Protocol Efficacy Parameters 2.4

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Efficacy Parameters

Major efficacy parameters for most disease are well established

butDefinite protocol should select those tests and parameters within the limits of resources available to the clinical trial e.g.

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Choosing efficacy parameters

1. Objective measurements that have been validated and widely accepted

e.g.- B.P. reading- Insulin serum- Glycosolated haemoglobin- Lipid ratios

2. Direct visualization and measure of lesion

e.g. Ulcer – endoscopyarterial blockage - angiotumor size – X Ray or PET

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3. Reduction in the progress or even reversal of the disease

e..g reduction in the severity of lesions

reduction in manifestation of the disease

reduction in duration of the disease

4. Improved symptomatology of the patient

5. Improvement of biochemical and lab parameters

6. Improved “Quality of Life”7. Clinical global evaluation by the

Doctor and patient8. Reduced mortality in those trials

where this parameter has relevance.

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Note :

The +ve and –ve points of each efficacy parameter incorporated in the protocol must be evaluated against the increase, it will cause to –

a. Time requirementsb. Personal effortsc. Financial costsd. Additional complexity especially to

the statistical evaluation of the final data.

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What are the best parameters?Which parameter to select in a

protocol ?A. Combination of parameters that are

practical and make sense to measure should be the best.

Parameters of different targetsa. Objective – Clinicalb. Subjective – symptomaticc. Biochemicald. Pathologicale. Pharmacologicalf. physiological

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What are the parameter that determine better efficacy over standard treatment?

DIRECT

a. Time of onset

b. Magnitude of effect

c. Duration of effect

d. Decreased rate of relapse

e. Improved quality of life

INDIRECT PATIENT COMPLIANCE

f. Decreased number of tab/day or dose / day

g. Better taste

h. Lower cost

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Factors affecting efficacy

a. Physical positionb. Relax or exercisec. After cold or warm bathd. Patient empty their bladdere. Prior to meal timef. Tests at various time of the day

(Circardian rhythm)

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Example disease where parameter to measure is clear Hypertension - B.P. reading

Here these are many subparameters -a. Fall in B.P. of 10 mm or moreb. Fall in B.P. to desired level – Normal c. Fall in B.P. over x no. of weekd. Maintenance of B.P. over y no. of

monthse. Maintenance of normal level BP for

z no. of monthsThe choice of one or more of the

above depends on objective of protocol and should be definitely decided before the study is initiated.

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Example of disease when parameter to meet is more

complicatede.g. post myocardial infarction –

treated to prevent re-infarction and sudden death

- Follow up for reinfarction – angiography

- No of deaths after 1 year – 2 year

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Efficacy Parameters in Preventive Therapy

A. Prevention of disease : e.g. VaccineB. Prevention of episodes of disease i.e.

number, duration or severity of episode is decreased e.g. asthma, epilepsy.

C. Prevention of progress of underlying disease.R1 to prevent more serious sequelae of this disease.e.g. lowering BP, lowering lipids, lowering blood sugar etc.

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Preventive TherapyA. Vaccine – Efficacy Parameter

a. Prospective Epidermiology Protocolb. Prospective & Retrospective protocolc. Protective level

B. Preventive of Episode of disease during last 1 week / 1 month how many episode has the patient experienced

012-56-10

C. Preventive of progress of disease Periodic evaluation of parameters-effect of disease on target organs

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Other Efficacy Parameters

A. “Escape medication” e.g. gastric ulcers, asthma, knowingly incorporated into the protocol. Use Antacid sos or ventoline sos evaluate the frequency of use of escape medication under treatment with the trial during as compared to the baseline or in case of crossover design the placebo period.

B. Decrease in dose of supportive therapyC. 5 years survival in case of cancer therapy

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Criteria to measure efficacy

1. All or none – Presence of absence criteria

2. Graded criteria applied to a. Subjective

as well asb. Objective symptoms and signs

3. Global criteriaa. Dr. evaluationb. Patients evaluation

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Grading Systems for efficacy parameters

A. 0 Not at all B. 0 Absent 1 Mild 1 Slightly present 2 Moderate 2 Clearly noticeable

3 Markedly 3 Definitely present

4 Severe 4 Continuous & gross

e.g. Pain e.g. skin rash

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0 Absent

1 Rarely present (occurs less than _____times per___)

2 Occasionally present (occurs less than __ times)3 Often present (occurs __ to __

times per ___)4 Almost always present (occurs

more than __ times per __)e.g. asthma attack

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Extended parameters e.g. asthma

No. of attacks per ____ frequencyHow severe was the attack severityHow long did last attack last duration

(each of these parameter can also be graded)

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Type of End points used to measure efficacy1. Time for a parameter to improve by a fixed

percent (50% or 75% or 100%)2. Magnitude of improvement at a fixed time

i.e. (after 1 week, 1 month)3. Duration of improvement while on

maintenance therapy4. Time to recurrence of symptoms after

treatment is stopped5. Degree of recurrence of symptoms after

treatment is stopped6. Any subjective parameter improvement7. Any “quality of life” parameter improvement

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Methods of Evaluating efficacy parameters

Compared to baseline or placebo

A. Active drug

B. Baseline or placebo or comparative drug

1. Ratio : AB

2. Incremental change : A minus B3. Proportionate change : A-B

B4. Percent change : A-B x 100

B

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Efficacy parameter with drawing

Eg. Gastric ulcer End Point

100% Drug A = Clinical Symptom

0% of patients Drug BWith healed = Endoscopy

Ulcers 0

Time100% Drug A

0% of patients With ulcer Drug B = Endoscopy Recurrence

0 Time

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VISUAL ANALOG SCALESProvide quantitative measures to subjective rating e.g. stress, anxiety, alertness, depression, hunger, itchPain parameter has been proved to be reliable measured by these scales. Date Time of assessment Score

0 10

No pain Very severe pain

0 % 25 % 50 % 75% 100%

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Patient DiariesDate from Patient Diaries give important efficacy information in outpatient evaluation e.g. antiepileptic treatment evaluation anti diarhoea treatment.

- The diaries should be designed to make it user friendly.- Instruction for filling the data should be discussed with the patient and printed on the

diary.- The diary should be kept with the patient all time i.e.

at the bed at night

- Pen or pencil to enter data on the diary should be sealed to the diary- Diary should be collected by investigator frequently i.e. weekly or biweekly.

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Quality of Life

There are a few formal definitions of this term

The term “Quality of Life” is used loosely by many

We shall only discuss health related Quality of Life

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Schipper et al (1990)

“Quality of life represents the functional effect of an illness and its consequent therapy upon a patient as perceived by the patient”

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Four areas contribute to the overall effect

1. Physical and occupational

function

2. Psychologic state

3. Social interaction

4. Somatic sensations

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Components of Quality of life Tests

I Physical and occupational

a. Capabilities

b. Dysfunction

c. Amount of time at works

d. Work status

II. Psychological

a. Neuropsychologic function (eg. Perceiving, thinking and remembering)

b. Emotional state (eg. Anxiety, anger, depression)

c. Personal productivity

d. Intimacy and sexual function

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III. Sociala. Number of contacts per week /

monthb. Quality of social contacts at home,

school, jobc. Quality and quantity of social

contact with friendsd. Interaction at worke. Recreational activitiesIV. Somatic sensationsa) Sleepb) Painc) Bowel movements etc.

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Is an End point an End point?e.g. Blood pressure measurement