Pervasive Developmental Disorder in Children - Research Paper Example

MODULE 6- INTERPRETATION OF STATISTICS AJ Wakefield, S H Murch, A Antony, J Linnell, DM Casson, M Malik, M Berelowitz, AP Dhillon, MA Thompson, P Harvey, A Valentine, SE Davies , JA Walker Smith. Illeal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet 1998; 351: 637-641 1. The researchers found intestinal pathology in 10 autistic children referred to a paediatric gastronomy unit. Is this evidence that intestinal pathology is more prevalent in children with autism than in children without autism Justify your answer. Suggest a comparison, i.e. a study design which could help to answer this question more fully 2. The ages of the children at the time they underwent intestinal investigation is given in Table 1. Assume that all the children had their MMR immunisation at age 1 year. On average how much time elapsed between the MMR and investigation (calculate this) 3. In Table 2 in the column headed 'Internal from exposure to first behavioural symptom' all the children are reported as having their first behavioural symptom shortly after MMR. 4. From the Results section of the paper (paragraph 2) how was the time of the onset of first behavioural symptom determined Discuss any potential bias associated with this method of measurement. 5. Which study design would avoid this sort of bias (Non availability of information due to failure of opening of the attached PDF file) KM Madsen, A Hviid, M Vestergaard, D Schendel, J Wohlfahrt, P Thorsen, J Olsen, M Melbye. A Population-Based Study of Measles, Mumps and Rubella Vaccination and Autism. N England J Med, 2002 347: 1477-1482 1. Research question and design a) What is the main question addressed in this study Answer: This observational study mainly addresses the following question: Whether there is any positive relation between autism and vaccination against measles, mumps, and rubella (MMR) Or in other words, is autism directly influenced by vaccination against MMR b) What are the advantages and disadvantages of using a cohort study rather than a case-control study or a clinical trial to answer the question Answer: Unlike case control study, cohort study gives the freedom to include samples both from affected (diseased) and unaffected (without disease i.e. control) pool. We can compare the effect of a specific phenomenon on both the population types simultaneously and draw inference accordingly through cohort study. Although, the cohort study is more expensive but, the validation of information on exposure is complete and always provide enough information on incidence rates of the diseases. Cohort study is a rare exposure and minimise bias in the exposure determination. But sometimes the diseases are rare. In that situation case-control study is a must which Examine multiple etiologic factors for a single disease. c) How was the cohort selected Answer: The cohort was selected on the basis of data obtained from the Danish Registration System and five other national registries. d) How were cases identified Were diagnoses confirmed using standard criteria Answer: Information from the Danish Civil Registration System was used to identify the link from the accompanying adult to child. Thus, 98.5 percent of children were identified with the use of child's civil registry number or the civil-registry number of father or mother and the age of the child at the time of vaccination on the basis of additional information The remaining 1.5 percent of children were identified on the basis of additional information from Danish Civil Registration System on other relatives and information on the address at the time of vaccination. So far as the diagnosis is considered, all diagnosis were based on standard criteria like International Classification of Diseases, 10th Revision (ICD-10) which is similar to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) with regard to autism. e) Is this method of case ascertainment likely to identify all cases of autism in the cohort If some children with autism in are not identified how would this affect results If some children are identified as cases when in fact they are autistic how would this affect the results Answer: Yes, the method of case ascertained likely to identify all cases of autism in the cohort. If some children are identified with autism are not identified the p-value will change and there will be shifting. Similar is the case when some children identified as cases of autistic without any autistic disease. f) Were the assessors of outcome blind to exposure Answer: Yes, they were blinded to certain factors associated with autism such as the inherited genetic conditions tuberous sclerosis, Angleman's syndrome and the fragile X syndrome. The paper mentions that data on the children with the inherited generic conditions which autism is associated with was kept censored from the assessors i.e. those who diagnosed, but does not specify whether they were aware of the MMR vaccinations status. 2. Taking account of important potential confounding factors a) What are the important confounding factors identified by the authors Describe how age might be a possible confounder Answer: For reporting the results, the incidence-rate ratios as relative risks was possible by confounding according to age(1,2,3,4,5,6,7,or 8 to 9 years), sex, calendar period (1992 to1993, 1994,1995,1996, 1997,1998,or 1999: for other autistic-spectrum disorder, the years 1992,1993 and1994 were grouped together,) socioeconomic status six groups, mother's education(five groups), gestational age (six groups)and birth weight Rs3,500 to3,900. b) From Table 1, which of the characteristics described is potentially a cofounder and why Answer: In the table 1, among all characteristics, age at diagnosis of autistic disorder is potentially a confounder because it is having p value of 0.87 which is highest. c) How were potential confounders dealt with in the analysis Answer: The potential confounders with the exception of age resulted in estimates of risk. Changing the start of the follow-up for autistic disorder and other autistic-spectrum disorders to the date of birth or 16 months of age had little effect on the estimates. 3. Magnitude and significance of the results a) What was the main risk factor under consideration Answer: The main risk factor under consideration was children between 24-29 months of age. b) In Table 2 the results for autism and vaccination are given as: Vaccination Person-years Number of cases Adjusted relative risk No 482,360 53 1.00 Yes 1,647,504 263 0.92 (0.68-1.24) Why is the relative risk for the unvaccinated children 1 Answer: In unvaccinated children the relative risk is determined by first establishing a baseline, an accounting of how autistic disorder is in the general population of children. An increase in risk would result in a number larger than 1.0. A decrease in risk would result in a lower number, and indicates a protective effect. 4. Interpret the information contained in the result shown for the vaccinated children. Include in your discussion: How precisely was the effect estimated What information is conveyed by the confidence intervals for the estimated effects (look at the lower and upper limit of the CI) Answer: The effect was estimated with 95% confidence interval or coefficient. I other words it allows only 5% human error during sampling, data collection, handling and processing. Were the results statistically significant, if not; was the power of the study stated Answer: The results were statistically significant for P value >0 .005. The power of the study reflected 95 percent confidence intervals 5. Evidence from both studies For each study write one sentence that summarizes what you consider to be the most important finding of the study. Answer: Firstly, the risk of autism was similar in vaccinated and unvaccinated children. Secondly, neither autistic disorder nor other autistic-spectrum disorders were associated with MMR vaccination. Briefly discuss the main strengths and weaknesses of each study. Answer: Strengths: 1. The study was based on individual reports of vaccination and diagnoses autism in well defined geographical area. 2. The Analyses were based on complete follow up data Weaknesses: 1. No information on the presence or absence of a family history of autism, which could explain our negative findings only if families with a history of autism avoided MMR vaccination. 2. In all analyses, when risk estimates were calculated, the possible confounders like age, sex. calendar period, socioeconomic status, mother's education, gestational age, and birth weight changed the estimates except age. 6. Based on the information in these studies, what advice would you give to a friend with a 1 year old child who has not yet had the MMR vaccine, and why Answer: Based on the information in these studies, I would suggest a friend with near about 1 year age child to undertake vaccinations the p value is 0.000058 which is < 0.005 level for significance in Chi-square analysis. Read More