Title: Cutaneous Adverse Drug Reactions in Indian population: A systematic review Review question(s) To carry out a systematic review of the published evidence of the cutaneous adverse drug reactions in Indian population Searches 1. Sources for search include: (i) Electronic databases: PubMed, MEDLINE, PUBMED Central, Google Scholar, Cochrane (iii) Bibliographies of relevant articles. (iii) Indian journals publishing the articles in the field of dermatology, pharmacology and adverse drug reactions available on internet 2. Time period to be considered by the review: From Jan-1995 to April -2013 3. Language restrictions: Articles in English language only will be included 4. The search strategy will include the following key search terms: cutaneous adverse drug reaction OR Dermatological reaction OR Drug induced skin reaction AND ( India OR Indian population ). Search Strategy for Mediline 1. Cutaneous adverse drug reaction 2. Dermatological reaction 3. Drug induced cutaneous/skin reaction 4. Drug related cutaneous/skin problem 5. or/1-4 AND India 6. or/1-4 AND Indian Population Types of study to be included 1. Observational studies (case series and cohort studies) Condition or domain being studied Cutaneous reactions are common type of adverse drug reactions (ADRs). They hold special importance in healthcare because of patients suffering, requiring hospitalization and occasionally fatal incurring economic burden. Among the various cutaneous adverse reactions itching, skin rashes, urticaria, fixed drug eruptions, angioedema, and contact dermatitis are common. Stevens-Johnson syndrome, and toxic epidermal necrolysis are rare but serious form of ADRs affecting patient's life. Antimicrobials, analgesics and antiepileptics are common groups of drugs involved. However, the pattern and the drugs causing cutaneous reactions can vary due to different prescribing habits, use of newer drugs and referral bias. Observational studies are important tools to know the pattern of reactions and causative drugs for ADRs. The studies conducted in this field from India are of limited durations and smaller sample size. Hence, a systematic review is required to generate the large scale epidemiological data for cutaneous ADRs in India.
Participants/ population Inclusion: - Studies on Indian population only - All cohort studies related to cutaneous reactions - All case series which have described at least 10 cases of any cutaneous reactions - Studies related to adverse drug reactions or cutaneous adverse drug reactions which have described at least 10 cases of any cutaneous reactions - All age groups and clinical settings (Indoor or outdoor patients) - Causality analysis or sufficient information about de-challenge and re-challenge for the selection of causative drugs Exclusion: - Studies which is not based on Indian population - Retrospective studies - Selective studies on specific reactions (e.g., Stevens Johnson syndrome, toxic epidermal necrolysis, etc.) only - Studies which focus on intensive care or fatal or life threatening cases only - Selective studies referring to a particular drug exposure (e.g., anti-epileptics, NSAIDs, etc.) only - No or insufficient information about causality analysis - Studies which have not specifically described the causative drugs - Case series or case reports with less than 10 cases of cutaneous reactions - Editorials, Letter to editors and review articles Intervention(s), exposure(s) - No intervention and exposure Comparator(s)/ control Data from this study will be compared with the similar studies performed on other than Indian Population Context 1. By study settings: (i) Outdoor patients (ii) Indoor patients 2. By case definition: this will be based on clinical or laboratory confirmed diagnosis of cutaneous reactions Outcome(s) Primary outcome Causative drugs for cutaneous reactions in Indian population Secondary outcomes 1. Frequency of distribution of various cutaneous ADRs
2. Frequency of distribution of commonly observed causative drugs for various cutaneous reactions 3. Frequency of distribution of causality analysis categories; severity and preventability assessment; and types of ADR 4. Incidence of cutaneous ADR 5. Incidence of fatal cutaneous adverse reactions and mortality percentage due to cutaneous ADRs 6. Incubation period 7. Associated conditions 8. Complications 9. Cost of management Data extraction, (selection and coding) Data will be extracted from the studies selected by two reviewers independently. Any disagreements will be discussed and resolved by a consensus or a third reviewer. Risk of bias (quality) assessment Quality of reporting of the observational studies will be assessed by the STROBE statement. Appropriate risk assessment tools will be used to assess risk of bias and quality of individual study. That will be done at both the study and outcome level. Strategy for data synthesis a) Data will be extracted and summarized using central tendency measures (ranges, medians or means) and the proportions as provided by the authors. b) Missing data: If outcome data are missing, various approaches such as a worse case scenario will be used. We will perform sensitivity analyses to test the robustness of our imputations. c) Statistical package: SPSS software version 17.0 Subgroup analysis a) Studies will be divided into two groups- One group will include all studies and second group will comprise of studies that have labeled the causative drugs in certain/definite and probable categories only. Primary outcome variable-causative drugs will be compared between the groups. b) Studies will be divided in to the four groups: South Indian, North Indian, West Indian and East Indian based on the study centers and population study to compare the primary outcome variable and if possible for individually for each cutaneous reactions. c) Cutaneous ADRs will be divided in to two groups- severe and non-severe. SJS/TEN, exfoliative dermatitis, drug induced hypersensitivity syndrome (DHS) or drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP) will be considered as serious cutaneous ADRs. The others will be included as non-serious. Commonly observed causative drugs will be compared by odds ratio and Chi-square test between the groups. Dissemination plans
Abstract will be submitted for presentation at an appropriate conference. Manuscript will be submitted for publication to a peer-reviewed journal. Contact details for further information Dr. Tejas K. Patel, Dept. of Pharmacology, GMERS Medical College, Gotri, Vadodara, E-mail: dr.tkp2006@yahoo.co.in M. no: +91 9909105876 Organisational affiliation of the review 1. GMERS Medical College, Gotri, http://gmersmcgv.ac.in/ Review team 1. Dr. Tejas K. Patel, Department of Pharmacology, GMERS Medical College, Gotri, 2. Dr. Sejal Thakkar, Department of Skin & V.D., GMERS Medical College, Gotri, Gujarat, India 3. Dr. D.C. Sharma, Department of Pharmacology, GMERS Medical College, Gotri, Funding sources/sponsors None Conflicts of interest None known Language English Country India Subject index terms cutaneous adverse drug reaction; Skin reaction
Date of registration in PROSPERO : Yet to be done Stage of review at time of this submission StartedCompleted Preliminary searches Yes No Piloting of the study selection process Yes No Formal screening of search results against eligibility criteria Yes No Data extraction No No Risk of bias (quality) assessment No No Data analysis No No Prospective meta-analysis No No