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.

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In clinical research, study results, which are statistically significant are often interpreted as being clinically important. While statistical significance indicates the reliability of the study results, clinical significance reflects its impact on clinical practice. The third article in this series exploring pitfalls in statistical analysis clarifies the importance of differentiating between statistical significance and clinical significance.

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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.

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In biomedical research, we are often interested in quantifying the relationship between an exposure and an outcome. “Odds” and “Risk” are the most common terms which are used as measures of association between variables. In this article, which is the fourth in the series of common pitfalls in statistical analysis, we explain the meaning of risk and odds and the difference between the two.

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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.

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Electronic health record (EHR) is increasingly being implemented in many developing countries. It is the need of the hour because it improves the quality of health care and is also cost-effective. Technologies can introduce some hazards hence safety of information in the system is a real challenge. Recent news of security breaches has put a question mark on this system. Despite its increased usefulness, and increasing enthusiasm in its adoption, not much attention is being paid to the ethical issues that might arise. Securing EHR with an encrypted password is a probable option. The purpose of this article is to discuss the various ethical issues arising in the use of the EHRs and their possible solutions.

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One of the first steps in planning a research study is the choice of study design. The available study designs are divided broadly into two types – observational and interventional. Of the various observational study designs, the descriptive design is the simplest. It allows the researcher to study and describe the distribution of one or more variables, without regard to any causal or other hypotheses. This article discusses the subtypes of descriptive study design, and their strengths and limitations.

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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.

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During the conduct of clinical trials, it is not uncommon to have protocol violations or inability to assess outcomes. This article in our series on common pitfalls in statistical analysis explains the complexities of analyzing results from such trials and highlights the importance of "intention-to-treat" analysis.

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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.

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Agreement between measurements refers to the degree of concordance between two (or more) sets of measurements. Statistical methods to test agreement are used to assess inter-rater variability or to decide whether one technique for measuring a variable can substitute another. In this article, we look at statistical measures of agreement for different types of data and discuss the differences between these and those for assessing correlation.

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In the fourth piece of this series on research study designs, we look at interventional studies (clinical trials). These studies differ from observational studies in that the investigator decides whether or not a participant will receive the exposure (or intervention). In this article, we describe the key features and types of interventional studies.

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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.

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The Nuremberg Code drafted at the end of the Doctor's trial in Nuremberg 1947 has been hailed as a landmark document in medical and research ethics. Close examination of this code reveals that it was based on the Guidelines for Human Experimentation of 1931. The resemblance between these documents is uncanny. It is unfortunate that the authors of the Nuremberg Code passed it off as their original work. There is evidence that the defendants at the trial did request that their actions be judged on the basis of the 1931 Guidelines, in force in Germany. The prosecutors, however, ignored the request and tried the defendants for crimes against humanity, and the judges included the Nuremberg Code as a part of the judgment. Six of ten principles in Nuremberg Code are derived from the 1931 Guidelines, and two of four newly inserted principles are open to misinterpretation. There is little doubt that the Code was prepared after studying the Guidelines, but no reference was made to the Guidelines, for reasons that are not known. Using the Guidelines as a base document without giving due credit is plagiarism; as per our understanding of ethics today, this would be considered unethical. The Nuremberg Code has fallen by the wayside; since unlike the Declaration of Helsinki, it is not regularly reviewed and updated. The regular updating of some ethics codes is evidence of the evolving nature of human ethics.

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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.

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Correlation is a statistical technique which shows whether and how strongly two continuous variables are related. In this article, which is the eighth part in a series on 'Common pitfalls in Statistical Analysis', we look at the interpretation of the correlation coefficient and examine various situations in which the use of technique of correlation may be inappropriate.

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MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression in diverse biological process. They act as intracellular mediators that are necessary for various biological processes. MicroRNAs targeting pathways of human disease provide a new and potential powerful candidate for therapeutic intervention against various pathological conditions. Even though, the information about miRNA biology has significantly enriched but we still do not completely understand the mechanism of miRNA gene regulation. Various groups across the globe and pharmaceutical companies are conducting research and developments to explore miRNA based therapy and build a whole new area of miroRNA therapeutics. Consequently, few miRNAs have entered the preclinical and clinical stage and soon might be available in the market for use in humans.

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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.

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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.

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Early access programs, (EAPs) are adopted by an increasing number of pharma companies due to several benefits offered by these programs. EAPs offer ethical, compliant, and controlled mechanisms of access to investigational drugs outside of the clinical trial space and before the commercial launch of the drug, to patients with life-threatening diseases having no treatment options available. In addition to the development of positive relationships with key opinion leaders (KOL), patients, advocacy groups and regulators, the data captured from the implementation of EAPs supports in the formulation of global commercialization strategies. This white paper outlines various circumstances to be considered for the implementation of EAPs named patient programs, the regulatory landscape, the benefits and challenges associated with implementing these programs and the key considerations for their successful implementation.

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Fraud and misconduct in clinical research is widespread. Good clinical practice is a guideline adopted internationally as standard operating procedure for conduct of clinical research. Despite these guidelines being available, unavailability of internationally harmonized framework for managing research fraud and misconduct makes clinical research a highly vulnerable area to commit fraud. Fraud could be of various types and due to various reasons. Whatever the circumstances be, any fraud should be dealt with strictly and regulations should be in place to prevent its occurrence.

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