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  Most popular articles (Since October 20, 2010)

 
 
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BIOSTATISTICS
Intention-to-treat concept: A review
Sandeep K Gupta
July-September 2011, 2(3):109-112
DOI:10.4103/2229-3485.83221  PMID:21897887
Randomized controlled trials often suffer from two major complications, i.e., noncompliance and missing outcomes. One potential solution to this problem is a statistical concept called intention-to-treat (ITT) analysis. ITT analysis includes every subject who is randomized according to randomized treatment assignment. It ignores noncompliance, protocol deviations, withdrawal, and anything that happens after randomization. ITT analysis maintains prognostic balance generated from the original random treatment allocation. In ITT analysis, estimate of treatment effect is generally conservative. A better application of the ITT approach is possible if complete outcome data are available for all randomized subjects. Per-protocol population is defined as a subset of the ITT population who completed the study without any major protocol violations.
  15,299 4,377 225
CLINICAL DATA MANAGEMENT
Basics of case report form designing in clinical research
Shantala Bellary, Binny Krishnankutty, MS Latha
October-December 2014, 5(4):159-166
DOI:10.4103/2229-3485.140555  PMID:25276625
Case report form (CRF) is a specialized document in clinical research. It should be study protocol driven, robust in content and have material to collect the study specific data. Though paper CRFs are still used largely, use of electronic CRFs (eCRFS) are gaining popularity due to the advantages they offer such as improved data quality, online discrepancy management and faster database lock etc. Main objectives behind CRF development are preserving and maintaining quality and integrity of data. CRF design should be standardized to address the needs of all users such as investigator, site coordinator, study monitor, data entry personnel, medical coder and statistician. Data should be organized in a format that facilitates and simplifies data analysis. Collection of large amount of data will result in wasted resources in collecting and processing it and in many circumstances, will not be utilized for analysis. Apart from that, standard guidelines should be followed while designing the CRF. CRF completion manual should be provided to the site personnel to promote accurate data entry by them. These measures will result in reduced query generations and improved data integrity. It is recommended to establish and maintain a library of templates of standard CRF modules as they are time saving and cost-effective. This article is an attempt to describe the methods of CRF designing in clinical research and discusses the challenges encountered in this process.
  14,582 1,958 4
QUALITY
Good clinical practice regulatory inspections: Lessons for Indian investigator sites
R Marwah, K Van de Voorde, J Parchman
October-December 2010, 1(4):151-155
DOI:10.4103/2229-3485.71776  PMID:21350732
Regulatory inspections are important to evaluate the integrity of the data submitted to health authorities (HAs), protect patient safety, and assess adequacy of site/sponsor quality systems to achieve the same. Inspections generally occur after submission of data for marketing approval of an investigational drug. In recent years, there has been a significant increase in number of inspections by different HAs, including in India. The assessors/inspectors generally do a thorough review of site data before inspections. All aspects of ICH-GCP, site infrastructure, and quality control systems are assessed during the inspection. Findings are discussed during the close out meeting and a detailed inspection report issued afterward, which has to be responded to within 15-30 days with effective Corrective and Preventive Action Plan (CAPA). Protocol noncompliance, inadequate/inaccurate records, inadequate drug accountability, informed consent issues, and adverse event reporting were some of the most common findings observed during recent Food and Drug Administration (FDA) inspections. Drug development is being increasingly globalized and an increased number of patients enrolled in studies submitted as part of applications come from all over the world including India. Because of the steep increase in research activity in the country, inexperienced sites, and more stakeholders, increased efforts will be required to ensure continuous quality and compliance. HAs have also made clear that enforcement will be increased and be swift, aggressive, and effective.
  10,637 675 2
STATISTICS
Survival analysis in clinical trials: Basics and must know areas
Ritesh Singh, Keshab Mukhopadhyay
October-December 2011, 2(4):145-148
DOI:10.4103/2229-3485.86872  
Many clinical trials involve following patients for a long time. The primary event of interest in those studies is death, relapse, adverse drug reaction or development of a new disease. The follow-up time for the study may range from few weeks to many years. A different set of statistical procedures are employed to analyze the data, which involves time to event an analysis. It is a very useful tool in clinical research and provides invaluable information about an intervention. This article introduces the researcher to the different tools of survival analysis.
  9,379 1,929 14
ORIGINAL ARTICLES
Effects of botropase on clotting factors in healthy human volunteers
Ashok K Shenoy, KV Ramesh, Mukta N Chowta, Prabha M Adhikari, UP Rathnakar
April-June 2014, 5(2):71-74
DOI:10.4103/2229-3485.128024  PMID:24741483
Objective: To evaluate the effects of botropase on various clotting factors in human volunteers. Materials and Methods: It was a prospective open label study conducted on human healthy volunteers. After the baseline screening, subjects fulfilling inclusion criteria were enrolled. On the study day, 1 ml of botropase was administered intravenously and after an hour same dose of botropase (1 ml) was given by intramuscular (IM) route. The efficacy and safety parameters were monitored up to 72 h from the time of intravenous (IV) administration. Results: A total of 15 volunteers, belonging to 24-35 years of age were included in the study. Botropase significantly reduced the plasma level of fibrinogen and fibrin degradation products after 5 min of IV administration (P < 0.05). In addition, factor X was observed to reduce constantly by botropase administration suggesting enhanced turnover between 5 and 20 min of IV administration. Although botropase reduced clotting and bleeding time in all the volunteers, the data remains to be statistically insignificant. Conclusion: Present study demonstrated the safety and efficacy of botropase in human healthy volunteers. The study has shown that it is a factor X activator and reduces effectively clotting and bleeding time.
  10,461 346 3
MEDICAL WRITING
Plagiarism: Why is it such a big issue for medical writers?
Natasha Das, Monica Panjabi
April-June 2011, 2(2):67-71
DOI:10.4103/2229-3485.80370  PMID:21731858
Plagiarism is the wrongful presentation of somebody else's work or idea as one's own without adequately attributing it to the source. Most authors know that plagiarism is an unethical publication practice. Yet, it is a serious problem in the medical writing arena. Plagiarism is perhaps the commonest ethical issue plaguing medical writing. In this article, we highlight the different types of plagiarism and address the issues of plagiarism of text, plagiarism of ideas, mosaic plagiarism, self-plagiarism, and duplicate publication. An act of plagiarism can have several repercussions for the author, the journal in question and the publication house as a whole. Sometimes, strict disciplinary action is also taken against the plagiarist. The article cites examples of retraction of articles, suspension of authors, apology letters from journal editors, and other such actions against plagiarism.
  7,155 1,328 9
BIOSTATISTICS
What to use to express the variability of data: Standard deviation or standard error of mean?
Mohini P Barde, Prajakt J Barde
July-September 2012, 3(3):113-116
DOI:10.4103/2229-3485.100662  PMID:23125963
Statistics plays a vital role in biomedical research. It helps present data precisely and draws the meaningful conclusions. While presenting data, one should be aware of using adequate statistical measures. In biomedical journals, Standard Error of Mean (SEM) and Standard Deviation (SD) are used interchangeably to express the variability; though they measure different parameters. SEM quantifies uncertainty in estimate of the mean whereas SD indicates dispersion of the data from mean. As readers are generally interested in knowing the variability within sample, descriptive data should be precisely summarized with SD. Use of SEM should be limited to compute CI which measures the precision of population estimate. Journals can avoid such errors by requiring authors to adhere to their guidelines.
  6,863 1,360 11
QUALITY
Good documentation practice in clinical research
Chitra Bargaje
April-June 2011, 2(2):59-63
DOI:10.4103/2229-3485.80368  PMID:21731856
One of the most common inspection findings in investigator site inspections is lack of reliable, accurate and adequate source documentation. This also happens to be the most common pitfall identified during sponsor audits. The importance of good documentation practice needs to be emphasized to investigator sites to ensure that the study results are built on the foundation of credible and valid data. This article focuses on the key principles of good documentation practice and offers suggestions for improvement.
  6,596 1,307 4
RESEARCH METHODOLOGY
Patient-reported outcomes: A new era in clinical research
Prasanna R Deshpande, Surulivel Rajan, B Lakshmi Sudeepthi, CP Abdul Nazir
October-December 2011, 2(4):137-144
DOI:10.4103/2229-3485.86879  
Now-a-days there is significant discussion about patient-reported outcomes (PRO) in medical world. The following article covers almost all the areas of PRO including-their importance, important concepts for understanding of PRO, significance, ideal properties, types, development and evaluation of PRO instruments. It is useful for physicians, pharmacists and patients for the assessment and improvement of the therapy.
  5,642 1,432 74
PHARMACOVIGILANCE
Pharmacovigilance for clinical trials in India: Current practice and areas for reform
Ballari Brahmachari, Melanie Fernandes, Arun Bhatt
April-June 2011, 2(2):49-53
DOI:10.4103/2229-3485.80366  PMID:21731854
Keeping in mind India's increasing participation in multinational trials, this article explores potential areas of Indian pharmacovigilance, requiring reform and provides recommendations for building a robust safety reporting system. Internal discrepancies exist between Schedule Y and Central Drugs Standard Control Organisation approval letter regarding what to report. Schedule Y's silence on expedited reporting requirements creates confusion for Indian sites that are part of multinational trial. Not allowing waiver for serious adverse events that are protocol specified or are study endpoints, along with lack of emphasis on causality as reporting criteria, adds substantial burden of uninformative cases for regulatory review. Despite global focus on Development Safety Update Report, Indian regulators are not yet insistent on real-time update of a drug's cumulative safety profile. Issues like reporting requirements for generic trials, pregnancy reporting and lenient timeline for death/life-threatening events need attention. Finally, the need to formulate an all-encompassing pharmacovigilance guideline for India, in sync with global practice cannot be overemphasized.
  5,467 1,350 1
CLINICAL RESEARCH METHODOLOGY
Phase 0 clinical trials in oncology new drug development
Umesh Chandra Gupta, Sandeep Bhatia, Amit Garg, Amit Sharma, Vaibhav Choudhary
January-March 2011, 2(1):13-22
DOI:10.4103/2229-3485.76285  PMID:21584177
Research focus of pharmaceutical industry has expanded to a larger extent in last few decades putting many more new molecules, particularly targeted agents, for the clinical development. On the other hand, researchers are facing serious challenges due to high failure rates of new molecules in clinical studies. The United States Food and Drug Administration (FDA) in combination with academia and industry experts identified many factors responsible for failures of new molecules, and with a vision of taking traditional drug development model toward an innovative paradigm shift, issued regulatory guidance on conduct of exploratory investigational new drug (exploratory IND) studies, often called as phase 0 clinical trials, requiring reduced preclinical testing, which has special relevance to life-threatening diseases such as cancer. Phase 0 trials, utilizing much lower drug doses, provide an opportunity to explore the clinical behavior of new molecules very early in the drug development pathway, helping to identify the promising candidates and eliminating non-promising molecules, thus improving the efficiency of overall drug development with significant savings of resources. Being non-therapeutic in nature, these studies, however, pose certain ethical challenges requiring careful study designing and informed consent process. This article reviews the insights and perspectives for the feasibility, utility, planning, designing and conduct of phase 0 clinical trials, in addition to ethical issues and industrial perspective focused at oncology new drug development.
  5,353 1,427 3
LETTER TO EDITOR
Censoring in survival analysis: Potential for bias
Priya Ranganathan, CS Pramesh
January-March 2012, 3(1):40-40
DOI:10.4103/2229-3485.92307  
  6,179 453 7
QUALITY
Quality assurance: Importance of systems and standard operating procedures
Kishu Manghani
January-March 2011, 2(1):34-37
PMID:21584180
It is mandatory for sponsors of clinical trials and contract research organizations alike to establish, manage and monitor their quality control and quality assurance systems and their integral standard operating procedures and other quality documents to provide high-quality products and services to fully satisfy customer needs and expectations. Quality control and quality assurance systems together constitute the key quality systems. Quality control and quality assurance are parts of quality management. Quality control is focused on fulfilling quality requirements, whereas quality assurance is focused on providing confidence that quality requirements are fulfilled. The quality systems must be commensurate with the Company business objectives and business model. Top management commitment and its active involvement are critical in order to ensure at all times the adequacy, suitability, effectiveness and efficiency of the quality systems. Effective and efficient quality systems can promote timely registration of drugs by eliminating waste and the need for rework with overall financial and social benefits to the Company.
  5,564 1,058 -
EDITORIAL
Electronic informed consenting: A boon to modernize consenting process
Premnath Shenoy
October-December 2015, 6(4):173-174
DOI:10.4103/2229-3485.167091  PMID:26623385
  758 5,617 1
Taking the 'Risk' out of risk-based monitoring
Ashwaria Gupta
October-December 2013, 4(4):193-195
DOI:10.4103/2229-3485.120165  PMID:24312884
  1,170 5,182 -
HISTORY
Evolution of clinical research: A history before and beyond james lind
Arun Bhatt
January-March 2010, 1(1):6-10
PMID:21829774
The evolution of clinical research traverses a long and fascinating journey. From the first recorded trial of legumes in biblical times to the first randomized controlled of trial of streptomycin in 1946, the history of clinical trial covers a wide variety of challenges - scientific, ethical and regulatory. The famous 1747 scurvy trial conducted by James Lind contained most elements of a controlled trial. The UK Medical Research Council's (MRC) trial of patulin for common cold in 1943 was the first double blind controlled trial. This paved the way for the first randomized control trial of streptomycin in pulmonary tuberculosis carried out in 1946 by MRC of the UK. This landmark trial was a model of meticulousness in design and implementation, with systematic enrolment criteria and data collection compared with the ad hoc nature of other contemporary research. Over the years, as the discipline of controlled trials grew in sophistication and influence, the streptomycin trial continues to be referred to as ground breaking. The ethical advances in human protection include several milestones - Nuremberg Code, Declaration of Helsinki, Belmont Report, and 1996, International Conference on Harmonization Good Clinical Practice guidance. In parallel to ethical guidelines, clinical trials started to become embodied in regulation as government authorities began recognizing a need for controlling medical therapies in the early 20th century. As the scientific advances continue to occur, there will be new ethical and regulatory challenges requiring dynamic updates in ethical and legal framework of clinical trials.
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EDITORIAL
Comparisons are odious
Viraj Suvarna
October-December 2014, 5(4):143-144
DOI:10.4103/2229-3485.140540  PMID:25276621
  1,015 4,959 -
MONITORING
Hybrid approaches to clinical trial monitoring: Practical alternatives to 100% source data verification
Sourabh De
July-September 2011, 2(3):100-104
DOI:10.4103/2229-3485.83226  PMID:21897885
For years, a vast majority of clinical trial industry has followed the tenet of 100% source data verification (SDV). This has been driven partly by the overcautious approach to linking quality of data to the extent of monitoring and SDV and partly by being on the safer side of regulations. The regulations however, do not state any upper or lower limits of SDV. What it expects from researchers and the sponsors is methodologies which ensure data quality. How the industry does it is open to innovation and application of statistical methods, targeted and remote monitoring, real time reporting, adaptive monitoring schedules, etc. In short, hybrid approaches to monitoring. Coupled with concepts of optimum monitoring and SDV at site and off-site monitoring techniques, it should be possible to save time required to conduct SDV leading to more available time for other productive activities. Organizations stand to gain directly or indirectly from such savings, whether by diverting the funds back to the R&D pipeline; investing more in technology infrastructure to support large trials; or simply increasing sample size of trials. Whether it also affects the work-life balance of monitors who may then need to travel with a less hectic schedule for the same level of quality and productivity can be predicted only when there is more evidence from field.
  4,838 759 8
ETHICS
Ethics committees in India: Facing the challenges!
Rashmi Kadam, Shashikant Karandikar
April-June 2012, 3(2):50-56
DOI:10.4103/2229-3485.96444  
The past few years have seen a tremendous rise in the number of clinical trials conducted in India. This is been attributed to the huge patient population, genetic diversity, and rich technical pool in our country. However, the economical upsurge in the clinical trial industry has also caused concerns pertaining to the efficiency of the Regulatory Agencies and Ethics Committees (EC). The EC plays an important role in the regulation of clinical research at the local level. However, it is seen that many ECs are oblivious to their roles and responsibilities. It is reported that ECs lack standard operating procedures, do not have a proper composition or adequate representation, thus affecting their functions in regulating clinical research. Moreover, ECs seem to function in isolation, as self-sufficient bodies, having no communication with the regulatory agency or other ECs. This brings forth the need for ECs to come together and share their experiences and observations, with the aim of updating themselves and refining their functions. Efforts also need to be focused on capacity building, centralized registration of ECs, and bringing an oversight mechanism in place. The Ethics Committees in India need to work in close association with forums such as the Forum for Ethics Review Committees in India and the Forum for Ethical Review Committees in Asia Pacific, in an effort towards empowering themselves.
  4,674 847 15
ORIGINAL ARTICLE
An evaluation of knowledge, attitude, and practice of adverse drug reaction reporting among prescribers at a tertiary care hospital
Chetna K Desai, Geetha Iyer, Jigar Panchal, Samidh Shah, RK Dikshit
October-December 2011, 2(4):129-136
DOI:10.4103/2229-3485.86883  
Objectives: Spontaneous reporting is an important tool in pharmacovigilance. However, its success depends on cooperative and motivated prescribers. Under-reporting of adverse drug reactions (ADRs) by prescribers is a common problem. The present study was undertaken to evaluate the knowledge, attitude, and practices (KAP) regarding ADR reporting among prescribers at the Civil Hospital, Ahmedabad, to get an insight into the causes of under-reporting of ADRs. Materials and Methods: A pretested KAP questionnaire comprising of 15 questions (knowledge 6, attitude 5, and practice 4) was administered to 436 prescribers. The questionnaires were assessed for their completeness (maximum score 20) and the type of responses regarding ADR reporting. Microsoft Excel worksheet (Microsoft Office 2007) and Chi-Square test were used for statistical analysis. Results: A total of 260 (61%) prescribers completed the questionnaire (mean score of completion 18.04). The response rate of resident doctors (70.7%) was better than consultants (34.5%) (P < 0.001). ADR reporting was considered important by 97.3% of the respondents; primarily for improving patient safety (28.8%) and identifying new ADRs (24.6%). A majority of the respondents opined that they would like to report serious ADRs (56%). However, only 15% of the prescribers had reported ADRs previously. The reasons cited for this were lack of information on where (70%) and how (68%) to report and the lack of access to reporting forms (49.2%). Preferred methods for reporting were e-mail (56%) and personal communication (42%). Conclusion: The prescribers are aware of the ADRs and the importance of their reporting. However, under reporting and lack of knowledge about the reporting system are clearly evident. Creating awareness about ADR reporting and devising means to make it easy and convenient may aid in improving spontaneous reporting.
  4,335 1,121 7
QUALITY
Quality of clinical trials: A moving target
Arun Bhatt
October-December 2011, 2(4):124-128
DOI:10.4103/2229-3485.86880  
Quality of clinical trials depends on data integrity and subject protection. Globalization, outsourcing and increasing complexicity of clinical trials have made the target of achieving global quality challenging. The quality, as judged by regulatory inspections of the investigator sites, sponsors/contract research organizations and Institutional Review Board, has been of concern to the US Food and Drug Administration, as there has been hardly any change in frequency and nature of common deficiencies. To meet the regulatory expectations, the sponsors need to improve quality by developing systems with specific standards for each clinical trial process. The quality systems include: personnel roles and responsibilities, training, policies and procedures, quality assurance and auditing, document management, record retention, and reporting and corrective and preventive action. With an objective to improve quality, the FDA has planned new inspection approaches such as risk-based inspections, surveillance inspections, real-time oversight, and audit of sponsor quality systems. The FDA has partnered with Duke University for Clinical Trials Transformation Initiative, which will conduct research projects on design principles, data quality and quantity including monitoring, study start-up, and adverse event reporting. These recent initiatives will go a long way in improving quality of clinical trials.
  4,093 1,143 4
ORIGINAL ARTICLES
Prevalence of self-medication practices and its associated factors in Urban Puducherry, India
Kalaiselvi Selvaraj, Ganesh Kumar S, Archana Ramalingam
January-March 2014, 5(1):32-36
DOI:10.4103/2229-3485.124569  PMID:24551585
Background and Objectives: Self medication is an important concern for health authorities at global level. This study was aimed to find the prevalence of self medication for allopathic drugs and associated factors among households of urban community. This study was also aimed at assessing the attitude of respondents who had experienced self-medication. Materials and Methods: This cross-sectional study was done in field practice area attached to a medical institution in urban Puducherry. A total of 352 subjects from 124 households were selected by random sampling. With pretested interview schedule, information regarding self-medication use in the past three months and associated sociodemographic factors, purpose, source of drug procurement, attitude toward self-medication use were collected. Results: Prevalence of self-medication was found to be 11.9%. Males, age >40 years and involving in moderate level activity of occupation, were found to be significantly associated with higher self-medication usage (P < 0.05). Fever (31%), headache (19%), and abdominal pain (16.7%) are most common illnesses where self-medication is being used. Telling the symptoms to pharmacist (38.1%) was the commonest method adopted to procure drugs by the users. Majority of the self-medication users expressed that self-medication is harmless (66.6%) and they are going to use (90%) and advice others also (73.8%) to use self-medication drugs. Conclusion: Self-medication is an important health issue in this area. Health education of the public and regulation of pharmacies may help in limiting the self-medication practices.
  4,333 773 5
REGULATORY
Regulations and guidelines governing stem cell based products: Clinical considerations
Bobby George
July-September 2011, 2(3):94-99
DOI:10.4103/2229-3485.83228  PMID:21897884
The use of stem cells as medicines is a promising and upcoming area of research as they may be able to help the body to regenerate damaged or lost tissue in a host of diseases like Parkinson's, multiple sclerosis, heart disease, liver disease, spinal cord damage, cancer and many more. Translating basic stem cell research into routine therapies is a complex multi-step process which entails the challenge related to managing the expected therapeutic benefits with the potential risks while complying with the existing regulations and guidelines. While in the United States (US) and European Union (EU) regulations are in place, in India, we do not have a well-defined regulatory framework for "stem cell based products (SCBP)". There are several areas that need to be addressed as it is quite different from that of pharmaceuticals. These range from establishing batch consistency, product stability to product safety and efficacy through pre-clinical, clinical studies and marketing authorization. This review summarizes the existing regulations/guidelines in US, EU, India, and the associated challenges in developing SCBP with emphasis on clinical aspects.
  4,145 869 12
EDITORIAL
Non-inferiority and equivalence trials: Need for a standardized process
Suresh Keshav Bowalekar
October-December 2011, 2(4):115-118
DOI:10.4103/2229-3485.86868  
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RESEARCH ETHICS
Readability and comprehensibility of informed consent forms for clinical trials
Anvita Pandiya
July-September 2010, 1(3):98-100
PMID:21814628
The signed informed consent form provides documentary evidence that the patient has given informed consent to participate in a clinical trial and that the patient has been given the requisite information. However, this document must not only provide the necessary information, it must also be provided in a way that can be understood by the patient. Non conclusive information suggests that research participants frequently may not understand the information presented during the informed consent procedure. Comprehension requires that the patient be able to understand the information presented and have the time and opportunity to read, evaluate and consider the information presented. A shortened Informed Consent Form, with information that a reasonable person would want to understand along with specific information that the person wants in particular would be a good option to improve understanding or comprehensibility. Additional informational meetings with a qualified person like a counselor could help in comprehension. Questionnaires designed to test comprehension of patient, peer review, patient writing the salient features could help evaluate the comprehensibility of the Informed Consent Form.
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