Field trials and clinical trialsPresentation Transcript
Field trials/ Clinical trials
Dr. Bhoj R singh, Principal Scientist (VM)
I/C Epidemiology; Centre for Animal Disease Research and Diagnosis
Indian Veterinary Research Institute, Izatnagar-243122, Bareilly, UP, India.
Types on the basis of purpose
• Pharmacological and toxicity trials: Either in Lab
animals or Target spp.
• Initial trials for therapeutic effect and safety: In target
spp. under controlled environment specifically to select
the most effective agent out of the several potential
ones, standardized the therapeutic/ prophylactic dose/
• Clinical evaluation of efficacy: On large scale, in field,
under operational conditions usually multi-centric to
evaluate the effect of several factors including
• Post authorization surveillance: To monitor adverse
Field trial Clinical trial
In healthy population On patients
Often prophylactic Often therapeutic (including
prevention of sequelae)
Relies on natural
For secondary and tertiary
Types of trials on the basis of control
• Uncontrolled/ Open: The same group /
individual is compared before and after
• Controlled trials: Treatment and Control groups
are always there.
– Concurrent Control
– Historical control
– Positive control
– Negative control
– Randomized control (Approach is similar as used for
On the basis of scale
• Exploratory trials: For proof of efficacy, less stringent.
• Confirmatory trials: Randomized controlled trials to
determine appropriate dose level, with stringent protocol.
• Composite trials: Combines both exploratory and
• Community trials: Experimental unit is entire
community, population of a defined area/ breed, sex,
• Multi-centric trials: May be for any purpose but mostly
for confirmatory objective with aim to recruit more
animals in the trial, to increase validity through having a
large cross section of population as study population.
• Superiority trials: To determine difference
between treated and control group, based on
• Equivalence or Bioequivalence trials: To
compare the treatments with almost same or
similar outcome for economy of the therapeutic
agent, availability, simplicity in use, acceptability
• Non-inferiority trails: To prove that new drug is
as good as the standard one.
Considerations before Trial protocol
Primary hypothesis: Feeding GN cake increases fat in milk. It is
identified by measuring the effect/ response variable e.g. milk fat
in milk of two groups, the fat % in milk is the Primary end point
(the end point which is clinically/ economically most important,
can be measured easily and economically) and Secondary end
points (type of fats/ fatty acids etc.). It should define the validity of
the hypothesis. In exploratory trials it is often desirable to use
more than one primary end point to cover the potential range of
effect as in this case concentration of milk protein, milk fat,
mineral contents, SNF, metabolic disorders, post-partem breeding
Determining the efficacy: For calculation mean values are taken
either as mean of all experimental units separately or in group, to
determine Treatment efficacy (λexp)
λexp= Fat % in GNC fed (T) – Fat % in control (C) / Fat% in Control (C)
• Experimental unit: Usually an individual animal, but in livestock allocation
of treatment groups (as in feeding trials when it is not easy to determine how
much feed an individual consumed, then animals in a household/ birds in a
pen may be taken as unit) . Sometimes there may be several units within an
animal as different quarters of udder may be separate units (for
intramammary infusion of treatment), two horns (horn cancer treatment),
different legs (for effectiveness of a lotion to be applied in foot rot, FMD
• Experimental population (EP): The population on which a trail is
conducted, it should be true representative of a Target population. If there
is difference in two populations then external validity of the findings will be
low. When there is biasness in allocation to groups (T and C) in EP then the
internal validity is low. Prophylactic trials often target the populations with
high risk of exposure or probability of development of a natural disease so
that natural challenge can have play.
• Admission/ eligibility and Exclusion criteria: For inclusion/ admission
protocol must precisely define the condition and criteria for diagnosis of the
condition. For exclusion, protocol must define the criteria of not including a
case in the study (as allergic to treatment, having some other condition/
disease, previous treatment etc).
• Blinding: Single, double, treble and open label (non blinded).
• General information (title, Name and add. of Investigator, sponsor, trial sites
• Justification and objectives (Need, reasons, primary hypothesis, primary end
point, secondary hypothesis to be tested).
• Design (Effect/ response variables, scoring system, affectivity definition etc.)
• Duration (Date of beginning, ending, duration of the target disease, period of
recruitment, duration of treatment, observation, rules for termination of trial).
• Experimental population (Unit, composition, inclusion/ exclusion criteria,
definition of cases, diagnostic criteria, selection of control, sample size, informed
• Therapeutic/ prophylactic procedure (Product formulation and identification,
dosages, placebo/ standard treatment formulation and identification, route and
frequency of administration, operators’ safety, environmental safety, blinding
method, compliance monitoring, definition of stage to stop intervention).
• Type of trial (randomization, stratification, implementation of allocation
• Data collection (dates, frequency, method of recording adverse reactions,
identification of experimental units, training/ standardization of data collection
and recording, confidentiality, communication with and between participants).
• Data analysis (Technique of unblinding, statistical method, significance level
and confidence interval for interpretation, method to ‘lost to follow up etc.)
• Parallel-group (Standard): Mostly in confirmatory trials, experimental
units (EU) are randomized for single treatment.
• Crossover design: EUs are exposed to more than one treatment
consecutively for each treatment EUs are allocated through
randomization. Applicable where treatment effect do not carry-over
in to subsequent treatment period.
• Sequential design: Conduction is dependent on the results obtained
so far and EUs enter the trial in pairs (T and C) and observed for
desired level of effect to enter in to second stage or terminate the
trial or to to increase the sample size (open trial). Significance tests
are conducted repeatedly on accumulating data, it tends to increase
significance over the time.
• Factorial design: If two treatments, A and B needs to be investigated
at two levels (a and b) then the factorial designs are made and in
this case we designate it as a×b factorial design. It is powerful but a
bit complicated design in 2x2 factorial design there are 4
treatnments viz., A, B, A&B, Neither A nor B.