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VETS6103 RESEARCH AND ENQUIRY 1A

FORMULAE

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LEARNING OUTCOMES

General
o Appreciate the importance of using best available evidence for
professional practice
o Formulate relevant questions and source, evaluate and synthesise
evidence to answer these questions across a range of veterinary
contexts
o Create a database for scientific references (such as an EndNote
library), include references in writing articles and reports, and create a
bibliography
o Summarise and synthesise information from a journal article, a
scientific presentation or a report and prepare an abstract
o Design simple field experiments including randomised control trials and
critically evaluate the design of published experiments
o Analyse data from simple field experiments using a statistical program,
interpret results and present the result in a journal article, a scientific
presentation or an industry report; and
o Interpret statistical results from simple experiments presented in a
journal article, a scientific presentation or an industry report
Influence of research on policy and practice
o Identify the research methods used to describe the epidemiology of B.
suis in humans and animals in NSW
o Describe the policy response to the emergence of B. suis in dogs in
NSW and the approach taken to devising such a policy
o Describe the clinical presentation, transmission and clinical
management of brucellosis (B. suis) in dogs
o Describe the public health risks associated with B. suis infection in feral
pigs and dogs and suggest measures to reduce these risks
Acquiring
o Identify keywords, synonyms and related terms
o Create a search strategy for a veterinary clinical question using
PICO/PECO
o Search a database to find articles relevant to a clinical question
o Locate and access the selected articles
o Manage your references using EndNote
Ethics in research
o Identify important ethical issues in research
o Source and understand various guidelines on the ethics of biomedical
research
o Apply your understanding of ethics in your planning and/or
participation of future research activities and in the critical evaluation
and analysis of published research
Randomised control trials
o Explain the process of designing a clinical trail
o Identify key biases influencing validity of clinical trials
o Explain the reasons for control selection, sample size calculation,
randomisation and blinding
o Critically evaluate the design of a published study
o Evaluate reports of randomised control trials
o Determine what information from such reports are relevant to a clinical
question on treatment
o Design a simple randomised control trial
o Randomly allocate animals to treatment and control groups
o Prepare protocols for follow up of enrolled animals
o Make decisions on the appropriate method for assessment of the
outcome
o Critically evaluate the design of a published randomised control trial
o Formulate a clinical question on treatment
o Contribute to the design and conduct of a randomised control trial to
provide best evidence to address a clinical question on treatment

BIOSTATISTICS
Phases to statistical analysis:
1. Descriptive statistics description of population using key population
variables
a. Measure of location (mean, median)
b. Measure of variability (standard deviation, IQR)
2. Statistical inference use of study data to make inferences about the general
population
a. Estimation generation of confidence intervals of unknown population
parameters
b. Hypothesis testing
Determining presence of extremes:

DAgostino: <Q1-1.5, >Q3+1.5

Appropriate procedure for statistical inference depends on:

Number of outcome variables desired


Unit of analysis analysis has to reconcile dependencies if present, i.e. if unit
of analysis =/= individual
Type of primary outcome variable
o Continuous
o Discrete
Ordinal
Categorical/nominal
Distribution of primary outcome variable
Number of comparison groups
Whether groups are independent or paired statistical analysis needs to
account for within-subject variability
Assumptions of statistical tests:

Independence of sampling units v. important


Normal distribution of outcome variable can be violated more or less
according to test

EVIDENCE-BASED PRACTICE
Brucellosis:

Caused by gram- coccabacilli Brucella spp.


Infect various animals incl. humans
Chronic infections with recurrent flares causing abortion/swollen testes
In Australia:
o B. ovis (in sheep) not zoonotic
o B. suis (in pigs) zoonotic
o B. abortus (cattle and buffalo) zoonotic, but has been eradicated
thanks to EBP
Overseas:
o B. canis (dogs) zoonotic
o B. melitensis (goats) zoonotic

B. suis in pigs:

Present mostly feral pigs


o Considered pests allowed to be hunted
o A lot of hunters therefore source of pig-human transmission
Notifiable disease
Clinical signs
o Infertility
o Abortions/stillbirths
o Vaginal discharge
o Orchitis
o Lameness < incoordination < hind limb paralysis
o Arthritis
Bacteria present in
o Urine
o Faeces
o Blood
o Vaginal discharges
o Aborted animal foetuses
o Placenta
Can also happen in dogs
o Shedding of virus
In semen
In aborted foetuses
o Symptoms
40% asymptomatic
o Can transmit to humans according to current research
o Current policy: recommended euthanasia in NSW
o In pig-hunting dogs
Boxers
Wolfhound
Bull Mastiff
Bull Arab
o In farm-hunting dogs
Cattle dogs
Border Collies
Kelpies
o Tx
Recommended by NSW: euthanasia
In medicine: mixture of antibiotics (doxy + rifampicin) usually
on used humans
Test
o Ab test
Rose-Bengal Test (RBT)
If positive, Complement Fixation Test (CFT) only sensitivity 54%
Many anti-complementary (AC) reactions common, cause test
results to be inconclusive
Practice on brucellosis in dogs:

Risk-free: euthanasia
Treatment using doxy + rifampicin
More PPE when any procedures relating to reproductive tract
Testing dogs that have paralysis/reproductive symptoms
Testing all dogs in contact with infected dog

Discospondylitis: sore back


Response to brucellosis:
1. Largely ignored when only present in feral pigs and hunters have right to kill
pigs as they want
2. Dogs presented with B. suis
3. Research to find prevalence of feral pigs and prevalence of B. suis in them
4. Literature and policy review to find info about dog-human transmission
found possible
5. Policy response euthanasia recommendation
6. Enlist epidemiological specialists
a. Compare the number of +/inconclusive/- tests
7. Conduct research on existing tx used
8. Applying human tx to dogs and observe recovery
9. Publish research on new tx policy should not prevent research challenging
the recommended tx!
10.Policy changed according to research
11.Practice is changed according to policy new tx adopted
12.Further questions to be addressed:
a. Geographic prevalence & distribution
b. Migration and interstate transport
c. Risk for household members to infected dogs
d. Risk in hunting practices
e. Exposure and transmission risks in cattle
EVIDENCE-BASED PRACTICE

Traditional approach to Criteria Evidence-based approach to


clinical decision-making clinical decision making
Senior professional, government Information sources Peer-reviewed, research-based
compendium/legislation, consulted (list) literature
veterinary education, client
Medium Importance placed on Medium
clinical expertise (circle)
Medium Importance placed on High
research (circle)
Medium Importance placed on client High
values and situation (circle)
Medium Time required (circle) High
Networking Skills required (list) Ability to critique research
Good memory papers
Ability to search literature
effectively
What are the similarities?

What are the differences?

On the basis of the above exercise, how would you define Evidence-Based practice?

Information sources:
1. Research
2. Journal articles
3. Review articles
4. Text books
5. Reference books
6. Clinical experience and teaching
7. Websites
Evidence-based practice: integration of best research evidence with clinical expertise and patient
values
1. ASK: convert need for information into answerable question using PICO
a. Patient/population/problem
b. Intervention/exposure
i. Intervention: something the researcher applies to the individual/population
ii. Exposure: application due to external factors
c. Comparison to alternative tx
d. Outcome
2. ACQUIRE: find best evidence to answer
3. APPRAISE: for
a. Validity
i. Bias
ii. Peer-review look out for
1. Scientific layout (abstract, scientific process, references)
2. Academic credentials
iii. Chance variation explains results
b. Importance (size of effect)
c. Applicability
4. APPLY: apply by integrating evidence with clients preferences, particular circumstances
5. AUDIT: evaluate how well is working

How to practice:

Seek and apply EBP summaries produced by others


Practice EBP ourselves
Apply EBP suggested by someone else

->EBP about mindfulness: does the level of mindfulness meditation practiced correlate to the ability
to focus on complex mental tasks?
Types of questions:

Background question general information about what the issue/disease is can be found in
o Textbooks
o Reference books
o Review articles
o Reputable websites
Foreground question specific question that can only be answered by very specific research
o Can be found in
Research articles
Systemic reviews
o Can concern
Therapy
Diagnosis
Aetiology/harm
Prognosis

Learning Activity 2:

Write down one SCIENTIFIC question you have from the session on mindfulness meditation:

Is this a background or a foreground question?

Evidence-based medicine/practice (EBP): conscientious, explicitlfy and judicious


integration of both individual clinical expertise and best currently available
clinical research . The 5As:
1. ASK - Develop questions that need to be answered according to PICO formula:
a. Patient population and clinical problem patient demographic
b. Intervention what medical intervention is happening to tackle clinical
problem
c. Comparator what factors are being compared
d. Outcome what
outcomes
2. ACQUIRE - Decide on best
information source and
evidence type to answer
these and obtain it
a. Formulate an
effective search
strategy (test many
synonyms,
b. Use PubMed/Web of
Science/ Google
Scholar/ SCOPUS/
CAB abstracts
c. X AND Y AND (Z OR
W), zed*
d. Start broad, refine
gradually
3. APPRAISE appraise
evidence for:
a. Validity
i. Bias
ii. Statistical
significance
iii. Valid study design and data processing
iv. Quality of source
1. Peer-reviewed is best
2. Databases often only show peer-reviewed
3. Newspapers/reports often not peer-reviewed but latest
info
b. Importance of effect
c. Applicability
4. APPLY integrate with
a. Client preferences
b. Clinical circumstance
5. AUDIT evaluation
Databases:

Medline domestic animals with strong clinical focus need precision search
terms
PubMed mostly for genetics and molecular biology
Ovid
o Add key terms one by one if term is in their list of key terms, will open
window with related terms
Check explode to search all terms under the main term
Check focus to search mainly for one term
CAB abstracts
Zoological Record - exotic/zoo animals
o Use scientific names
o Refine search by selecting descriptors that correspond to question

Types of studies:
Meta-analysis statistical synthesis of many independent studies on the
same topic to obtain an overall conclusion
Systematic review qualitative comparison and synthesis of an overall
position based on many systematically-collected randomised controlled trials
(RCTs)/observational studies
Independent study
Cross-sectional analytic study presence/absence of disease/health-related
variables determined in each member of a study population/representative
sample at one particular point in time
Randomised controlled trial for questions about tx and diagnosis
Cohort study observational study in which a defined population followed
over a period of time and different subsets (according to exposure to a factor)
compared. Concern prognosis and aetiology/harm
o Prospective
o Retrospective
Case-control study compare people with disease/outcome of interest to
people from the same population without the disease/outcome of interest to
find link to exposure to particular risk factors. Retrospective
Research according to topic: different topics are best suited to different research
methods:

Topic Best Best study Best Search


evidence type database keywords
Therapy Systematic Randomised Medline Populatio
review controlled trial n AND
interventi
on
Diagnosis Systematic Cross-sectional Medline Populatio
review analytic study n AND
diagnostic
interventi
on
Aetiology Systematic Cohort/case- Medline Populatio
review control study n
Prognosis Systematic Cohort study Medline Exposure
review (intervent
ion) AND
outcome

Searching databases
Research terms:

AND between key terms that both need to be present in your source
(.OR.) between key terms of which only one needs to be present ->
broadening search
() nesting
* - truncation searches all terms with different suffixes to the term
Term.mp searches for terms only present in title, abstract, or as a subject
Term.tw (text word) searches for terms present anywhere in the article
POPULATION
ANIMAL CONDITION INTERVENTION

Hendra virus
History of outbreak:

1994
o Pregnant mare brought in and died
o 2 weeks later, further 12 horses died or euthanised
o Horses drown in their own lung fluids
o Virus forms syncitia on epithelial lining to form holes in lungs causing
plasma to leak out
o Blood collected for pathology, monitor signs and clinical disease
progression, post morterms
o On-site post-morterms
o Possible causes:
Poison deliberate or accidental monensin
1080
Paraquat
Arsenic
Bacteria
Anthrax
Legionnaires disease
Plague
Toxins
Botulism
Mouldy corn aflatoxin
Exotic disease
African Horse Sickness
Hanta virus
o Negative influence on industry
AAHL identified new virus by cell culture, direct horse inoculation
o Developed new assays to identify virus
o Equine morbillivirus
o Humans and horses tested for serological
Horse owners
Overseas virologist send a team to Aust
7 horses recovered but eventually died
1995-2000 :
o Environment of outbreak site monitored flying foxes
o One vet dies
o Flyuing foxes identified as seropositive 265 human cases, 105 deaths,
o Nipah virus outbreak Malaysia and Singapore
Tranmistted bats -> pigs -> humans
All pigs destroyed
Easily grown in cell culture
RNA virus mutate quickly
Transmission by responsiratory aerosols
Animal -> human -> transmission
Greater pathogenicity than hendra
Food-borne
2001 US
2008 2 mo
2009 held workshop to recommend vaccination to be prioritised for hendra
control
2010 Funding available from AAHL collaboration with CSIRO, unis,
2011 18 oubreaks
APVMA approved vaccine 2012
Hendra vaccie fully registerd 2015
AIN receiv
M102.4 monoclonal antibodies

Summary:

58 different ou

Distribution in bat species Australia:

Spectacled
Little red
Black
Grey-headed

Hendra virus development:


1. 2004 vaccinia virus
2. Ephrin B2 and B3 identified as cellular receptors for henipaviruses
3. sG glycoprotein recognised as immunogen
Properties of Hendra and nipah virus:

Requires both active and passive immunisation


Vaccine used sG

Bat-orginiating viruses:

ABLV
o ABLVp, ABLVs
o Menangle virus
o Cedar virus
o Other b

Research left to do on Hendra:

Diagnosis

ETHICS
Principles for Medical Research involving Human Subjects: World Medical
Association declaration of Helsinki

Medical research has to include human studies, however, they dont have to
include non-human animal studies if technique not intended for use on non-
human animals -> harder to justify
Health, wellbeing and rights most important
Generation of new knowledge should never be more important than test
subjects rights, life, dignity and interests
Stop when risks outweigh benefits
Research must have foreseeable benefits to them and to other individuals
Post-trial provisions
Only the welfare of animals is important compared to the rights, life, dignity
and interests of human subjects
Compensation/treatments offered to test subjects harmed rather than
euthanasia
Need to give informed consent only if able -> animals arent technically able,
but in humans, they must not be included in a research study that has no
likelihood of benefit for them or their wider group, and the research entails
only minimal risk and minimal burden
Focuses on vulnerable groups, to avoiding abusing your power as a
researcher can apply to animals as can be considered a vulnerable group

Influence on animal research:

Deontologically, lab animals lives, dignity and freedom of choice are as


important as humans
Therefore, principles that apply to human subjects apply to animal subjects as
well
Research must have benefits to individual animal or their broader
group/population, therefore shouldnt be done to benefit humans only
Made sure to protect vulnerable people from abuse of power
o People with difficulty giving consent
Children, esp. in care systems
People with mental health problems

o People with conflicts of interest forcing giving consent
o Homeless people
o Prisoners
o Coma patients
o People from low socio-economic backgrounds
o People of low education levels
o Relatives to researchers
Animals can be considered as humans mentally and physically incapable of
giving informed consent, therefore
o Research can be done if allowed by owner/representative or can be
done regardless if no owner, BUT only if:
Research involves only little risk
Research has benefit to them AND wider group -> no testing for
human medicine
o If animals bred specifically for research, however, breeder would be
representative -> can consent to harsher research treatment on their
behalf
o Are they a representative if they do not represent that animals rights
and interests, but the interests of the study? -> no
For research beneficial to that particular species:
o The risk to the animal should not outweigh the benefits to the species
o Rights, life, dignity and interests of individual should be more important
than the research goal
o Treatment should be offered to animals that suffer negative effects
because of research

Comparison with actual legislation: Australian code for the care and use of
animals for scientific purposes, Section 1: Guiding Principles

No distinction made between use of animals for furthering animal medicine


and for furthering human medicine
Only the wellbeing needs to be considered rather than the rights, interests,
and it merely needs to be supported rather than prioritised over research
goals
Pain only needs to be avoided or minimised rather than being completely
prohibited
Mentions that benefits must justify breaches of welfare rather than welfare
of the animal balancing out research benefits
Assumption that pain and distress in animals is similar to that in humans
except if exceptionally disproven
Death as an endpoint, and euthanasia as a treatment, are considered -> life
of the animal is not important
Researcher is able to breed animals

Type of research in veterinary science:

Testing a new surgery/treatment technique


Improving husbandry systems
Understand disease processes and risk factors
How
Animal behaviour and interaction
Animal physiology

Types of research:

According to
o Pure/basic
o Applied
Accordig to
o Positivist
o Anti-positivst
Methods of research:

Laboratory experimentation
Observations
Questionnaire
Quantitative/qualitative analysis

Influence on research:

Group benefitting from research


Species
Owner

Hx human experiment:
1. Began in anveint Greece
2. Systemised scientific research
3. Backlash over first research carried out without consent
4. Self-experimentation focused on
5. Nueremberg code 1947
6. Declaration of Hlsinki
7. Scandals continued to happen
Hx animal experimentation:
1. Started in Greece
a. Anatomical studies on dead animals
b. Vivisection and physiology on live animals
2. Ans
Animal-human interaction: specific to research
Ensuring welfare in animal research:

3Rs
o Refining
o Reducing
o Replacement
ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments)
Client-owned animals
o Obtain informed consent
o Owner = representative

Level of consent required:

Patient records need written consent

Impact factor: number of citations as a ratio of number of papers published


annually

Level of human medicine trials:


1. Level 1 laboratory trial
2. Level 2 proving that product is safe on humans in a controlled study
3. Level 3 proving efficacy in an actual human population
Types of experiments:

Clinical trials
o Randomised controlled trials (RCTs) two diseased groups selected and
outcome of tx compared to control
Cross-over trial animals serve as their own control and
switched to alternate intervention after a period of time, incl.
wash-out period, esp. when tx alleviate rather than cure
condition
Minimises need for large sample size
Minimises between-animal variability
Good for chronic disease with slow progression
Bias can occur if carry-over effects beyond wash-out
period
o Challenge trials disease outcome deliberately induced by
investigator, then randomly assigned to intervention group useful for
infectious disease
Can use smaller sample size, since sample population included
can be more similar (as disease is induced)
Attenuated/modified strain of disease agent often used low
external validity
Lower quality of evidence compared to RCTs

RANDOMISED CONTROLLED TRIALS


Randomised controlled trial (RCT): experimental design used to evaluate efficacy
of tx under real world conditions

Deliberate disease induction and subsequent tx


Important components
o Selection method for population
o Approach to allocation of intervention and
control group subjects
o Concealment of allocation
o Outcome definition
o Management of withdrawals from study
Types of randomisation used:
o Block randomisation if tx groups small to
ensure important parameters (age, sex,
etc.) evenly distributed
o Stratified randomisation assigning to different levels of a group,
corresponding to different levels of a factor
o Simultaneous non-random controls
o Historical controls
Control/comparison group used can be
o Positive controls (e.g. currently best available treatment) where
providing no tx is unethical
o Negative control
No tx
Sham tx (includes procedural control)
No disease exposure
Descriptive statistics of tx groups should be provided to make up for any
remaining selection bias
o No formal statistics should be carried out on descriptive statistics, as
diff. due to random error by definition
o If seem too different, use:
Stratified analysis
Adjusted statistical analysis
Rerandomisation (if covariate data available)
Outcomes should be objective where possible
o Can be either
Surrogate measure not direct measure of outcome of disease
Direct measure
o Needs to be determined before the start of the study to determine
required sample size
Can obtain incomplete results due to:
o Study subject lost (by choice or necessity for ethical reasons/death)
o Non/incomplete compliance with intervention regime

Analysis of incomplete data: can be either

Intention-to-treat (ITT) - comparison of all study units as they were originally


intended to be treated, whether they were or not considered best option
since maintains randomisation and mimics real-life occurrence of non-
compliance
Compliers-only analysis - comparison only of sample units who complied
completely with intervention
Analysis of study units according to intervention actually received

CONSORT: Consolidated Standards of Reporting Trials min. recommendations


for adequately reporting RCTs and randomisation/blinding procedures in general
Veterinary vs human RCTs:

Study participants dont enter study of their own accord


Challenge trials are often used
Common housing and tx of participants
Non-clinical outcomes (e.g. production outcomes)

REFLECT: Reporting Guidelines for Randomised Controlled Trials in Livestock and


Food Safety
Blinding: preventing individuals from knowing which sampling units are assigned
to which trial

To who is being recruited to the study


To intervention sampling unit is receiving
To group sampling unit is allocated to

Equipoise: the state of no preference existing between interventions in a study

Individual equipoise equipoise exists on basis of single


practitioner/researcher
Clinical equipoise entire profession

Results of a RCT should be:

Valid for animals in the study (i.e. high internal validity)


Conclusions made should be:
o Biologically plausible
o Able to be generalised to a broader population (i.e. high external
validity)
This requires minimal bias
Populations defined for study:

External/general population pop to which results may be extrapolated, dep.


on results
Target/eligible population pop to which results can definitely be extrapolated
Study population population of sampling units selected to participate in the
study
Unit of interest
Sampling frame list/organisation of sampling units in target population, used
for random selection
Source population population from which sample units are sourced should
be same as target population for external validity
Qualifying results:

Accuracy low random and systematic error = precise + valid


Precision low random error
Validity low systematic error
o Internal degree to which results are valid for the target population,
i.e. low study flaws and systematic variation
o External degree to which results can be generalised to the external
population, e.g. representative sample and study design
Bias: systematic error in design, conduct or analysis of a study that renders the
results invalid which is independent of sample size

Selection systematic error in selecting study groups within target population


causing diff baseline characteristics. Affects internal validity by causing
incorrect estimate of f or effect. Different from biased sampling strategy
o Inappropriate selection of study pop
Non-random selection
Failure to define target pop
o Non-random assignment of subjects to tx
o Omission of study subject due to missing data/loss of animal from trial
o Selection case and control subjects with different ranges of exposure
experience
o Self-omission of study subjects from study
Information bias in obtaining information about units of sampling
o Non-measurement bias bias in obtaining nominal/binary data (i.e.
exposure, risk factor, disease outcome, confounders)
o Measurement bias bias in measurement of continuous variables
o Misclassification bias subjects are misclassified according to tx type
Non-differential misclassification misclassification rate is equal
in all treatment groups
Assumed endemic problem with all study designs
Assumed to tend results to H0, except when low level of
exposure/low prevalence of outcome factor
Can cause under-adjustment of confounder if present in
confounder classification
o Caused by:
Observer error
Systematic instrument error
Subject error
Performance bias systematic diff in care provided/exposure to risk factors
between groups helped by allocation blinding
Reporting bias tendency to not report non-significant findings
Detection bias systematic diff in how outcomes determined between groups
helped by using objective outcomes and blinding
Attrition bias systematic diff in withdrawals from study/inconclusive results
between groups
Confounding association of study factor with other factor which influences
disease outcome
o Must be:
Indep. Risk factor for outcome of interest
Be associated with study factor in source population such that
confounder unevenly distributed between study groups
Not be result/in causal pathway of study factor/disease outcome
o Adjust for by:
Calculating measure of effect and including in statistical analysis
Matching study groups on confounder
Other biases specific to type of experiment/analysis

Bias summary:

Type of bias Description Mediation techniques


Selection Systematic diff between Sequence generation
characteristics of groups compared Allocation concealment
Performance Systematic diff in care Blinding of participants and
bias provided/exposure to risk factors personnel
between groups
Detection bias Systematic diff between groups in Blinding of outcome
how outcomes determined assessment
Attrition bias Systematic diff between groups in Incomplete outcome data
withdrawals from study
Reporting bias Systematic diff between reported Selective outcome reporting
and unreported findings

Biased sampling strategy: sampling from a smaller subset of target population


than intended or in a way that makes sample non-representative of target
population. Causes low external validity
Effect of analgesic therapy on clinic outcome measures OA:

Aim of study:
o Determine if multiple outcome measure of OA Rx is better than single
outcome measure
o Determine if a placebo is necessary for client-owned dog clinical trial
o Compare 3 different popular analgesics to each other
Recruitment:
o Not triple-blinded need the recruitment to be blinded too
o Not properly reported does not indicate who performed the
examination, or how allocation was blinded for person performing PE
(assumed not)
o Carprofen group had a lower severity level -> could affect level of
success
o Included dogs previously treated for OA or joint injuries -> affects
success of clinical trial
o Included dogs currently receiving tx for OA -> skew results
o Included dogs with all levels of OA, which means degree of success of
tx depends on initial condition
Randomisation of tx allocation avoids selection bias
o Groups not re-randomised in response to significantly different age
distributions -> source of selection bias
Blinding
o Double-blinded (assumed blinding for (1) individual allocation to group,
and (2) group allocation to tx)
o Blinding was not reported for either (1) or (2)
Effect of tx was found to be correlated to clinical severity at start of trial, even
though this seemed to be different between groups -> not corrected for
General population: dogs with osteoarthritis
Target population: client-owned dogs with osteoarthritis
Sample population: client-owned dogs with radiographically and clinically
evident osteoarthritis in at least one hip
Potential biases:
o Biased sampling strategy sampling strategy by referral and ads could
select for dogs with severe OA, otherwise o and vets would not make
the effort to join the study -> good bias, since the more severe, the
harder to treat, so underestimates effectiveness of tx
No recruitment blinding
o Selection bias randomisation was carried out but not allocation
blinding (or at least was not adequately reported), causing different
distribution of OA severity, which was not corrected for/re-randomised
-> could cause smaller effect in Carprofen group
No attrition bias observed
No other biases evident
Conclusion: results have suspected low internal validity due to lack or
incomplete reporting of blinding, affecting the external validity

TPLO: tibial plateau levelling osteotomy, surgery for cranial cruciate ligament
rupture

DESIGNING CLINICAL TRIALS

Traditional approach Evidence-based approach


Apply textbook instructions Conduct research
Apply what was learnt in Search and critically evaluate
veterinary studies literature
Talk to senior veterinarians
Take advice from drug
representatives

Types of studies:

Observational often to study risk factors and causes


o Cross-sectional
o Case-control
o Cohort
Experimental apply intervention
o Lab experiments
o Clinical trials

Ethical issues with controls:

Ethically cannot use non-treatment controls in some studies if animals


quality of life/survival chances negatively affected by
In studies where pain/poor quality of life is likely, have

Avoiding bias:

Avoiding selection bias


o Randomisation of tx allocation
Ensures balance between groups with respect to confounder
Avoiding confounding factors
o Blocking e.g. having control and tx group on different areas
Avoiding
Blinding
o Handler who gives tx (single blinding)
o Assessor who obtains
o Statistician who collates results and draws statistical conclusions
Use statistical analysis to analyse differences
Calculate sample size before start of trial

1. Calculate sample size before starting


2. Select control and comparative group
3. Random allocation to groups
4. Follow both groups similarly
5. Practice single, double, triple blinding
6. Use objective outcome
7. Appropriate statistical analysis
8. Report both significant and non-significant results

Equine gastric ulcer syndrome (EGUS) in adult horses

Up to 100% prevalence in racehorses, 40% training for 60% pleasure horses


Diagnosis
o Oesophagogastroscopy
Tx
o Protein pump inhibitors (e.g. omeprazole)
Complicated and multifactorial
Different forms
o Non-glandular (part of stomach) form in adults
o Glandular form in neonates and foals
o According to endoscopic appearance of ulcers
o Based on no. and severity of lesions
Signs
o Lack of appetite
o Weight loss/poor body condition
o Recurrent colic
o Loose faeces
o In foals
Less time spent suckling
Poor body condition
Diarrhoea
Bruxism
Ptyalism
Colic

Colic: abdominal pain

Effect of T-cell peptides derived from Fel d1 on allergic reactions and


cytokine production in patients sensitive to cats: a randomised
controlled trial
Issues with RCT design:

Classifying severity of asthma and allergies and ensuring equal distribution


between groups to ensure samples are balanced and there are no
confounding factors
Outcomes need to be measured at approximately the same time (within a few
d for this trial) in order to be comparable both qualitative and quantitative
Variation in outcome measurement different in order to eliminate the
confounding factor of pollen allergies
Should have collated more information about other allergies in each study
group
Justification for ITT analysis
Maintaining identical sample size 16 tx and only 8 placebos but due
results showing that 50% of tx will get late reaction which needs to be
assessed for influence on outcome in order to reduce confounding factor
Double-blinded
Use of several outcomes to ensure all the aspects of the aim of the study is
catered for, i.e.
Levels of blinding:
o Patients
o At administration of tx
o At analysis of tx
Use of a placebo
Method of randomisation
Variation in administration times by 1d
Representative recruitment to study
Included trial organisation
Apparent lack of attrition bias same number of patients lost to each group
Balance in group characteristics not well balanced, but none of factors
would reasonably have an effect
Calculation of sample size