Dr. Priyamadhaba BeheraJunior Resident

ARTICLE PRESENTATION ON CLINICAL TRIAL

12/04/2013

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Evaluation of Atorvastatin for the Treatment of Patients With Asthma: A Double-Blind Randomized Clinical Trial Abdollatif Moini, Ghasem Azimi, Abdolhay Farivar

 Impact Factor 1.913 

Outline of presentation

1.Summary of article (1-18)– introduction– objectives– Methodology– Results– Discussion

2.Epidemiology and biostatics concepts related to article (19-22) 3.Critical appraisal (23-30)

Introduction

• Asthma is a global health problem. Despite the availability of effective treatment, some patients develop a type of asthma that is insensitive to corticosteroid

• The anti-inflammatory and immunomodulatory effects of satins are well-documented

Objective

• the potential therapeutic effects of atorvastatin were investigated in asthmatic patients

 METHODLOGY

Study Setting Hospital -based

Study site asthma clinics of Arak University of Medical Sciences , Rahahan, Arak, Iran

Type of Study Randomised clinical trial

Sample Size 62

Study Subjects 18-70 years(grade2/grade3) asthmatic patients

Scales used Asthma Control Test Questionnaire(For primary out-come) 6

Geographical location of study site

• Inclusion criteria –mild persistent/moderate persistent asthmatic (grade 2/grade 3) aged in between 18 to 70 years

• Exclusion criteria1. taking satins at the time of study

2. h/o of sensitive to satins

3. severe asthma leading to hospitalization within a month prior to study

4. Smoking

5. hepatitis or active liver disease, myopathy or myositis,

6. pregnancy

Methodology

mild persistent to moderate persistent asthma (grades 2 and 3 of severity criteria for asthma) aged 18 to 70 years who presented at asthma clinics of Arak University of Medical Sciences from 24 October 2010 to 10 April 2011

73 agreed to participate

Volunteer patients were alternately allocated to the intervention and control group based on timing of entering study

Control group=6,intervention group=5

ASTHMA CONTROL TEST

• The ACT is a 5-item patient-administered survey for assessing asthma control

• Each of the 5 questions is given a score from 1 to 5. • Responses from the ACT are summed to yield a score

that ranges from 5 (poor control) to 25 (complete control).

• A cut-off score of 19 or less identifies patients with poorly controlled asthma.

Ethical clearance

• The research protocol was approved by the Scientific Ethics Committee of Arak University of Medical Sciences, and written informed consent was obtained from the volunteers

STATISTICAL ANALYSIS

• Statistical analysis carried out with software SPSS 16.0

• Chi-squared test and student t-test were used to compare the treatment and control group

• independent and dependent t-test were used for the comparison of groups and subgroups

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RESULT-1

RESULT-1 cont.

• Table 1.Demographic information continued

Result-2

DISCUSSION One probable reason for the lack of a significant clinical

response to satins in this study, as well as in other human studies, is that the therapeutic effects observed in vitro and in mice do not necessarily occur in humans

Favourable clinical response requires a higher drug dosage or a longer period of treatment, or that the variables selected in this study were insufficiently sensitive to show improved asthma control

atorvastatin is not effective for the treatment of mild to moderate asthma

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Limitations

• Did not have access to more sensitive quantitative methods for evaluating airway hyper-responsiveness and inflammation.

eg: using a peak flow meter, methacholine challenge test, CRP assay, number of saliva eosinophils, the fraction of exhaled nitric oxide, or alveolar nitric oxide.

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Randomization Randomization gives each participant a known (usually equal)

chance of being assigned to any of the groups. Successful randomization requires that group assignment cannot be predicted in advance.

Basic Benefits of Randomization• Eliminates assignment basis• Tends to produce comparable groups• Produces valid statistical tests (valid false positive error

rates)

Why Randomize?

• If, at the end of a clinical trial, a difference in outcomes occurs between two treatment groups (say, intervention and control) possible explanations for this difference would include:

• the intervention exhibits a real effect;• the outcome difference is solely due to chance• there is a systematic difference (or bias) between the

groups due to factors other than the intervention.

Randomization aims to obviate the third possibility.

Forms of Randomization

• Simple Randomization• Permuted Block Randomization • Stratified Block Randomization • Dynamic (adaptive) random allocation

Alternative allocation vs. Randomisation

• Some investigators incorrectly believe that an alternating assignment of participants to the intervention and the control groups (eg-ABABAB…..) is a randomization

• No random components exits in this type of allocation except the first participant

• A single-blind or unblinded study, the investigators know the next assignment that lead to bias

• In double-blind study, if the the blind is broken at one participant then entire sequence of assignment is known

CRITICAL APPRAISAL

CONSORT (CONsolidated Standards of Reporting Trials)

CRITICAL APPRAISAL-1

• Title and abstract are clear with study design, balanced summary of what was found

• Background explains the scientific rationale for the study

• In objectives they mention that the study, the potential therapeutic effects of atorvastatin were investigated in asthmatic patients ,but they have only considered grade-2/3 asthmatic patients in the study

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CRITICAL APPRAISAL-2

• Inclusion and exclusion criteria for participants are clear • Settings and locations where the data were collected are

mentioned• The interventions for each group with sufficient details to

allow replication, including how and when they were actually administered

• Completely defined pre-specified primary and secondary outcome measures, including how and when they were assessed

How sample size was determined is explained

CRITICAL APPRAISAL-3

• Detail description of randomisation is not given• Alternately allocation doesn't survey the purpose of

randomisation• Statistical methods used to compare groups for

primary and secondary outcomes are mentioned• A table showing baseline demographic and clinical

characteristics for each group• Participant flow diagram is given but steps of

randomisation and voluntary data missing is not clear

CRITICAL APPRAISAL-4• Silent about possible bias• Internal validity is questionable d/o selection

bais• Generalisability of this result is not possible to

all asthmatic patient as it uses grade-2/3 asthma in sampling

• Silent about funding

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THANK YOU

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