Dr. Priyamadhaba Behera Junior Resident ARTICLE PRESENTATION ON CLINICAL TRIAL 12/04/2013 1
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
• 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
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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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-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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