Perspectives in Clinical Research最新文献

Background: The 1983 US Orphan Drug Act provided impetus for the development of new therapies for rare diseases. Several studies focused on the number of orphan designations over time. However, very few focused on clinical trials that lead to their approval, particularly for infectious diseases.

Materials and methods: All new drug approvals (orphan and non-orphan) by the US Food and Drug Administration (FDA) from January 2010 to December 31, 2020, were identified and details of approvals were taken from the US-FDA labels and summary reports for each drug. The pivotal trials for each were characterized based on their design. We tested the association of the type of drug approval with respect to the characteristics of trial using Chi-square test and generated crude odds ratios with 95% confidence intervals.

Results: From the total 1122 drugs approved, 84 were for infectious diseases, of which 18 were orphan drugs and 66 were nonorphan. A total of 35 pivotal trials supported 18 orphan drug approvals, while 115 pivotal trials supported 66 nonorphan drugs. The median number of participants enrolled/trial for orphan drugs was 89, while for nonorphan drugs, it was 452 (P < 0.0001). Blinding was done for 13/35 (37%) orphan drugs versus 69/115 (60%) nonorphan drugs (P = 0.029); randomization was done for 15/35 (42%) orphan drugs versus 100/115 (87%) nonorphan drugs (P < 0.0001) and 20/35 (57%) of the orphan drugs got approval in phase II versus 8/115 (6%) of nonorphan drugs (P < 0.00001).

Conclusion: A significant number of orphan drugs get approval based on early phase, nonrandomized, and unblinded with a smaller sample size as compared to nonorphan drugs.

Real-world data, routinely collected from multiple sources outside typical clinical research settings, are useful in conducting real-world studies. Sub-optimal and inconsistent data quality is a challenging issue which should be addressed whilst planning and conducting real-world studies. This brief review discusses the quality aspects of data needed for RWS.

Introduction: Since June 15, 2009, clinical trial registration in the Clinical Trial Registry-India (CTRI) has been made mandatory by the Drugs Controller General of India to improve transparency, accountability, conform to accepted ethical standards and reporting of all relevant results of registered trials. In this study, we planned to evaluate the compliance of Indian and global sponsors with clinical trials conducted in India in terms of reporting of clinical trial results at the CTRI.

Methods: We included trials registered in the CTRI between January 2018 and January 2020. The CTRI and ClinicalTrials.gov registry was thoroughly searched for all completed interventional studies. A year-wise comparative analysis was performed to evaluate the number of clinical trials reporting results in both the registry.

Results: The reporting of completed interventional clinical trial results was 25/112 (22.32%) in year 2018, y, 8/105 (7.6%) in year 2019 and 17/140 (12.14%) in year 2020. There was significantly less reporting of results of Pharmaceutical company sponsored Interventional Studies-Indian at CTRI when compared with ClinicalTrials.gov registry for the year 2019 (odds ratio [OR]-0.17 (95% confidence interval [CI]: 0.08-0.36) and P < 0.0001) and year 2020 (OR-0.45 [95% CI: 0.24-0.82] and P < 0.01). The difference in results reported at CTRI was significantly low for Pharmaceutical company sponsored Interventional Studies-Global only for year 2019 (OR-0.09 [95% CI: 0.005-1.45] and P = 0.04) compared with ClinicalTrials.gov.

Conclusion: There is a need to develop the culture of reporting clinical trial results in CTRI to strengthen the transparency in the research for overall benefit of public, health care professionals, and research community.

Introduction: The institutional ethics committees (IECs) raise queries following protocol reviews. The quality of these queries would be a useful metric to assess how well the IEC executes its fundamental role of protecting participants.

Methods: Queries received after the initial review and replies sent by a single research department were evaluated. A content analysis was done to identify the domains and categories of queries. We categorized these queries as administrative, ethics related, and scientific. The impact of each query in improving the science or safeguarding the rights and safety of research participants (ethics) was evaluated by two authors of this manuscript: one affiliated and the other nonaffiliated to the institute. Kappa statistics were used to evaluate for agreement between the two.

Results: A total of 13 studies (investigator-initiated studies [IISs]: 7 and pharmaceutical industry-sponsored studies [PSSs]: 6) formed the final sample size for analysis. The total number of queries was 364 (IIS: 106 and PSS: 258; P < 0.001). With regard to the categories, we found n = 42 (11.54%) to be irrelevant at that stage of the review process; n = 51 (14.01%) were about information already available which the IEC had missed; n = 67 (18.41%) queries where the IEC needed paraphrasing; n = 50 (13.74%) were entirely relevant with the need for further clarification; and n = 154 (42.31%) had been missed by the investigator during the initial submission. The overall agreement between the affiliated and unaffiliated investigators was just 12.9% (P < 0.001).

Conclusions: We found that approximately 25% of the queries raised by the IEC were redundant. It is our opinion that this redundancy could have been channeled into greater focus on scientific and ethical aspects of the protocol. Ongoing dialog between investigators and ethics committees may help address this. Perspectives between the affiliated and the unaffiliated investigators with regard to the relevance of queries were grossly different.

Objectives: The objective of this study was to analyze antibiotic prescribing patterns in pediatric outpatients in a tertiary care teaching hospital in Eastern India, to identify use of World Health Organization (WHO) access, watch and reserve (AWaRe) antibiotics and to identify rationality of prescribing on the basis of WHO core prescribing indicators.

Materials and methods: Scanned copies of prescriptions were collected from the pediatrics outpatients and antibiotic utilization pattern was analyzed in reference to WHO AWaRe groupings and core prescribing indicators.

Results: Over the 3 months study period, 310 prescriptions were screened. The prevalence of antibiotic use 36.77%. The majority of the 114 children who received antibiotics were males (52.64%, 60) and belonged to 1-5 year age group (49.12%, 56). The highest number of antibiotic prescriptions was from the penicillin class (58, 46.60%) followed by cephalosporin (23.29%) and macrolide (16.54%). Most number of prescribed antibiotics belonged to Access group (63, 47.37%), followed by Watch group (51, 38.35%). Average number of drugs per prescription was 2.66, percentage of encounters with injections were 0.64%. Most of the prescriptions were prescribed using generic name (74.18%, 612), 58.30% (481) of drugs were from WHO Model List of Essential Medicines for children.

Conclusion: If antibiotics are indicated, more number of antibiotics from the Access group may be used for ambulatory children who attend outpatient department of tertiary care hospitals. A simple combination of metrics based on AWaRe groups and core prescribing indicators may eliminate the problem of unnecessary antibiotic prescribing in children and may broaden the antibiotic stewardship opportunities.

The regulatory approval process of the United States Food and Drug Administration and European Union is the most demanding and challenging worldwide. They have the provision of the expedited approval pathways, i.e., "Emergency use authorizations" and "Conditional marketing authorizations," respectively, to give approval to novel therapeutics agents during emergency situations. India, firstly formalized the accelerated pathway named "Accelerated Approval Process" as per the New Drugs and Clinical Trials rule 2019 to address unmet medical needs that was implemented by the Central Drug Standard Control Organization to approve the novel therapeutics agents during COVID-19. Hence, our aim is to understand and compare the different emergency approval processes in the world, their underlined claims and conditions with the list of approved products under this concept. All the information collected and analyzed from different official websites of regulatory bodies. In this review, we have enlightened on all these processes with their few approved products.

A clinical trial is the most foolproof method to evaluate the efficacy of a new intervention. Successful completion of clinical trials depends on the retention of the participants enrolled. Poor participant retention can lead to significant time and cost burden and have potentially adverse biases on the results. A high retention rate of participants is an important criterion for the validity and credibility of randomized controlled clinical trials. Many long-term trials fail due to low retention of study participants. Efforts at participant retention should start even before the first participant is recruited into the study. Retention is not only the responsibility of the investigators but also all other stakeholders in a clinical trial. In recent years, retention materials, participant camps, and introduction of national study coordinators have helped in improving retention. Quality of the relationship developed between the research staff and the study participant is a key factor for success of any trial. In our experience, in the context of resource-challenged low- and middle-income countries, we have found that it is possible to achieve high retention rates, 95%-100%. The rapport built between the investigating team and the participant plays a vital role in retention. In addition, personalized care, including listening to the participant's problems and enabling to contact investigators or study team at any time of the day, has shown benefits in retention.

Purpose/aim: Adverse drug reactions (ADRs) are significantly under-reported worldwide. The aim of this study was to assess the impact of educational interventions (EIs) on knowledge, attitude, and practice (KAP) of hospital resident doctors and faculty members and compare ADR reporting in EI (medical specialties) vs. non-EI (surgical specialties) in these two cadres of doctors.

Materials and methods: This study was a prospective comparative study conducted in two groups (EI and non-EI) in resident doctors and faculty members working at a tertiary care hospital. EI group (medical specialties) were provided with EI to increase awareness about ADR reporting, whereas in non-EI group (surgical specialties), no EI was provided and they served as control. Respondents were asked to fill a pretest questionnaire followed by interactive EI in EI group and posttest questionnaire in both groups. The impact of EI among respondents was evaluated by their response to questionnaire and number of ADRs reported after intervention.

Results: Total (n = 202) respondents were enrolled in the study. The number of resident doctors and faculty members in each group were (n = 101 [50%]). Overall, (n = 100 [49.5%]) were from the medical and (n = 102 [50.5%]) from surgical specialty. Post-EI period, there was statistically significant improvement in KAP domains.

Conclusion: Our study serves as credible evidence that through EI; statistically significant improvement in KAP of resident doctors and faculty members in both medical and surgical specialties toward ADR reporting and existing pharmacovigilance system can be achieved.

Background: Dabigatran is the first oral direct thrombin inhibitor which is endorsed by Food and Drug Administration in the prevention of embolic events in patients with nonvalvular atrial fibrillation. Suitable dose of the drug for the patient is selected based on CHA2DS2-VASc score and HAS-BLED score.

Aim: To determine and compare the risk of occurrence of stroke and bleeding after the initiation of dabigatran therapy in patients prescribed with this drug.

Methods: Patients with more than 18 years who were prescribed with dabigatran during 2017-2019 in a tertiary care hospital were selected for the study. Most of the patient's prescriptions contained an antiplatelet, so a comparison was made between the clinical outcomes of patients given with dabigatran alone and dabigatran with an antiplatelet because antiplatelet can have effects on the safety as well as efficacy profile of dabigatran.

Results: Out of 75 patients enrolled in the study, 42 patients were in the dabigatran with the antiplatelet group and 33 were in the dabigatran alone group. In both the groups, there was a significant reduction in CHA₂DS₂-VASc score, i.e., 2.58 ± 1.32-1.94 ± 1.21 in dabigatran-treated patients within 6 months, and the score was lowered from 3.76 ± 1.22 to 2.92 ± 1.22 in other groups. The mean value of the HAS-BLED score of dabigatran was reduced from 1.15 ± 0.83 to 0.84 ± 0.78 and that of dabigatran with antiplatelet group from 2.10 ± 0.94 to 1.74 ± 0.92.

Conclusion: It was observed that within 6 months, both the treatment groups showed a reduction in the risk scores. The dabigatran group had lower background risks of stroke and bleeding in comparison to the dabigatran plus antiplatelet group.