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What would happen if on one day more than 50 people died and over 10 times that many were harmed by an infectious disease in the United States? Likely, our nation’s esteemed and highly capable public health infrastructure would gear up to care for those harmed and study the problem. There would be a rush to identify the cause, develop interventions, and refine them continually until the threat is eliminated or at least contained. In light of the risks to public health (after all, over 500 people have been harmed already!), health care professionals would sound the alarm. We would . . .

The International Committee of Medical Journal Editors (ICMJE) believes there is an ethical obligation to responsibly share data generated by interventional clinical trials because trial participants have put themselves at risk. In January 2016 we published a proposal aimed at helping to create an environment in which the sharing of deidentified individual participant data becomes the norm. In response to our request for feedback we received many comments from individuals and groups. (1) Some applauded the proposals while others expressed disappointment they did not more quickly create a commitment to data sharing. Many raised valid concerns regarding the feasibility of the proposed requirements, the necessary resources, the real or perceived risks to trial participants, and the need to protect the interests of patients and researchers. It is encouraging that data sharing is already occurring in some settings. Over the past year, however, we have learned that the challenges are substantial and the requisite mechanisms are not in place to mandate universal data sharing at this time. Although many issues must be addressed for data sharing to become the norm, we remain committed to this goal. Therefore, ICMJE will require the following as conditions of consideration for publication of a clinical trial report in our member journals: i) As of July 1, 2018 manuscripts submitted to ICMJE journals that report the results of clinical trials must contain a data sharing statement as described below. ii) Clinical trials that begin enrolling participants on or after January 1, 2019 must include a data sharing plan in the trials registration. The ICMJE's policy regarding trial registration is explained at www.icmje.org/recommendations/browse/ publishing-and-editorial-issues/clinical-trial-registration.html. If the data sharing plan changes after registration this should be reflected in the statement submitted and published with the manuscript, and updated in the registry record. Data sharing statements must indicate the following: whether individual deidentified participant data (including data dictionaries) will be shared; what data in particular will be shared; whether additional, related documents will be available (e.g. study protocol, statistical analysis plan, etc.); when the data will become available and for how long; by what access criteria data will be shared (including with whom, for what types of analyses and by what mechanism). Illustrative examples of data sharing statements that would meet these requirements are in the Table 1. These initial requirements do not yet mandate data sharing, but investigators should be aware that editors may take into consideration data sharing statements when making editorial decisions. These minimum requirements are intended to move the research enterprise closer to fulfilling our ethical obligation to participants. Some ICMJE member journals already maintain, or may choose to adopt, more stringent requirements for data sharing. Sharing clinical trial data is one step in the process articulated by the World Health Organization (WHO) and other professional organizations as best practice for clinical trials: universal prospective registration; public disclosure of results from all clinical trials (including through journal publication); and data sharing. Although universal compliance with the requirement to prospectively register clinical trials has not yet been achieved and requires continued emphasis, we must work towards fulfilling the other steps of best practice as well-including data sharing. As we move forward into this new norm where data are shared, greater understanding and collaboration among funders, ethics committees, journals, trialists, data analysts, participants, and others will be required. We are currently working with members of the research community to facilitate practical solutions to enable data sharing. …

A requirement of the International Committee of Medical Journal Editors

The International Committee of Medical Journal Editors (ICMJE) believes that there is an ethical obligation to responsibly share data generated by interventional clinical trials because participants have put themselves at risk. In a growing consensus, many funders around the world—foundations, government agencies, and industry—now mandate data sharing. Here we outline ICMJE’s proposed requirements to help meet this obligation. We encourage feedback on the proposed requirements. Anyone can provide feedback at www.icmje.org by 18 April 2016. The ICMJE defines a clinical trial as any research project that prospectively assigns people or a group of people to an intervention, with or without concurrent comparison or control groups, to study the cause-and-effect relationship between a health-related intervention and a health outcome. Further details may be found in the Recommendations for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals at www.icmje.org As a condition of consideration for publication of a clinical trial report in our member journals, the ICMJE proposes to require authors to share with others the deidentified individual-patient data (IPD) underlying the results presented in the article (including tables, figures, and appendices or supplementary material) no later than 6 months after publication. The data underlying the results are defined as the IPD required to reproduce the article’s findings, including necessary metadata. This requirement will go into effect for clinical trials that begin to enroll participants beginning 1 year after the ICMJE adopts its data-sharing requirements.* Enabling responsible data sharing is a major endeavor that will affect the fabric of how clinical trials are planned and conducted and how their data are used. By changing the requirements of the manuscripts we will consider for publication in our journals, editors can help foster this endeavor. As editors, our direct influence is logically, and practically, limited to those data underpinning the results and analyses we publish in our journals. The ICMJE also proposes to require that authors include a plan for data sharing as a component of clinical trial registration. This plan must include where the researchers will house the data and, if not in a public repository, the mechanism by which they will provide others access to the data, as well as other data-sharing plan elements outlined in the 2015 Institute of Medicine Report (e.g., whether data will be freely available to anyone upon request or only after application to and approval by a learned intermediary, whether a data use agreement will be required) (1). ClinicalTrials.gov has added an element to its registration platform to collect data-sharing plans. We encourage other trial registries to similarly incorporate mechanisms for the registration of data-sharing plans. Trialists who want to publish in ICMJE member journals (or nonmember journals that choose to follow these recommendations) should choose a registry that includes a data-sharing plan element as a specified registry item or allows for its entry as a free-text statement in a miscellaneous registry field. As a condition of consideration for publication in our member journals, authors will be required to include a description of the data-sharing plan in the submitted manuscript. Authors may choose to share the deidentified IPD underlying the results presented in the article under less restrictive, but not more restrictive, conditions than were indicated in the registered data-sharing plan. ICMJE already requires the prospective registration of all clinical trials prior to enrollment of the first participant. This requirement aims, in part, to prevent selective publication and selective reporting of research outcomes, and to prevent unnecessary duplication of research effort. Including a commitment to a data-sharing plan is a logical addition to trial registration that will further each of these goals. Prospective trial registration currently includes documenting the planned primary and major secondary end points to be assessed, which enables identification of incomplete reporting as well as post hoc analyses. Declaring the plan for sharing data prior to their collection will further enhance transparency in the conduct and reporting of clinical trials by exposing when data availability following trial completion differs from prior commitments. Sharing clinical trial data, including deidentified IPD, requires planning to ensure appropriate ethics committee or institutional review board approval and the informed consent of study participants. Accordingly, we will defer these requirements for 1 year to allow investigators, trial sponsors, and regulatory bodies time to plan for their implementation. Just as the confidentiality of trial participants must be protected (through the deidentification of IPD), and the needs of those reasonably requesting data met (through the provision of useable data), the reasonable rights of investigators and trial sponsors must also be protected. ICMJE proposes the following to safeguard these rights. First, ICMJE editors will not consider the deposition of data in a registry to constitute prior publication. Second, authors of secondary analyses using these shared data must attest that their use was in accordance with the terms (if any) agreed to upon their receipt. Third, they must reference the source of the data using a unique identifier of a clinical trial’s data set to provide appropriate credit to those who generated it and allow searching for the studies it has supported. Fourth, authors of secondary analyses must explain completely how theirs differ from previous analyses. In addition, those who generate and then share clinical trial data sets deserve substantial credit for their efforts. Those using data collected by others should seek collaboration with those who collected the data. However, because collaboration will not always be possible, practical, or desired, an alternative means of providing appropriate credit needs to be developed and recognized in the academic community. We welcome ideas about how to provide such credit. Data sharing is a shared responsibility. Editors of individual journals can help foster data sharing by changing the requirements of the manuscripts they will consider for publication in their journals. Funders and sponsors of clinical trials are in a position to support and ensure adherence to IPD sharing obligations. If journal editors become aware that IPD sharing obligations are not being met, they may choose to request additional information; to publish an expression of concern; to notify the sponsors, funders, or institutions; or in certain cases, to retract the publication. In the rare situation in which compliance with these requirements is impossible, editors may consider authors’ requests for exceptions. If an exception is made, the reason(s) must be explained in the publication. Sharing data will increase confidence and trust in the conclusions drawn from clinical trials. It will enable the independent confirmation of results, an essential tenet of the scientific process. It will foster the development and testing of new hypotheses. Done well, sharing clinical trial data should also make progress more efficient by making the most of what may be learned from each trial and by avoiding unwarranted repetition. It will help to fulfill our moral obligation to study participants, and we believe it will benefit patients, investigators, sponsors, and society.

A year ago, the editors of PLOS Neglected Tropical Diseases and PLOS Medicine launched the PLOS Blue Marble Health Collection, subtitled “the mismatch between national wealth and population health” [1]. The term “blue marble health” (which recalls the appearance of the earth from space) was coined as a differentiator from prior conceptualizations of global health that divided the world’s population according to national economic indices [2]. The basic tenet of blue marble health is that impoverished populations living amidst wealth bear a disproportionate burden of neglected diseases, irrespective of the overall economic strength of their home country. Such an approach is increasingly relevant as differential disease burdens between wealthier countries and regions (including North America, Europe, and Japan) and lower-income countries (including many in Africa, Asia, and Central and South America), evolve through a pronounced, but uneven, economic rise across the planet that leaves pockets of intense poverty in its wake. The concept of blue marble health grew out of a paradoxical observation by one of us (PJH) that most of the world’s neglected tropical diseases (NTDs) are found in concentrated areas where poor people live in the wealthiest economies, especially the group of 20 (G20) countries together with Nigeria [2]. A follow-up study published this week in PLOS Neglected Tropical Diseases, based on newer data released by the World Health Organization (WHO) for the year 2013, finds that at least one-half or more of the world’s helminth infections and most of the dengue fever cases are also endemic to the G20 nations and Nigeria [3]. A recent analysis, based on data from WHO and the Joint United Nations Programme on HIV/AIDS (UNAIDS), indicates that lack of protection by national economic power extends beyond the NTDs to include the so-called “big three diseases”: HIV/AIDS, tuberculosis, and malaria; overall, roughly one-half of the prevalent cases of tuberculosis and malaria in 2013 were found in the G20 and Nigeria, as were almost one-half of the people living with HIV/AIDS [4]. The policy implications of blue marble health related to infections include emphasizing the G20’s role in mass treatment of their own indigenous populations for NTDs; prevention and appropriate screening for HIV, TB and malaria; and committing resources to conduct research and development (R&D) [5]. The need for such a policy is based partly on studies that point to disproportionately small contributions by the BRICS (i.e., Brazil, Russia, India, China, and South Africa) and other G20 countries towards supporting health R&D globally [6]. If diseases long associated with poor countries, such as NTDs and other infections, are increasing among poor people in richer countries, what about diseases associated with rich countries? Noncommunicable diseases (NCDs), including such rich-country scourges as coronary artery disease, have for some years been increasing as causes of illness and death in low- and middle-income countries [7]. According to WHO’s Global Status Report on NCDs 2014 for the year 2012, globally approximately 38 million people died from NCDs, from a total of 56 million people who died in that year. The WHO finds that four major disease groups—cancer, cardiovascular diseases, chronic respiratory diseases, and diabetes—are responsible for 82% of the NCD-related deaths. Among them, cardiovascular diseases accounted for almost one-half of the deaths (17.5 million), followed by cancers (8.2 million), respiratory diseases such as asthma and chronic obstructive pulmonary disease (4.0 million), and diabetes (1.5 million) [8]. Are increases in NCDs limited to growing higher-income classes? In 2013, the G20 nations and Nigeria accounted for almost 90% of the global economy, as estimated by total global gross domestic product (GDP). While these nations represent the world’s economic engine, the G20 nations and Nigeria also produce most of the world’s neglected infectious diseases (including NTDs) and most of its NCDs. Shown in Table 1 is the NCD mortality for the G20 countries and Nigeria, indicating that the world’s wealthiest economies account for approximately 26.5 million deaths from NCDs, or 70% of the world’s NCD-related deaths. The age-standardized death rates clearly indicate that, among the world’s leading economic powers, a nation’s GDP by itself is a poor indicator of its inhabitants’ risk of dying from NCDs. Table 1 NCD mortality estimates in G20 countries + Nigeria, 20121. These WHO data do not distinguish between wealthy and poor populations within the G20 nations and Nigeria. However, previous work indicates that at least some NCDs have been associated with lower, rather than higher, socioeconomic status within LMICs [9]. Moreover, NCDs are on the decline in high-income countries but rising among LMICs, where most of the world’s NCD-related deaths (especially premature deaths) now occur [8]. Taken together with these findings, the wide range of NCD mortality rates among G20 countries, with particularly high rates among non-high-income G20 countries, seems consistent with a hypothesis that the poor living among the wealthy disproportionately share the burden of NCDs globally. In other words, NCDs may be joining NTDs, HIV, TB, and malaria in following the familiar blue marble health pattern of geographical redistribution with convergence on the world’s poorest people. These observations indicate the relevance of a blue marble health perspective in reshaping global health policy to include a spotlight on the G20 nations and Nigeria and targeting HIV/AIDS, tuberculosis, malaria, NTDs, and NCDs at future G20 summits. A specific component may include renewed commitments by these specific nations for access to health care and essential medicines for their own impoverished populations as well as those of lower-income countries. To this end, G20 nations should support the nine major targets that WHO has set to reduce global deaths from NCDs, with an overarching goal to reduce NCD deaths by one-quarter [8]. Important components include dietary and lifestyle changes, as well as access to essential medicines to control high blood sugar, high blood pressure, and other risk factors for cardiovascular diseases. In addition, there are a wide range of neglected causes of NCDs that are unique to people who live in extreme poverty [10] Ultimately, the world economic powers should also support R&D to address their own health disparities [11]. Recently, a global biomedical R&D fund has been proposed [5], which may be especially relevant to the G20 nations and Nigeria not only as supporters of improving health in less wealthy countries, but also as potential recipients of advances that will benefit the health of their own populations. Such measures must not be enacted while failing to address poverty and other social determinants underlying the patterns that blue marble health aims to improve. As Michael Marmot and others have noted, “Social determinants are relevant to communicable and non-communicable disease alike. Health status, therefore, should be of concern to policy makers in every sector, not solely those involved in health policy” [12]. In parallel, global efforts should ensure that implementation of public health measures does not inadvertently widen health inequalities, as recently found for some cardiovascular disease prevention measures [13]. Strong economies must take responsibility for population-wide preventive action that embraces vulnerable populations now living in extreme poverty. For research addressing the disparate burden of disease upon poor people across a variety of settings, PLOS Medicine and PLOS Neglected Tropical Diseases continue to encourage submissions to the recently updated Blue Marble Health Collection [1,14].

The PLoS Medicine Editors discuss how collisions between science and politics slow progress in public health.

The records of the San Francisco General Hospital (SFGH) Blood Bank were reviewed, and 263 likely AIDS and AIDS-related complex (ARC) patients were identified, who received 1545 units of packed red cells (PBRCs) between July 1, 1987, and June 30, 1988. A probability sample of 80 of these patients was selected randomly for detailed chart review. Of this sample, 78 (98%) were confirmed to have AIDS (86%) or ARC (14%). On the basis of the yearly census of the SFGH AIDS clinic, a transfusion incidence of 0.89 PRBC units per patient per year for patients with AIDS and 0.27 PRBC units per patient per year for those with ARC was estimated. Whereas 26 percent of the 177 transfusions studied in detail involved more than one associated (possibly causative) factor, antimicrobial drug therapy, zidovudine therapy, and disseminated Mycobacterium avium complex (MAC) infection were the sole associated factors in 20, 14, and 12 percent of the transfusions, respectively. To assess the role of MAC, the 263 transfused patients were compared with the 574 patients whose blood was submitted to the SFGH Mycobacteriology Laboratory during the same period. Patients whose blood yielded MAC had a relative risk of 5.2 for transfusion-requiring anemia. In 80 percent of cases, the patient returned home after transfusion. Most PRBC transfusions administered to AIDS or ARC patients were optimal therapy.

In May 2014, PLOS Medicine joined PLOS Neglected Tropical Diseases in launching the Blue Marble Health Collection [1], to which we now invite ongoing manuscript submissions. The collection (available at http://www.ploscollections.org/bluemarblehealth/) emerged from themes shared by both journals, and discussed in Editorials during 2013. First, a Viewpoint in PLOS Neglected Tropical Diseases [2] found that while some neglected tropical diseases (NTDs) such as river blindness, loiasis, African sleeping sickness, and schistosomiasis are largely or exclusively diseases of sub-Saharan Africa, paradoxically, many of the world's highest concentration of NTDs occur in the 20 wealthiest economies—the group of 20 (G20) countries—especially in the mostly hidden pockets of extreme poverty that can be found in the big middle-income nations, such as Indonesia, or in areas of the BRIC countries (Brazil, Russia, India, and China), including northeastern Brazil, northern India, and southwestern China. Moreover, the disease burden from NTDs is alarmingly high in the southern United States (especially in Texas and the Gulf Coast), in areas of Australia with large Aboriginal populations such as the Northern Territory, and in Eastern Europe. A parallel Editorial in PLOS Medicine [3] noted that relative poverty within a society is a stronger predictor of health than aggregate measures of economic power such as gross national product or per capita income. For example, tens of millions of Americans living in poverty, including many people of color, “experience levels of health that are typical of middle-income or low-income countries.” The Editorial concluded that, for many issues that affect the health of people of lower socioeconomic status, clear-cut distinctions between “domestic” and “cross-border” research are becoming increasingly difficult to draw. Blue Marble Health highlights a shift in current thinking about global health. Increasingly, an approach that emphasizes stark contrasts between “developing” and “developed” countries may no longer reflect reality. Instead, major health disparities—including NTDs, but possibly also other infections such as tuberculosis, as well as noncommunicable diseases—disproportionately affect poor people living among wealthier people. Having evolved from paradigms of international health (in which high-income countries assist lower-income countries) through global health (in which countries work together to address health issues that affect the global community), Blue Marble Health reflects the insight that wherever socioeconomic inequality is pervasive, neglected diseases and other conditions naively assumed to arise only in the context of national poverty will spread. To address these problems, Blue Marble Health calls for attention to socioeconomic as well as biomedical factors—whether in Nigeria, South Africa, Brazil, and India, or in the US, Europe, and Australia. At its launch in May 2014, the collection included more than 20 Editorials, Viewpoints, Policy Forums, and Research Articles from PLOS Neglected Tropical Diseases and PLOS Medicine, as well as an Essay from PLOS Biology. Each highlights a health disparity that disproportionately strikes poor people living in G20 countries or other countries generally thought of as well-off. The launching of the collection also coincided with the publication of a new PLOS Neglected Tropical Diseases Editorial that identifies ten global “hotspots” for endemic and epidemic NTDs [4]. Mahatma Gandhi once stated: “It is a trite saying that one half of the world knows not how the other lives. Who can say what sores might be healed, what hurts solved, were the doings of each half of the world's inhabitants understood and appreciated by the other?” [5] A century later, although the importance of mutual appreciation among diverse populations has only increased, the world no longer divides itself easily into halves on the basis of national boundaries or economic cut-points. Amartya Sen, who was awarded the Sveriges Riksbank Prize in Economic Sciences in 1998, has articulated a distinction between “the difficult problem of assessing the richness of human lives, including the freedoms that human beings have reason to value, and…the much easier exercise of keeping track of incomes and other external resources that persons—or nations—happen to have” [6]. In Sen's words, “human well-being and freedom, and their connection with fairness and justice in the world, cannot be reduced simply to the measurement of GDP and its growth rate, as many people are tempted to do.” The term “Blue Marble Health” reflects an understanding that, as a fundamental prerequisite for well-being and richness in human lives, health must not be limited by simplistically defined boundaries, be they geographical or economic. Moving forward, we encourage the community of biomedical and social scientists, health economists, health-care professionals, and public health workers to submit papers to us at PLOS that highlight health disparities among low-income and otherwise disadvantaged populations, those who are often forgotten in the world's middle- and high-income countries.

In their recent editorial in JRSM, Liz Wager and Kamran Abbasi boldly suggest that medical journal editors have ‘deserted the moral high ground’ in failing to welcome legal requirements for publicly accessible reporting of clinical trial results.1,2 Trial researchers and sponsors may be interested to know of PLoS Medicine's policy on results disclosure. As set out in a recent editorial,3 we and the other PLoS journals support public disclosure of results of all clinical trials; our guidelines to authors state that: ‘Prior disclosure of results on a public website such as clinicaltrials.gov will not affect the decision to peer review or acceptance of papers in PLoS journals’.4 We hope that editors of journals will pay close attention to Wager and Abbasi's argument that journal articles can provide context, commentary and interpretation of the results of clinical trials; moreover, we propose that journals should provide mechanisms for establishing the quality of research and include similar statements to that of PLoS Medicine in their editorial policies.