in front of you, with renal failure. There is no way you can ‘know’ everything about renal failure in dogs.

  • However, a general knowledge of the topic, in combination with the problem faced by your specific patient, enables you to ask a structured ‘foreground’ question about treatment options.

Renal Failure in Small Animals – Background vs. Foreground

  • Background question:

    • What causes renal failure in small animals?

  • Foreground question:

    • In canine patients over 10 years of age with chronic renal failure, does treatment with an ACE inhibitor in addition to standard therapy lead to increased survival time and improved quality of life?

Population or Patient Group

  • Specify how you would define a group of patients similar to yours.

  • Categorize your patient group/population by:

    • Age, Sex, Breed

    • Environment (e.g., rural working cattle dog vs. dog in remote indigenous community vs. urban companion dog who lives indoors)

  • PICO – Patient group: canine patients older than 10 years with chronic renal failure (attributable to glomerular nephritis).

Intervention

  • Specify what you plan to do for the patient.

    • Therapy/prevention (e.g., medical, surgical, management).

    • Diagnostic test (e.g., ELISA, biopsy).

    • Exposure risk factor (e.g., potentially harmful or beneficial factor).

    • Patient risk factor (e.g., breed, age, sex).

  • PICO – Intervention: canine patients older than 10 years with chronic renal failure (attributable to glomerular nephritis) treated with an ACE inhibitor in addition to standard therapy.

Comparison

  • Specify one alternative choice.

    • Treatment: Treatment alternative is often the ‘standard treatment.’

    • Diagnosis: Diagnostic alternative is often the ‘old test.’

    • Risk factor: Risk factor exposure is often non-exposure to a risk factor.

  • PICO – Comparison: canine patients older than 10 years with chronic renal failure (attributable to glomerular nephritis) with on an ACE inhibitor in addition to standard therapy in comparison to the standard therapy of renal diet (low protein/PO4).

Outcome

  • Specify the results you plan to accomplish.

    • What will you actually measure (e.g., temperature, blood pressure, tumor size, ‘surrogate outcomes’ such as biochemical/radiological indices, survival time, relative risk).

    • What outcome is important for the veterinarian, for the owner, or for the patient? (e.g., survival is most important for owner or patient, reduction in the uremic breath odor might be important for owner).

  • PICO – Outcome: canine patients older than 10 years with chronic renal failure (attributable to glomerular nephritis) with on an ACE inhibitor in addition to standard therapy in comparison to the standard therapy of renal diet (low protein/phosphorus) lead to increased survival time and improved quality of life.

Background & Foreground Questions

  • Background question

    • Broader, more fundamental question about disease and conditions (often explained in textbooks).

  • Foreground question

    • Specific question about managing patients with a disease.

    • Components (PICO):

      • Patient or population

      • Intervention

      • Comparison to the intervention

      • Outcomes

    • In an older patient with X disorder, is giving Y treatment rather than Z treatment more likely to result in a shorter stay in hospital?

Steps for Practicing EBVM - SEARCH

  1. Formulate an answerable clinical question.

  2. Search for evidence to answer the question.

  3. Critically appraise the evidence.

  4. Apply the answer to your patient.

  5. Audit the outcome.

Types of Publication

  • Peer-reviewed

    1. Original research article

    2. Review

    3. Letter to editor (not really peer-reviewed)

    4. Editorial (not really peer-reviewed)

  • Non-peer-reviewed

    1. Conference and scientific meeting proceedings

    2. Textbooks

    3. The internet

    4. Government publications and reports

Search for the Evidence

  • Electronic databases for peer-reviewed scientific journals

    • PubMed

    • CAB abstracts

    • Web of Science

    • Web of Knowledge

    • Cochrane Collaboration

  • Conference proceedings: results are not fully reported.

  • Textbooks: out of date, look at the references.

  • Expert opinion: lowest level of evidence.

The Evidence Pyramid

  • Strong evidence (top of pyramid) to Weak evidence (bottom of pyramid):

    • Meta-analysis

    • Systematic review

    • Randomized controlled trial

    • Controlled trial without randomization

    • Observational study (cohort, case-control, or cross-sectional)

    • Case series / case report

    • Expert opinion

Keyword Search Examples

  • ‘Canine AND renal failure’ returns 3057 references.

  • ‘Canine AND glomerular nephritis’ returns 528 references.

Steps for Practicing EBVM - APPRAISE

  1. Formulate an answerable clinical question.

  2. Search for evidence to answer the question.

  3. Critically appraise the evidence.

  4. Apply the answer to your patient.

  5. Audit the outcome.

Critical Appraisal in EBVM

Steps:

  1. Are the study results valid?

    • Describe the evidence:

      • Study design

      • Epidemiological measures

      • Causality

      • Bias and confounding

  2. Are the study results clinically important?

  3. Are the study results relevant to my patient?

Critical Appraisal Checklists

  • Formal checklists for critical appraisal of different study types are available (e.g., https://casp-uk.net/casp-tools-checklists/).

  • Major guidelines:

    • CONSORT for randomized controlled trials

    • STROBE for observational studies – cohort, case-control, and cross-sectional studies

    • STARD for studies reporting diagnostic tests

    • Others (MOOSE, PRISMA) for meta-analysis and systematic reviews

    • REFLECT for veterinary randomized controlled trials (Conner et al. 2010, https://doi.org/10.1016/j.prevetmed.2009.10.008)

Cochrane

  • British international charitable organization of 37,000 volunteer experts formed to synthesize medical research findings using evidence-based approaches.

  • Conducts systematic reviews or meta-analysis of randomized controlled trials (mainly human medicine).

  • https://www.cochranelibrary.com/

Critical Appraisal in EBVM - Steps

  1. Are the study results valid?

    • Describe the evidence:

      • Study design

      • Epidemiological measures

      • Causality

      • Bias and confounding

  2. Are the study results clinically important?

  3. Are the study results relevant to my patient?

Clinical Importance - Example

  • How ‘big’ is the clinical effect?

  • Epidemiological measures

    • Odds Ratio, Relative Risk, Risk Difference

    • Difference between means or proportions

    • Confidence intervals

    • NNT (Number Needed to Treat): how many cases have to be treated to prevent or cure ONE additional case of the disease.

Clinical Importance – An Example

  • Mast cell tumors are common skin tumors in dogs.

  • Treated by surgery, radiation therapy, chemotherapy, or medications to fight secondary effects of tumors.

Clinical Importance – An Example - Palladia

  • 37% of Palladia treated dogs responded.

  • 8% of placebo treated dogs responded.

  • Risk Difference (RD) = 29%

  • Number Needed to Treat = 1RD=10.29=3.45\frac{1}{RD} = \frac{1}{0.29} = 3.45

    • You have to treat 4 dogs for one to have tumor remission due to the therapy.

Critical Appraisal in EBVM - Validity

  1. Are the study results valid?

    • describe the evidence

      • Study design

      • Epidemiological measures

      • Causality

      • Bias and confounding (internal validity)

  2. Are the study results clinically important?

  3. Are the study results relevant to my patient?

Relevance to Patient

  • ‘External validity’ or ‘generalizability’ of the study.

    • Are the study participants similar to my patients?

    • Can the results be applied to populations other than that which was studied?

    • You have to make the decision based on the description of the patients in the study.

Relevance to Patient - Examples

E.g., Therapeutic options of bovine virus diarrhea in small dairy farms in the Swiss Alps may not be relevant for American feedlots.

Steps for Practicing EBVM - APPLY

  1. Formulate an answerable clinical question.

  2. Search for evidence to answer the question.

  3. Critically appraise the evidence.

  4. Apply the answer to your patient.

  5. Audit the outcome.

Factors Influencing Treatment Choice

  • Efficacy of treatment based on evidence critically appraised.

    • What strategy gives the best patient outcome?

  • Cost: immediate cost and ongoing costs.

  • Convenience: E.g., Yearly heartworm prophylaxis versus daily.

  • Patient/owner preference, values, and expectations.

  • Clinical experience and skills.

Steps for Practicing EBVM - AUDIT

  1. Formulate an answerable clinical question.

  2. Search for evidence to answer the question.

  3. Critically appraise the evidence.

  4. Apply the answer to your patient.

  5. Audit the outcome.

Audit the Outcome

  • How well did the EBVM-derived treatment work for the patient of your individual client in your practice situation?

  • It’s important to ask the owner how the animal does after the treatment (by re-visit or over the phone).

    • If it did not work, clients choose another veterinarian but they usually don’t inform the first vet about the results!

    • You have to tell people to keep in touch and don’t persist with a treatment which is not working for them.

Audit the Outcome - PRACTICE

  • Important to keep good records so you can objectively measure the outcome of your management/treatment policies.

  • It’s beneficial to actually analyze practice records, which is easier these days with practice management software.

  • Leads to continuous improvement in practice.

Steps for Practicing EBVM - SUMMARY

  1. Formulate an answerable clinical question.

  2. Search for evidence to answer the question.

  3. Critically appraise the evidence.

  4. Apply the answer to your patient.

  5. Audit the outcome.

EBVM and the Client-Veterinarian Relationship

  • Clients are critical and have access to the same search tools (e.g., internet) -> You have to provide evidence-based advice.

  • Some clients wish detailed information if the animal will be cured, on any side effects, or on survival time -> You have to provide these details.

  • Others clients focus only on the outcome and trust your decisions -> You have to be confident in accepting this trust.

EBVM Challenges for Publication of Results

  • Peer-reviewed journals are usually not keen to publish the nonexistence of a treatment effect.

  • Peer-reviewed journals often do not allow publication of confirmatory studies.

  • Scientific data is sometimes retained for marketing reasons under the cover of confidentiality.

EBVM Challenges for the Busy Practitioner

  • Veterinarians have only limited time to consult databases.

  • Literature search is tedious and not all databases are freely available.

  • The amount of literature might be overwhelming or extremely limited in other cases.

  • The language of research, statistics, and scientific methodology is not necessarily understandable by practitioners.

  • Searching, accessing, and reading literature are not just fundamental concepts of EBVM, but are fundamental components of being a good veterinary scientist.

Further Reading

  • Stanley Robertson. Refining the clinical question: the first step in evidence-based veterinary medicine. Veterinary Clinics of North America: Small Animal Practice, 2007. 37:419-431.

  • MA Holmes. How to start practicing evidence-based veterinary medicine: a practical guide for over-worked practitioners. roceedings. 54th Annual meeting of the American Association of Equine Practitioners 2008. 327-335.

  • JM Vandeweerd, P Gustin, S Buczinski. Evidence-based practice? An evolution is necessary for bovine practitioners, teachers, and researchers. Veterinary Clinics of North America: Food Animal Practice, 2012. 28(1):133-9.