An analysis of deficiencies in the data of interventional drug trials registered with Clinical Trials Registry - India

Background Clinical Trials Registry - India (CTRI) was established in July 2007 and today hosts thousands of trials, a significant fraction of them registered in the last couple of years. We wished to undertake an up-to-date analysis of specific fields of the registered trials. In doing so we discovered problems with the quality of the data, which we describe in this paper. Methods We downloaded CTRI records and reformatted the data into an SQLite database, which we then queried. We also accessed ClinicalTrials.gov records as needed. Results We discovered various categories of problems with the data in the CTRI database, including (1) a lack of clarity in the classification of Types of Study, (2) internal inconsistencies, (3) incomplete or non-standard information, (4) missing data, (5) variations in names or classification, and (6) incomplete or incorrect details of ethics committees. For most of these problems, error rates have been calculated, over time. Most were found to be in single digits, although others were significantly higher. We suggest how data quality in future editions of CTRI could be improved, including (1) a more elaborate and structured way of classifying the Type of Study, (2) the use of logic rules to prevent internal inconsistencies, (3) less use of free text fields and greater use of drop-down menus, (4) more fields to be made compulsory, (5) the pre-registration of individuals’ and organizations’ names and their subsequent selection from drop-down menus while registering a trial, and (6) more information about each ethics committee, including (a) its address and (b) linking the name of the trial site to the relevant ethics committee. As we discuss problems with the data of specific fields, we also examine — where possible — the quality of the data in the corresponding fields in ClinicalTrials.gov, the largest clinical trial registry in the world. Conclusions It is a scientific and ethical obligation to correctly record all information pertaining to each trial run in India. CTRI is a valuable database that has proved its worth in terms of improving the record of trials in the country. The suggestions made herein would improve it further. Electronic supplementary material The online version of this article (10.1186/s13063-019-3592-0) contains supplementary material, which is available to authorized users.

Gender Both

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[1] are at least 18 years of age at the time of informed consent.
[2] are able to read, understand, and give documented (electronic or paper signature) informed consent.
[3] have a diagnosis of AD at least 12 months prior to screening, as defined by the American Academy of Dermatology: Guidelines of care for the management of AD; Section 1. Diagnosis and assessment of atopic dermatitis [4] have moderate to severe AD, including all of the following: a. Eczema Area and Severity Index (EASI) score ?16 at screening (Visit 1) and at randomization (Visit 2) b. IGA score of ?3 at screening (Visit 1) and at randomization (Visit 2) c. ?10% of BSA involvement at screening (Visit 1) and at randomization(Visit 2).
[5] have a documented history by a physician and/or investigator of inadequate response to existing topical medications within 6 months preceding screening,or history of intolerance to topical therapy as defined by at least 1 of the following: a. inability to achieve good disease control defined as mild disease or better(e.g., IGA ?2) after use of at least a medium potency TCS for at least 4 weeks, or for the maximum duration recommended by the product prescribing information (e.g., 14 days for super-potent TCS), whichever is shorter. Topical corticosteroids may be used with or without TCNIs. b. Patients who failed systemic therapies intended to treat AD within 6 months preceding screening, such as cyclosporine, methotrexate, azathioprine, mycophenolate mofetil will also be considered as a surrogate for having inadequate response to topical therapy. c. documented history of clinically significant adverse reactions with the use of TCS such as skin atrophy, allergic reactions, systemic effects that in the opinion of the investigator outweigh the benefits of retreatment.
[6] agree to discontinue use of the following excluded medications/treatments for at least 4 weeks prior to randomization (Visit 2) and throughout the study: a. systemic corticosteroids and leukotriene inhibitors b. systemic immunomodulators, including, but not limited to, cyclosporine,methotrexate, mycophenolate mofetil, and azathioprine c. sedating antihistamines, including, but not limited to, alimemazine, chlorphenamine, clemastine, cyproheptadine, diphenhydramine, hydroxyzine, ketotifen, and promethazine Note: Patients may use newer, less sedating antihistamines (e.g.,fexofenadine, loratadine, cetirizine). d. any other systemic therapy used to treat AD or symptoms of AD(approved or off-label use) e. phototherapy, includes therapeutic phototherapy (psoralen plus ultraviolet-A, ultraviolet-B), excimer laser as well as self-treatment with tanning beds.
[7] agree to discontinue use of the following excluded medications for at least 2 weeks prior to randomization (Visit 2) and throughout the study: a. TCS or topical immune modulators (e.g., tacrolimus or pimecrolimus) b. Topical phosphodiesterase type 4 (PDE-4) inhibitor (crisaborole) c. Topical JAK inhibitor (e.g., tofacitinib or ruxolitinib) and/or any other page 6 / 11 investigative topical treatments.
[8] have applied emollients daily for at least 14 days prior to randomization and agree to use emollient daily throughout the treatment period.
[9] Patients who are receiving chronic treatments to improve sleep should be on a stable dose for at least 2 weeks prior to screening as determined by the investigator. Sedating antihistamines (see above) are not permitted.
[10] are male or nonpregnant, nonbreastfeeding female patients,except: a. Male patients must agree to use 2 forms of birth control (1 must be highly effective, see below) while engaging in sexual intercourse with female partners of childbearing potential while enrolled in the study and for at least 4 weeks following the last dose of investigational product.
b. Female patients of childbearing potential must agree to use 2 forms of birth control, when engaging in sexual intercourse with a male partner while enrolled in the study and for at least 4 weeks following the last dose of investigational product.

Exclusion Criteria
Exclusion Criteria

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[1] are currently experiencing or have a history of other concomitant skin conditions (e.g., psoriasis or lupus erythematosus) that would interfere with evaluations of the effect of study medication on AD.
[2] patients who, in the opinion of the investigator, are currently experiencing or have a history of erythrodermic, refractory, or unstable skin disease that requires frequent hospitalizations and/or intravenous treatment for skin infections that may interfere with participation in the study.
[3] a history of eczema herpeticum within 12 months prior to screening.
[4] a history of 2 or more episodes of eczema herpeticum in the past.
[5] patients who are currently experiencing a skin infection that requires treatment, or is currently being treated, with topical or systemic antibiotics.
[6] have any serious concomitant illness that is anticipated to require the use of systemic corticosteroids or otherwise interfere with study participation or require active frequent monitoring (e.g., unstable chronic asthma).
b. received prior treatment with any oral JAK inhibitor (e.g., tofacitinib,ruxolitinib) c. received any parenteral corticosteroid administered by intramuscular or intravenous injection within 2 weeks prior to study entry (Visit 1) or within 6 weeks prior to planned randomization (Visit 2) or are anticipated to require parenteral injection of corticosteroids during the study.
d. have had an intra-articular corticosteroid injection within 2 weeks prior to study entry (Visit 1) or within 6 weeks prior to planned randomization (Visit 2).
[8] are largely or wholly incapacitated permitting little or no self-care, such as page 7 / 11 being bedridden.
[9] have uncontrolled arterial hypertension characterized by a repeated systolic blood pressure >160 mm Hg or diastolic blood pressure >100 mm Hg in a seated position.
[10] have had any major surgery within 8 weeks prior to screening or will require major surgery during the study that, in the opinion of the investigator in consultation with Lilly or its designee, would pose an unacceptable risk to the patient.
[11] are immunocompromised and, in the opinion of the investigator, at an unacceptable risk for participating in the study.
[12] have experienced any of the following within 12 weeks of screening: venous thromboembolic event (VTE), myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage III/IV heart failure.
[ did not receive appropriate and documented prophylaxis for TB.
f. evidence of active TB or have previously had evidence of active TB and did not receive appropriate and documented treatment. g. clinically serious infection or received intravenous antibiotics for an infection, within the past 4 weeks of randomization. h. any other active or recent infection within 4 weeks of randomization that, in the opinion of the investigator, would pose an unacceptable risk to the patient if participating in the study.
[17] have been exposed to a live vaccine within 12 weeks prior to planned randomization or are expected to need/receive a live vaccine during the course of the study (with the exception of herpes zoster vaccination).
[18] have a history of chronic alcohol abuse, IV drug abuse, or other illicit drug abuse within the 2 years prior to screening.
[19] presence of significant uncontrolled neuropsychiatric disorder, are clinically judged by the investigator to be at risk for suicide, or have a "yes" answer to any of the following: a. Question 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) on the "Suicidal Ideation" portion of the Columbia Suicide Severity Rating Scale (C-SSRS) or b. Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the "Suicidal Ideation" portion of the C-SSRS or c. Any of the suicide-related behaviors (actual attempt, interrupted attempt, aborted attempt, preparatory act or behavior) on the "Suicidal Behavior" portion of the C-SSRS;and the ideation or behavior occurred within 2 months prior to Visit 1.
[20] have donated more than a single unit of blood within 4 weeks prior to screening or intend to donate blood during the course of the study.
[21] are unable or unwilling to make themselves available for the duration of the study and/or are unwilling to follow study restrictions/procedures, including use of data collection devices.
[22] are currently enrolled in any other clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study.
[23] have participated within the last 30 days in a clinical study involving an investigational product. If the previous investigational product has a long half-life (2 weeks or longer), at least 3 months or 5 half-lives (whichever is longer) should have passed.
[24] have previously been randomized in this study or any other study investigating baricitinib.
[25] are investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
[26] are Lilly or Incyte employees or their designee.

Brief Summary
Atopic dermatitis (AD) is a pruritic, chronic or chronically relapsing, highly symptomatic inflammatory skin disease characterized by excessive T cell activation leading to significant skin infiltration by T cells and dendritic cells Clinical studies have established that baricitinib is effective in autoimmune/autoinflammatory diseases involving the joints, kidneys, and skin. Baricitinib was effective at reducing swollen and tender joints in patients with rheumatoid page 10 / 11