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Real-world evidence (RWE) is clinical evidence on a medical product's safety and efficacy that is generated using real-world data (RWD) resulting from routine healthcare delivery. There are several sources of RWD, including electronic health records (EHRs), registries, claims/billing data, and patient-generated data, as well as those from mobile health applications and wearable devices. Real-world data from these sources can be collected and analysed through different study designs such as prospective and retrospective cohort studies, case–control studies, and pragmatic clinical trials. Real-world evidence in the form of post-marketing surveillance has been extensively used to generate pharmacovigilance data. Of late, it has been realised that, apart from safety, RWE has additional applications in different stages of the drug approval cycle, and can be used to optimize the design of randomised controlled trials (RCTs). There has been an increasing awareness and acceptance of RWE from different stakeholders, including physicians, pharmaceutical companies, payers, regulators, and patients. Several regulatory authorities have also created frameworks and guidelines for efficient harnessing of RWE while acknowledging several challenges in RWD collection and analysis. The purpose of this review is to offer an outline of the current information on RWE, its advantages and disadvantages, as well as the associated challenges and ways to overcome them, while also throwing some light on the future of RWE. [ABSTRACT FROM AUTHOR]

Background & objectives: Artificial intelligence (AI) and machine learning (ML) have shown promising results in cancer diagnosis in validation tests involving retrospective patient databases. This study was aimed to explore the extent of actual use of AI/ML protocols for diagnosing cancer in prospective settings. Methods: PubMed was searched for studies reporting usage of AI/ML protocols for cancer diagnosis in prospective (clinical trial/real world) setting with the AI/ML diagnosis aiding clinical decision-making, from inception till May 17, 2021. Data pertaining to the cancer, patients and the AI/ML protocol were extracted. Comparison of AI/ML protocol diagnosis with human diagnosis was recorded. Through a post hoc analysis, data from studies describing validation of various AI/ML protocols were extracted. Results: Only 18/960 initial hits (1.88%) utilized AI/ML protocols for diagnostic decision-making. Most protocols used artificial neural network and deep learning. AI/ML protocols were utilized for cancer screening, pre-operative diagnosis and staging and intra-operative diagnosis of surgical specimens. The reference standard for 17/18 studies was histology. AI/ML protocols were used to diagnose cancers of the colorectum, skin, uterine cervix, oral cavity, ovaries, prostate, lungs and brain. AI/ML protocols were found to improve human diagnosis, and had either similar or better performance than the human diagnosis, especially made by the less experienced clinician. Validation of AI/ML protocols was described by 223 studies of which only four studies were from India. Also there was a huge variation in the number of items used for validation. Interpretation & conclusions: The findings of this review suggest that a meaningful translation from the validation of AI/ML protocols to their actual usage in cancer diagnosis is lacking. Development of regulatory framework specific for AI/ML usage in healthcare is essential. [ABSTRACT FROM AUTHOR]

BACKGROUND: Real-world safety of bevacizumab in cancer patients is limited. OBJECTIVE: To review the adverse drug reactions (ADRs) due to bevacizumab in cancer patients, in published case reports. METHODS: PubMed was searched; case reports of patients with any type of cancer, administered with bevacizumab (monotherapy/combination) and reported ADRs were included. Causality of ADRs was presented as reported in individual papers. ADRs were classified using the information in the USFDA-approved prescribing information (PI) of bevacizumab as 'Serious', 'Common', and 'Post-marketing surveillance' ADRs; ADRs not mentioned in the bevacizumab PI were termed as 'Non-label ADRs'. RESULTS: A total of 130 published papers comprising 154 cases from 22 different countries were included. Most papers (102/130; 78.46%) had moderate methodological quality. Age range of patients was 9-77 years. Off-label use of bevacizumab was found in 34/154 cases (22.08%). Ninety-six unique ADRs were found among 154 ADRs; most reported ADRs affected circulatory, digestive, and respiratory systems (33, 32, and 26 cases respectively). Most commonly reported ADRs were posterior leukoencephalopathy, fistulae, and gastrointestinal perforation (17, 17, and 16 cases respectively). Twenty-eight unique non-label ADRs (29.17%) were found. CONCLUSION: Bevacizumab is associated with more ADRs in the real world among cancer patients than those reported during clinical trials. [ABSTRACT FROM AUTHOR]

Introduction and Objective: Ivermectin (IVM) and doxycycline (DOXY) have demonstrated in-vitro activity against SARS-CoV-2, and have a reasonable safety profile. The objective of this systematic review was to explore the evidence in the literature on the safety and efficacy of their use as monotherapy and combination therapy in COVID-19 management.Methods: After prospectively registering the study protocol with the Open Science Framework, we searched PubMed, Google Scholar, clinicaltrials.gov, various pre-print servers and reference lists for relevant records published until 16 February, 2021 using appropriate search strategies. Baseline features and data pertaining to efficacy and safety outcomes were extracted separately for IVM monotherapy, DOXY monotherapy, and IVM + DOXY combination therapy. Methodological quality was assessed based on the study design.Results: Out of 200 articles screened, 19 studies (six retrospective cohort studies, seven randomised controlled trials, five non-randomised trials, one case series) with 8754 unique patients with multiple stages of COVID-19 were included; four were pre-prints and one was an unpublished clinicaltrials.gov document. The comparator was standard care and 'hydroxychloroquine + azithromycin' in seven and three studies respectively, and two studies were placebo controlled; six studies did not have a comparator. IVM monotherapy, DOXY monotherapy and IVM + DOXY were explored in eight, five and five studies, respectively; one study compared IVM monotherapy and IVM + DOXY with placebo. While all studies described efficacy, the safety profile was described in only six studies. Efficacy outcomes were mixed with some studies concluding in favour of the intervention and some studies displaying no significant benefit; barring one study that described 9/183 patients with erosive esophagitis and non-ulcer dyspepsia with IVM + DOXY (without causality assessment details), there were no new safety signals of concern with any of the three interventions considered. The quality of studies varied widely, with five studies having a 'good' methodological quality.Conclusions: Evidence is not sufficiently strong to either promote or refute the efficacy of IVM, DOXY, or their combination in COVID-19 management.Systematic Review Protocol Registration Details: Open Science Framework: https://osf.io/n7r2j . [ABSTRACT FROM AUTHOR]

To review the importance of evidence-based methods in health insurance reimbursement for achieving universal health coverage in India. A narrative literature review was performed. The out-of-pocket (OOP) healthcare expenditure in India is among the highest in the world. This situation is despite the implementation of numerous government health schemes and the availability of a large number of health insurance programs, both public and private. Compromised quality of care in many public healthcare facilities is a major factor driving the average Indian citizen to increasingly depend upon private healthcare facilities, further escalating OOP spending. The low awareness and poor uptake of insurance policies among Indians is one of the biggest challenges in the implementation of universal health coverage (UHC) in India. The catastrophic burden of high OOP expenses on individual households could be reduced by taking steps to enhance health insurance uptake, which can be in turn achieved by strengthening the healthcare reimbursement system in India. The application of the principles of evidence-based healthcare for reimbursement requires the systematic assessment of all health technologies, which is already being done in developed countries. The enactment of health schemes such as Ayushman Bharat-Pradhan Mantri Jan Arogya Yojana and setting up of Health Technology Assessment in India are steps toward reducing OOP expenditure and achieving UHC in India. We review the importance and challenges of evidence-based reimbursement and health technology assessment toward achieving UHC in India. • Indian households bear a high out-of-pocket expenditure on healthcare in India. • Introducing evidence-based reimbursement and health technology assessment would encourage the insurance uptake. • This would reduce the expenditure and improve the access to quality healthcare. • By launching the Ayushman Bharat public health insurance and assurance scheme, and by setting up Health Technology Assessment in India, the country is taking bold steps for providing universal health coverage to its citizens. [ABSTRACT FROM AUTHOR]

With healthcare becoming digital, patients today are more empowered than ever before. As a result, digital health solutions have become the need of the hour to keep up with an increasing number of empowered patients participating in their own treatment decisions. Digital health encompasses various platforms and systems that apply technological solutions to enhance healthcare delivery. Digital therapeutics (DTx) is one such category of digital health solutions that provides evidence-based software-driven therapeutic interventions for the prevention and management of a medical disorder or disease. This review aims to provide a comprehensive overview of DTx, its functions and applications in healthcare, and associated regulatory aspects, among others. [ABSTRACT FROM AUTHOR]

Most of the industrial sectors of India have undergone major changes in the post-liberalization period. During this period, India has become self-reliant in drugs; however, still, 75% of the medical devices are imported in India. According to WHO, almost all devices present in the developing countries have been designed for use in the industrialized countries. With the increase in incidence of non-communicable diseases and decrease in communicable diseases; increase in survival rates and decrease in mortality rates, and increase in ageing population, the healthcare demands have changed in the last decade. In addition to these parameters, aware patients and healthcare professionals, requirement of achieving national targets of healthcare and close proximity to the developed world, is giving a push to the development of indigenous medical device industry. However, the rules and regulations governing medical devices are ambiguous and vague. The Health Ministry of India has notified Medical Devices Rules, 2016, for regulating manufacturing/import/sale/clinical investigation and other related matters concerning medical devices. In addition, the government is funding the start-up industries in medical devices sector. Furthermore, government has taken the initiative of inverted duty structure in India. Also, special med tech zones are being set-up, which will enhance the production at local levels for the local population and will also generate employment for local people. [ABSTRACT FROM AUTHOR]

Background: In the process of drug development and drug approval, the pharmaceutical industry is challenged with increasing cost constraints, a growing need for real-world evidence and heavier regulatory scrutiny. Patient advocacy groups can be a valuable partner to the pharmaceutical industry in speeding up drug access. Patient advocates possess practical rather than purely scientific knowledge that is valuable for both drug development and drug approval. It was recognized quite early the patient advocacy groups and the pharmaceutical industry have similar goals. This understanding resulted in supporting patient involvement across the entire process of drug development, from discovery to USFDA approval for marketing. Support received by the patient advocacy groups include fundraising for research and development, organizing patients to expedite clinical trials, lobbying government and payer organizations to create public awareness, building support for research funding, and so on. Patient advocacy groups also back research for "orphan" diseases where there is a desperate need for new therapies. The recent success of Vertex and Sprout Pharmaceutical highlights the power of the patient voice in healthcare decision-making especially for orphan diseases. Conclusion: Working with patient groups can thus lead to a win-win situation for both the FDA and pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Randomized controlled trials (RCTs) are the gold standard for measuring the safety and efficacy of drugs. However, they are being challenged by payers and health care providers since they are looking for real world evidence (RWE) to validate whether the new intervention provides similar safety and efficacy as reported in RCT data. RWE uses real world data (RWD) to generate insight, foresight, and explorative findings on diseases, products, and patient populations. There are varied sources of RWD such as administrative data, large pragmatic trials, registries, electronic health records, and health surveys. RWE approaches are increasingly becoming the normal practice in developed countries to bring a product to the healthcare market and to ensure its significance in clinical practice. The Indian healthcare sector is growing at a brisk pace and is grasping up with the principles of health economics and outcome research, thereby exhibiting the value of real-world insights in healthcare decision. India has taken a step toward RWE by developing a framework to assist health care providers in harmonizing RWD for economic, clinical, and humanistic outcome. [ABSTRACT FROM AUTHOR]

One of the important components of patient-centered healthcare is comparative effectiveness research (CER), which aims at generating evidence from the real-life setting. The primary purpose of CER is to provide comparative information to the healthcare providers, patients, and policy makers about the standard of care available. This involves research on clinical questions unanswered by the explanatory trials during the regulatory approval process. Main methods of CER involve randomized controlled trials and observational methods. The limitations of these two methods have been overcome with the help of new statistical methods. After the evidence generation, it is equally important to communicate the results to all the interested organizations. CER is beginning to have its impact in the clinical practice as its results become part of the clinical practice guidelines. CER will have far-reaching scientific and financial impact. CER will make both the treating physician and the patient equally responsible for the treatment offered. [ABSTRACT FROM AUTHOR]

Background: World Health Organization (WHO) recommends the use of Xpert MTB/RIF assay for rapid diagnosis of tuberculosis (TB) and detection of rifampicin resistance. This systematic review was done to know about the diagnostic accuracy and cost-effectiveness of the Xpert MTB/RIF assay. Methods: A systematic literature search was conducted in following databases: Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, MEDLINE, PUBMED, Scopus, Science Direct and Google Scholar for relevant studies for studies published between 2010 and December 2014. Studies given in the systematic reviews were accessed separately and used for analysis. Selection of studies, data extraction and assessment of quality of included studies was performed independently by two reviewers. Studies evaluating the diagnostic accuracy of Xpert MTB/RIF assay among adult or predominantly adult patients (≥14 years), presumed to have pulmonary TB with or without HIV infection were included in the review. Also, studies that had assessed the diagnostic accuracy of Xpert MTB/RIF assay using sputum and other respiratory specimens were included. Results: The included studies had a low risk of any form of bias, showing that findings are of high scientific validity and credibility. Quantitative analysis of 37 included studies shows that Xpert MTB/RIF is an accurate diagnostic test for TB and detection of rifampicin resistance. Conclusion: Xpert MTB/RIF assay is a robust, sensitive and specific test for accurate diagnosis of tuberculosis as compared to conventional tests like culture and microscopic examination. [ABSTRACT FROM AUTHOR]

Introduction: Cancer is reported to cause about 0.4 million deaths annually. The cost of diagnosis and treatment of cancer in India is enormous. Aim: This Health Technology Assessment (HTA) aims to understand the role, effect on mortality and adverse event occurrence, and cost effectiveness of phytomedicine in cancer treatment. Materials and Methods: Health technology assessment by systematic review of published literature. An electronic literature search was performed in Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Medline, PubMed, Science Direct, SCOPUS, EMBASE, LANCET, and Google Scholar databases for randomized controlled trial, observational analytical studies, case control and cohort studies pertaining to phytomedicine and herbal medicine in cancer treatment published from 1987 till 2nd November 2014. Overall outcome measures collected included changes in mortality and adverse event profile. Cochrane Review Manager's Risk of Bias Table was used to assess the risk of bias. Results: Out of 76 studies which were screened, 14 studies involving a total of 1965 participants (817 received various forms of phytomedicine or herbal medicine in addition to conventional therapy, and 1148 received conventional therapy only) suffering from various cancers (including cancers of the breast, prostate, nasopharynx, pancreas, stomach, ovary, non-small cell lung cancer and osteosarcoma), were included in this review. In comparison with conventional therapy, phytomedicine resulted in a significant reduction in mortality: Risk Ratio (RR) 0.67 (95% Confidence Interval (CI) 0.51 to 0.90). The combination of phytomedicine with conventional therapy resulted in a significant reduction in adverse drug reactions: RR 0.62 (95% CI 0.54 to 0.71). Addition of phytomedicine to chemotherapy resulted in an increase in the annual cost of treatment by INR 1.241 Billion (US$ 19.64 Million) and prevented 25,217 deaths: the cost-effectiveness of phytomedicine is INR 49,237/death averted (US$ 779/death averted). Conclusion: When taken with conventional cancer treatment, phytomedicine shows clinical and cost effectiveness. Domestic manufacturing and practice of phytomedicine should be encouraged. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of canagliflozin in combination therapy among patients with type 2 diabetes mellitus with inadequate glycemic control. Methods: Two review authors independently searched for the relevant randomized controlled clinical trials from the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, IndMed, LILACS, and clinical trials registry www.clinicaltrials.gov. Primary outcomes for this review included: change in hemoglobin A1c (HbA1c) levels, fasting plasma glucose (FPG) levels and risk of occurrence of genital mycotic infections at 26 weeks. We combined results using mean difference (MD) for continuous data, and risk ratio (RR) for dichotomous data. Results: Of the 124 identified reports, five RCTs with 3565 participants were eligible for the meta-analysis. All included studies had compared canagliflozin 100 mg and 300 mg once daily with placebo or sitagliptin 100 mg once daily. We judged that most of the studies had low risk of bias or unclear risk of bias in five major domains. Canagliflozin 300 mg once daily led to a significant decrease in HbA1c levels (IV Fixed -0.77, 95% CI [-0.90, -0.64] P < 0.00001) and FPG levels (IV Fixed -2.08; 95% CI [-2.32, -1.84], P <0.00001), body weight, systolic blood pressure and triglyceride levels after 26 weeks as compared to placebo. There was a also a significant difference in the efficacy of canagliflozin 300 mg and sitagliptin 100 mg once daily in favour of canagliflozin. Both doses of canagliflozin led to genital mycotic infections among males and females, urinary tract infections, pollakiuria, polyuria and postural dizziness. Conclusions: Canagliflozin significantly decreases HbA1c and FPG levels and body weight as compared to placebo among patients with inadequate glycemic control with an earlier regime of glucose lowering agents. Long term safety studies are required to evaluate the incidence of adverse events. [ABSTRACT FROM AUTHOR]

In an attempt to reduce costs of clinical trials and increase recruitments, pharmaceutical companies have been shifting their trials to offshore locations in Asia, Africa, the Middle East, Eastern Europe, and Latin America. Hence, methods for conducting clinical trials need to be adapted to the varying languages, cultures, ethnicities, and socioeconomic groups of these regions. This is of prime importance in the collection of patient-reported outcome (PRO) data. To ensure correct capturing of PRO data from multiregional sites, it is important that the tools for data collection are adapted to the respective cultures, and the data collected have the same interpretation across cultures (cross-cultural equivalence). This article deals with challenges involved in the adaptation of PRO measures to various cultures, especially of those used for multiregional trials being conducted in the developing world. [ABSTRACT FROM AUTHOR]

Health Technology Assessments (HTAs) are gaining importance with support of governments in the Western World. With evidence synthesis and economic modeling gaining in accuracy and complexity, there is an increasing demand to assess the quality and validity of the data used for these studies. In keeping with the trend of the "Big Data" explosion, "Real World Evidence" is being seen as the answer to getting HTAs to the next level of accuracy. Hence there is the need for better tools to document and process "Real World Data". Registries have been existing for more than half a century now. However; their use was primarily done for epidemiological research. This article discusses how with the turn of the century, registries have evolved from being just portals for enrolment of patients to being highly sophisticated tools for economic modeling and cost analysis. We also discuss the challenges faced in optimal utilization of registries and how they can be addressed by better designing and implementation. We also discuss some policy decisions which have been taken to ensure that registries will continue to evolve and be a very important tool in HTAs. [ABSTRACT FROM AUTHOR]

Patients are the most valuable and authoritative source of information on outcomes like health-related quality of life, functional status, symptom and symptom burden and health behaviors. However, even traditionally, the only information collected from patients was feedback on satisfaction or experience with care. Patients have always remained an untapped resource in assessing the quality of healthcare and of long-term support services. The scenario has however changed with the increasing realization of Patient-Reported Outcome Measures (PROMs) as an efficient quality improvement tool. Routine collection of patient-reported outcomes (PROs) to inform, compare and manage healthcare professionals and facilities are implemented in a number of countries, including England, Australia, United States of America, Sweden, and the Netherlands. This review article discusses examples of PROMs in routine practice in some countries to illustrate the importance of building capacity and infrastructure to capture PRO routinely and utilize that data for developing performance measures for assessing provider's quality and efficiency. Also, discussed are the barriers to implementation of PROMs and factors responsible for its minimal influence on patient outcomes and ineffectiveness in comparing hospital performance. Finally lesson for health care policy makers especially Indian health care policy makers for successful implementation of PROMs are summarized. [ABSTRACT FROM AUTHOR]

Objectives: The present study was undertaken to provide the health professionals who were working at a tertiary care hospital, with a simple method to report Adverse Drug Reactions (ADRs) and to monitor, document and to evaluate them according to the set criteria. Method and Materials: This study was conducted over a period of 15 months from 1st Jan' 2008 to 31st March 2009 at Goa Medical College and Hospital (Goa, India). The evaluation of the data was done for various parameters, which included patient demographics and drug and reaction characteristics. An assessment was also done for the outcome, causality and the severity of the drug reactions. Results: A total of 265 ADRs were reported. Among the drugs, the β-lactam antibiotics were implicated the maximum number of times (54, 20.37%), followed by fluoroquinolones (35, 13.20%), antiretrovirals (33, 12.45%) and antiepileptics (31, 11.69%). Females showed more ADRs (142, 54%) than males (123, 46%). The skin was involved in about 57.73% (153) of the ADRs, while the CNS and the vascular system were involved in 8.67% (23) and 8.30% (22) of the ADRs. Most of the ADRs were categorized as "Type II" (203, 77%) against "Type I" (62, 23%) by Rawlins and Thompson's classification. The causality assessment was done by the Naranjo Algorithm and 62.26% (165) were seen to fall in the "probable category" as compared to 29.05% (77) in the "highly probable" one. Out of all the ADRs which were reported, 34.71% (148) were "severe", in accordance with the Modified Hartwig and Siegel's scale. Conclusion: The present work was a humble attempt to set up a well organized ADR reporting system at our government hospital. The systematic tracking and monitoring of ADRs can shed light on their extensiveness and their patterns of occurrence. [ABSTRACT FROM AUTHOR]

Although efficacy and safety data from randomized clinical trials (RCT) is considered to be the key to evidence generation, it is no longer adequate to meet all needs of Indian healthcare decision makers. Supplementing RCT data with robust observational studies data (OSD) as a decision making tool is being increasingly used by many payer advisors. Health Technology Assessment (HTA) agencies and healthcare bodies meaningfully use OSD for numerous purposes including, to confirm results of RCTs, justify utility estimates in economic models and demonstrate durability of effects of healthcare interventions. The phenomenal growth of Indian healthcare field has necessitated the need for robust HTA involving RCT data and OSD for better decision making. OSD may come a long way in supplementing Indian stakeholders in making rational healthcare decisions. It will be interesting to see how frequently OSD will be utilized in the Indian healthcare sector, and also how meaningfully, in the future. [ABSTRACT FROM AUTHOR]

With the Indian patient becoming more empowered with regards to his disease and its treatment options, many Indian physicians still depend only on disease-related outcome measures to take health-care related decisions, and give minimal importance to patient-centered outcomes pertaining to the effect of the healthcare interventions on the patient's well-being. Thus, objective lab values and physician intuition are given more importance than the subjective feeling of well-being that the patient is experiencing following the introduction of the intervention. This review presents a concept of integrating patient-centered and patient-reported data with the existing disease-centered and doctor-reported data for making healthcare-related decisions. This concept, termed patient-centered outcomes research, has already become popular in the Western World. [ABSTRACT FROM AUTHOR]

The article focuses on the role of medical advisor in providing quality medical care services to patients in pharmaceutical industries in India. Topics discussed include the development of pharmacovigilance (PVig) activities, drug promotions and conducted medical education programs. It also highlights the development of educational training systems for medical advisors to enhance its ability and knowledge towards drugs and drug development.