Collaborative Biomedical Research Research Articles

ScFed: federated learning for cell type classification with scRNA-seq.

The advent of single-cell RNA sequencing (scRNA-seq) has revolutionized our understanding of cellular heterogeneity and complexity in biological tissues. However, the nature of large, sparse scRNA-seq datasets and privacy regulations present challenges for efficient cell identification. Federated learning provides a solution, allowing efficient and private data use. Here, we introduce scFed, a unified federated learning framework that allows for benchmarking of four classification algorithms without violating data privacy, including single-cell-specific and general-purpose classifiers. We evaluated scFed using eight publicly available scRNA-seq datasets with diverse sizes, species and technologies, assessing its performance via intra-dataset and inter-dataset experimental setups. We find that scFed performs well on a variety of datasets with competitive accuracy to centralized models. Though Transformer-based model excels in centralized training, its performance slightly lags behind single-cell-specific model within the scFed framework, coupled with a notable time complexity concern. Our study not only helps select suitable cell identification methods but also highlights federated learning's potential for privacy-preserving, collaborative biomedical research.

Burden of Sexually Transmitted Infections (STI) in Rural and Peri-Urban KwaZulu-Natal, South Africa: Findings from a Population-Based Household Survey

Background: Sexually transmitted infections (STI) contribute to enhancing HIV transmission and acquisition; however, population level prevalence of STI from high HIV burden settings are limited Methods: A population-based household survey undertaken between June 2014 and June 2015 enrolled 15–49 year old males and females in the Vulindlela and Greater Edendale areas of KwaZulu-Natal, South Africa. Data collected includedself-reported sociodemographic, behavioral, and clinical variables. For curable STIs, first-pass urine (males) or self-collected vulvo-vaginal swabs (females) were tested for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Mycoplasma genitalium using multiplex real-time polymerase chain reaction (PCR) and for syphilis serum sample was tested using a non-treponemal rapid plasma reagin (RPR) assay. Herpes simplex virus type 2 (HSV-2) and HIV antibodies were assessed by enzyme-linked immunosorbent assays. Prevalence of all STIs was measured and the association between participant characteristics and curable STIs was estimated using Poisson regression. Findings: Among the 9812 enrolled participants, 38·9% were under the age of 25 years and 63·9% were females. Among males and females, the prevalence of HIV was 28·0% and 44·1%, p<0·001; HSV-2 was 46·1% and 68·8%, p<0·001. Overall, 15·5% of males and 27·8% of females tested positive for any curable STI; syphilis was 1·5% and 1·7%, p=0·62; N. gonorrhoeae 1·8% and 3·7%, p<0·001; C. trachomatis was 5·1% and 9·0%, p<0·001; T. vaginalis was 3·9% and 13·8%, p<0·001 and M. genitalium was 5·7% and 5·2%, p=0·43. Most STIs were higher in females and in HIV positive individuals. Infection with curable STIs in males was associated with age, drug use, and HIV positive status. In females, infection was associated with age, relationship status, number of lifetime partners, concurrent relationship, alcohol use, and HIV status. Viral suppression was associated with lower STI prevalence in both HIV positive males and females. Conclusions: The prevalence of curable STIs, HSV-2 and HIV was high in this population. These findings have important public health implications for HIV transmission and acquisition and justify the importance of population-based surveillance to monitor STIs in order to reduce STI related morbidity and mortality, improve the quality of sexual and reproductive health, and to reduce the STI and HIV syndemic. Funding Statement: Supported by the President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC) under the terms of operative agreement 3U2GGH000372-02W1. ABMK is supported by the joint South Africa–US Program for Collaborative Biomedical Research from the National Institutes of Health (R01HD083343). Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: The protocol, informed consent and data collection forms were reviewed and approved by the Biomedical Research Ethics Committee of the University of KwaZulu-Natal, (Reference number BF269/13), and the KwaZulu-Natal Provincial Department of Health (HRKM 08/14). The protocol was also reviewed in accordance with the Centers for Disease Control and Prevention (CDC), United States of America human research protection procedures and was determined to be research, but CDC investigators did not interact with human subjects or have access to identifiable data or specimens for research purposes.

Development and Deployment of an Open, Modular, Near-Real-Time Patient Monitor Datastream Conduit Toolkit to Enable Healthcare Multimodal Data Fusion in a Live Emergency Department Setting for Experimental Bedside Clinical Informatics Research

Healthcare providers rely on complex biomedical devices to assess, treat, and monitor patients. Ongoing research efforts are attempting to generate and implement better algorithms and mechanisms to ensure the early, accurate, automated, and clinically meaningful recognition of patterns and changes in patient health and pathology. Effecting such evolutionary advances in patient monitoring will likely require large collections of high-resolution physiologic parameter datasets from a broad spectrum of patients. As part of a research program to scientifically improve patient monitoring (with a focus on alarm fatigue mitigation), investigators developed the Medical Technology Interface-Open/Research toolkit with modular conduit components that provide the following capabilities: 1) access to select bedside monitor physiologic signals in real-world clinical settings for near-real-time acquisition, storage, and export of high-resolution patient datastreams in a portable format (.json); 2) establishment of a safe, parallel test environment at the bedside for experimental datastream analyses in a research framework. Deployment and interfacing of toolkit elements with off-the-shelf software solutions in a live emergency department setting enabled the construction of a bedside clinical informatics (BCI) research pipeline infrastructure that featured 1) indexing, search/query, and retrieval of datastreams for sophisticated analyses, experimental processing, and algorithm development; and 2) dataset visualization for expert adjudication of datastream interpretability, alarm clinical significance and severity, and experimental algorithm performance. In order to help institute a collaborative biomedical engineering research resource, this article shares details of the active ED BCI data pipeline and presents preliminary examples of ongoing multimodal data fusion applications.

Towards diaspora-driven research capacity strengthening in low- and middle-income countries: results from India and Nepal.

Biomedical research from high-income countries often informs practice and policy in low- and middle-income countries (LMICs) with vastly different socioeconomic and health systems. Engagement of LMIC-based researchers is integral to setting research priorities in the local context. A program, comprising a research seminar and workshop, and utilizing diaspora health professionals to understand research needs and build research capacity in LMICs, was created and pilot-tested at two institutions in India (65 participants) and Nepal (30 participants). Pre- and post-program surveys were instituted to assess participants' attitudes towards research. In the pre-program survey, most participants (India: 76%, Nepal: 100%) perceived research as 'very/extremely important' in their careers. However, a majority felt that finding time (India: 75%, Nepal: 81%) and funding (India: 82%, Nepal: 100%) for research was 'difficult/very difficult'. After the program, 86-91% and 86-100% of participants from India and Nepal, respectively, felt that the various courses were very useful/useful for their research careers. Research is seen as an integral part of educational training and career advancement in LMICs. However, inadequate training, funding and mentorship remain a challenge. Engagement of diaspora health workers may serve as an important avenue for collaborative biomedical research capacity strengthening in LMICs.

Appropriateness of no-fault compensation for research-related injuries from an African perspective: an appeal for action by African countries

Compensation for research-related injuries (RRIs) remains a challenge in the current environment of global collaborative biomedical research as exemplified by the continued reluctance of the US government, a major player...

Body Mass Index is a Strong Predictor of Low Serum 25(OH)D Levels in Multiethnic Obese Children in Western Massachusetts

The objective of the study is to examine the association between low serum 25(OH)D levels (VDL) and BMI category in children, adjusting for sex, ethnicity, age, CVD risk markers, season and nutrient intakes. 99 obese (BMI&gt; 95%) children aged 5–16 years participated in this cross sectional study conducted in a Pediatric Weight Management Clinic in Western Massachusetts. Nutrient intakes (Block Kids 2004 FFQ) and serum 25(OH)D were measured. Sunlight exposure, BMI, waist circumference (WC), BP, ethnicity, 25(OH)D, calcium, PTH, HbA1C, AST/ALT, fasting insulin, glucose, lipids and hsCRP data were obtained. Multivariable logistic regression was used to examine the relationship between VDL and BMI category, adjusting for potential confounders. Of 91 children completing the FFQ, mean 25(OH)D was 21.2 (±7.7) ng/mL and the mean BMI z‐score was 2.4 (±0.4). Using the Institute of Medicine (IOM) criteria, 25(OH)D was categorized into &lt;15ng/mL (22.0%) and normal (≥15 ng/mL; 78%)., and BMIz, into &gt;2.5 37.4%) and ≤ 2.5 (62.6%. Mean age 10.9±2.6 (SD) yrs, 22.0% African American, 26.4% Caucasian and 51.7% Hispanic, 52.8% female. Among those with BMI z‐scores less than 2.5, 15.8% had low 25(OH)D levels vs. 32.4% among those with BMI z‐scores at 2.5 or greater. That is, children with BMI z‐scores &gt; 2.5 have 2.55 greater odds of having a low 25(OH)D level compared to those with BMI z‐scores &lt;2.5 (OR=2.55, 95%CI: 0.93, 11.16; p=0.07). In logistic regression analysis, adjusting for gender, ethnicity, season, and age, children with BMI z‐scores &gt;2.5 had a significant 5.14 greater odds of low 25(OH)D compared to children with BMI z‐scores ≤2.5 (95%CI: 1.30, 20.36; p = 0.02). Additional adjustment for energy‐adjusted nutrient values, waist circumference, and selected cardiovascular risk factors did not change this relationship. Obese children are at risk for vitamin D deficiency. This risk increases in children with severe obesity (BMIz &gt; 2.5 SD) and is not significantly changed by season, ethnicity, nutrient intakes or sunlight exposure. More research is needed to further elucidate the mechanisms that influence vitamin D levels in this vulnerable population.Support or Funding InformationThis work was funded by UMASS‐Baystate Medical Center Collaborative Biomedical Research.

Organizational principles of cloud storage to support collaborative biomedical research.

This paper describes organizational guidelines and an anonymization protocol for the management of sensitive information in interdisciplinary, multi-institutional studies with multiple collaborators. This protocol is flexible, automated, and suitable for use in cloud-based projects as well as for publication of supplementary information in journal papers. A sample implementation of the anonymization protocol is illustrated for an ongoing study dealing with Automated Prediction of EXtubation readiness (APEX).

Life sciences domain analysis model

ObjectiveMeaningful exchange of information is a fundamental challenge in collaborative biomedical research. To help address this, the authors developed the Life Sciences Domain Analysis Model (LS DAM), an information model that provides a framework for communication among domain experts and technical teams developing information systems to support biomedical research. The LS DAM is harmonized with the Biomedical Research Integrated Domain Group (BRIDG) model of protocol-driven clinical research. Together, these models can facilitate data exchange for translational research.Materials and methodsThe content of the LS DAM was driven by analysis of life sciences and translational research scenarios and the concepts in the model are derived from existing information models, reference models and data exchange formats. The model is represented in the Unified Modeling Language and uses ISO 21090 data types.ResultsThe LS DAM v2.2.1 is comprised of 130 classes and covers several core areas including Experiment, Molecular Biology, Molecular Databases and Specimen. Nearly half of these classes originate from the BRIDG model, emphasizing the semantic harmonization between these models. Validation of the LS DAM against independently derived information models, research scenarios and reference databases supports its general applicability to represent life sciences research.DiscussionThe LS DAM provides unambiguous definitions for concepts required to describe life sciences research. The processes established to achieve consensus among domain experts will be applied in future iterations and may be broadly applicable to other standardization efforts.ConclusionsThe LS DAM provides common semantics for life sciences research. Through harmonization with BRIDG, it promotes interoperability in translational science.

A Japanese case of breast cancer with BRCA1 mutation

s / The Breast 20 (2011) S12–S55 S27 burden, and slower transfer of new discoveries and technologies into clinical practice. Methods: The objective of INTEGRATE, a European Commission funded project involving six European partners, is to build a data-sharing platform for all forms of data generated from clinical trials. The dynamic environment will collect, manage and provide secure and compliant access to complex and novel datasets for the biomedical community, including basic scientists, translational, and clinical researchers as well as the pharmaceutical industry to enhance cooperative research. It will be specifically designed to manage complex genomic data that can be used for molecular screening of patients for clinical trials as well as for analysis of clinical, pathology and imaging data. INTEGRATE will involve reuse and adaptation of existing openly available services and tools, as well as development of new technologies and analysis tools specifically for this data sharing environment. The INTEGRATE platform will initially be tested using data generated in neoadjuvant breast cancer clinical trials run by the Breast International Group (BIG). This will subsequently be expanded to include the setting of adjuvant and metastatic breast cancer and potentially other forms of cancer as well. Results: Experts from multiple disciplines, such as medical oncology, knowledge engineering, IT, basic bioscience, and ethical bodies have collaborated to define the scope of the platform. To ensure semantic interoperability and support reuse, the semantics of the domain will be captured in a core dataset using standardised terminologies such as SNOMED CT, ICD-O and LOINC, defined in collaboration with the end-user research community. The INTEGRATE platform will also support the development, preservation and sharing of multi-scale predictive models. The technical INTEGRATE environment will be based on an open serviceoriented architecture. An effort will be made to ensure that INTEGRATE is compatible with other similar existing platforms, and that the highest standards of data security and privacy are adopted. Conclusions: INTEGRATE will develop a standards-based environment that will support co-ordinated and collaborative biomedical research by allowing optimal exploitation of breast cancer clinical trial data, and thus potentially contribute to significant advancements in cancer research.

Working with Concepts: The Role of Community in International Collaborative Biomedical Research.

The importance of communities in strengthening the ethics of international collaborative research is increasingly highlighted, but there has been much debate about the meaning of the term ‘community’ and its specific normative contribution. We argue that ‘community’ is a contingent concept that plays an important normative role in research through the existence of morally significant interplay between notions of community and individuality. We draw on experience of community engagement in rural Kenya to illustrate two aspects of this interplay: (i) that taking individual informed consent seriously involves understanding and addressing the influence of communities in which individuals’ lives are embedded; (ii) that individual participation can generate risks and benefits for communities as part of the wider implications of research. We further argue that the contingent nature of a community means that defining boundaries is generally a normative process itself, with ethical implications. Community engagement supports the enactment of normative roles; building mutual understanding and trust between researchers and community members have been important goals in Kilifi, requiring a broad range of approaches. Ethical dilemmas are continuously generated as part of these engagement activities, including the risks of perverse outcomes related to existing social relations in communities and conditions of ‘half knowing’ intrinsic to processes of developing new understandings.

Building a biomedical research program in Qatar

The State of Qatar under the leadership of His Highness the Emir Hamad Bin Khalifa Al Thani has invested heavily into higher education and research infrastructure development through Qatar Foundation under the leadership of Her Highness Sheikha Mozah Bint Nasser Al Missned. Part of that effort is the establishment of the biomedical research program at Weill Cornell Medical College in Qatar (WCMC-Q), which, in collaboration with other stakeholders in Qatar, aims at instituting a world-class biomedical research program in Qatar. This presentation will highlight the efforts over the past two years expanded toward establishing the WCMC-Q research program. It will present a model for research infrastructure ramp-up in Qatar and the region. We will discuss: research support services including compliance and grants and contracts; the organization, staffing and high-end equipment of core research laboratories that are becoming increasingly important for collaborative biomedical research; and scientific areas of focus for the WCMC-Q program in the context of national priorities, including the diabetes, obesity and metabolic syndrome center of excellence that is underway.

Technology's role in healthcare reform

Technology's role in healthcare reform

Legal and ethical consequences of international biobanking from a national perspective: the German BMB-EUCoop project

The international transfer of human biomaterial and data has become a prerequisite for collaborative biomedical research to be successful. However, although a national legal framework for 'biobanking' has already been formulated in many countries, little is known about how an international exchange of data and samples might affect the legal position of national biobanks and their donors. The German Telematics Platform and the Competence Network 'Congenital Heart Defects' jointly instigated a project (BMB-EUCoop) to (i) identify and assess the legal risks ensuing for biobanks and their donors in the context of Europe-wide research collaborations, (ii) devise practical recommendations to minimize or avoid these risks, and (iii) provide generic informational text, contracts and agreements to facilitate their practical implementation. Four different countries were included in the study; namely, the UK, Netherlands, Austria and Switzerland. The results of the study indicate that the degree of similarity between legal systems in different countries varies according to the respective field of jurisdiction. Although personality and property rights have long been enshrined in virtually identical pieces of law, the applicable medical professional regulations were found to be somewhat heterogeneous. Furthermore, clear-cut differences were often found to be lacking between regulations that reflect either 'soft law' or the nationally binding 'hard law' that has emerged from it. In view of the potential ambiguities, the experts uniformly concluded that the rights and interests of national (in this case, German) biobanks and their donors would be best protected by explicitly addressing any uncertainties in formal contractual agreements.

The Heart-Brain Connection Begets Cardiovascular Psychiatry and Neurology

In many Asian languages, the same ancient letter/symbol is used for heart and mind. For the last couple of millennia, physicians and scientists across different civilizations have posited close links between the brain and heart, even arguing that the site of intelligence and emotions is in one of these two organs. Through an integrative empirical approach in modern biology/physiology and behavioral sciences, much has since been learned to confirm the anatomical and functional links between the brain and the heart. Arguably, the ultimate applicability of this knowledge will advance our health and improve disease treatment. Modern medicine is characterized by a high degree of specialization, and the heart-brain connection is typically considered from the point of view of a particular medical specialty. Hence, focusing on the brain, for example, in neurology, cardiovascular involvement is critical in certain pathologies such as stroke and vascular dementia. In cardiology, on the other hand, the influence of the brain becomes clearly apparent in “the broken heart syndrome” (also known as acute stress cardiomyopathy). However, recent epidemiological studies point to new associations that typically present as co-occurring pathologies of both the brain and the heart. A case in point is the association between depression and coronary heart disease. Such co-occurrences have stimulated research into possible novel mechanisms that could be targeted to treat these complex cardiovascular/brain disorders. At least three scenarios could be at play in these illnesses: (i) the primary pathological mechanism in the nervous system triggers a cardiovascular pathology by disrupting physiological links between the two systems (hence, the term “psychogenic”cardiovascular disease), (ii) the primary pathological mechanism in the cardiovascular system triggers a nervous system dysfunction (e.g., atherosclerosis leading to ischemic conditions causes subsequent cognitive impairment), and (iii) the primary pathology is in a biological mechanism that is normally operative in both the nervous and the cardiovascular systems, thus causing the co-occurrence of pathologies (i.e., the co-occurring pathologies share a pathobiological mechanism but do not necessarily cause each other). To be successful, research in co-occurring cardiovascular and brain disorders needs contributions from multiple medical specialties, including psychiatry, neurology, medicine, and cardiology. It should encompass clinical and basic research as well as the development of therapeutic approaches. The purpose of Cardiovascular Psychiatry and Neurology is to provide a platform for the latest research and for timely and expert reviews and comments in the emerging field of cardiovascular psychiatry and neurology. Although the term cardiovascular psychiatry and neurology is introduced here for the first time, retrieving publications from PubMed using either cardiovascular psychiatry or cardiovascular neurology generates relevant information (oftentimes because the terms psychiatry or neurology appear in the tile of a journal publishing the work). A quick survey of PubMed for the publication period from 1940 to 2008 (Table 1) revealed, not surprisingly, that the number of items per search term has increased dramatically over the years. Whereas the term cardiovascular showed a sharp increase in the early sixties, both neurology and psychiatry “exploded” in the early nineties. Even though the term cardiovascular psychiatry appeared earlier than cardiovascular neurology, the later term has become more prevalent since the early sixties (Table 1). Normalizing the data, that is, by expressing cardiovascular psychiatry as a percentage of corresponding psychiatry and cardiovascular neurology as a percentage of the corresponding neurology (Figure 1), showed that cardiovascular neurology rose sharply in the early sixties and has remained at about 5% of all neurology-related items. On the other hand, cardiovascular psychiatry had been below 1% of all psychiatry-related items until the early eighties, but has gradually increased. Possibly, the ischemia-related brain disorders have contributed to the relatively high presence of cardiovascular neurology and the relatively recent revelation of an unsuspected association of cardiovascular disorders with mood disorders might have contributed to the increase in cardiovascular psychiatry. The journal Cardiovascular Psychiatry and Neurology was created to provide for the first time a unified forum to consider the physiological and pathological interactions between the nervous and the cardiovascular systems. The journal aims to stimulate the development of relevant interdisciplinary and collaborative biomedical research and to foster multidisciplinary efforts in advancing medical practices. Figure 1 The proportions of retrieved PubMed terms Cardiovascular Psychiatry versus Psychiatry and Cardiovascular Neurology versus Neurology. The PubMed search was performed as described in Table 1. The percentages of items found for Cardiovascular Psychiatry ... Table 1 A number of PubMed items retrieved on January 13, 2009. The terms indicated in the table were searched (http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed) for the indicated publication dates (years). No systematic checking was performed for the actual ... Hari Manev

Chemical biology at the Broad Institute

The Broad Institute was founded with the vision of creating a truly collaborative biomedical research environment, and small molecules are a central focus.

A Collaborative Biomedical Research System

The convergence of need between improved clinical care and post genomics research presents a unique challenge to restructuring information flow so that it benefits both without compromising patient safety or confidentiality. The CLEF project aims to link-up heath care with bioinformatics to build a collaborative research platform that enables a more effective biomedical research. In that, it addresses various barriers and issues, including privacy both by policy and by technical means, towards establishing its eventual system. It makes extensive use of language technology for information extraction and presentation, and its shared repository is based around coherent chronicles of patients' histories that go beyond traditional health record structure. It makes use of a collaborative research workbench that encompasses several technologies and uses many tools providing a rich platform for clinical researcher.

A system for medical consultation and education using multimodal human/machine communication.

Recent developments in networking and computing have enabled collaborative biomedical engineering research by geographically separated participants. One of the most promising goals is to use these technologies to extend human intellectual capabilities in medical decision making. These emerging technologies are poised to drastically reduce healthcare cost by providing service at remote locations. This also increases diagnosis capacity since information is made available to experts at any location. In this paper, we propose a novel application of a recently developed interactive and distributed system in medical consultation and education. Our approach builds on the notion that interactive and distributive capabilities of the system are crucial for medical consultation and education. The presented application uses a multiuser, collaborative environment with multimodal human/machine communication in the dimensions of sight, sound, and touch. The experimental setup, consisting of two user stations, and the multimodal interfaces, including sight (eye-tracking), sound (automatic speech), and touch (microbeam pen), were tested and evaluated. The system uses a collaborative workspace as a common visualization space. Users communicate with the application through a fusion agent by eye-tracking, speech, and microbeam pen. The audio/video teleconferencing is also included to help the radiologists to communicate with each other simultaneously while they are working on the mammograms. The system used in this study has three software agents: a fusion agent, a conversational agent, and an analytic agent. The fusion agent interprets multimodal commands by integrating the multimodal inputs. The conversational agent answers the user's questions and detects human-related or semantic errors and notifies the user about the results of the image analysis. The analytic agent enhances the digitized images using the wavelet denoising algorithm if requested by the user. To show how well the system performs in practice, we used the system for medical consultation on mammograms. Results also show that the relevant information about the region of interest (ROI) of the mammograms chosen by the users is extracted automatically and used to enhance the mammograms.

Applied Collaborative Biomedical Anthropology in a State Health Department Setting

State health departments offer a diversity of collaborative research opportunities for biological anthropologists. This article discusses some of the issues one may confront in conducting collaborative biomedical research in this kind of setting, drawing on my experiences in the New York State Department of Health. Unlike an academic setting, the choice of a research topic is likely to depend upon the bureau in which one works and not solely on one's interests or prior specialty in biological anthropology. Though findings may not be publishable in anthropological journals, one can contribute to the literature of other disciplines. It is relatively easy to find collaborators from other disciplines, both inside and outside the health department, and collaboration has significantly broadened my knowledge.

COMPLEXITIES OF MEDICAL RESEARCH IN DEVELOPING COUNTRIES: STANDARD OF CARE: RESPONSIBILITIES OF ETHICS COMMITTEES

Increased awareness of human rights particularly those of vulnerable and emphasis on protection of less strong from stronger groups, have extended the limits of biomedical ethics where human participants are involved in the research. Inequalities amongst various global groups and subgroups in respect to financial resources and healthcare with increased collaborative biomedical research, particularly for-profit institutions have raised ethical issues one being the standard of care in research in developing countries. Emergence of newer and complex infectious diseases and resurgence of older ones in recent past has prompted Western world to undertake research in the Eastern hemisphere of the globe. But it has generated complex and various ethical dilemmas. Ethics demands that enrollees of research in developing countries not only be judiciously remunerated but outcomes of the studies be directly beneficial and affordable to them along with provision of parallel benefits. The core point of discussion amongst various partners is the selection from possible choices of standard of care to human participants in less developed countries. While some authors have argued for alternate standards whereas others suggest to compromise on this demand in particular conditions with permission from Ethics Committees. These suggestions, besides empowering the ERCs have put more burden on them to prepare guidelines and resolve the encountered issues where presently available guidelines are inadequate or insufficient. This work provides in-depth discussion and analyses possible alternatives to this complex dilemma.