Increasing amounts of research in medicine and public health are being conducted in the developing world, yet critical questions remain regarding whether and to what degree these studies adhere to ethical standards. As described more fully below, at present, approximately 5% of the world’s medical journals have stated that they follow guidelines of the International Council Medical Journal Editors (ICMJE) that stipulate that the authors include a statement concerning institutional review board (IRB) review either in the article or in a cover letter to the editors.1
However, several studies have suggested that published articles do not always include this information.2
Many questions remain concerning whether studies conducted in the developing world have in fact obtained IRB review, and whether published articles reporting on that research in fact mention whether IRB approval was obtained. It is important that authors include this information, since science and public trust of science are crucial, especially among groups who may be wary of research.3
Without including this information, readers have no way of knowing whether ethical standards were in fact followed. Given scandals – both documented and alleged – involving violations of patients’ rights in both the developed and the developing world,4
such transparency and assurance are essential. Thus, if a substantial proportion of articles are found currently to fail to disclose this information, arguably, consideration should be given to requiring that all journals mandate that all published articles reporting on human subjects research mention, in-print, whether IRB approval was or was not obtained (and if not, why not).
The amount of research in developing countries continues to rise. More than half of all FDA-regulated clinical trials in 2010 were conducted outside of the US.5
In 2006, of active FDA-regulated researchers, 41% worked outside the US.6
In 2007, of industry funded phase-III trials on Clinicaltrials.gov
, only 44% were based in the US.7
Such research may stem from global health priorities, and/or permit researchers to increase sample sizes for studies at lower costs. 8
Yet the globalization of this research raises important ethical questions, such as those concerning the possible exploitation of vulnerable populations.9
International studies may require approval by more than one IRB or research ethics committee (REC), but we know of only one study that has compared IRBs in the US to IRBs or RECs in the developing world.10
Documentation of having obtained IRB or REC approval is important, as it is the ‘final check in ensuring the highest scientific and ethical standards and a necessary step in protecting research subjects and maintaining public trust’ in the process of medical research.11
However, crucial basic information, such as how often research conducted in the developing world is in fact reviewed by an IRB or REC, and, in what way (that is, to what extent and with what quality of review) remain unknown. Unfortunately, to assess these questions requires substantial resources, of time and money, which have proven to be insurmountable obstacles. Yet, there are vital initial questions in this realm that can be readily addressed and, as described below, possibly shed light on critical aspects of these issues – specifically, exploration of how often journal articles reporting on research conducted in various developing countries even mention IRB/REC approval, and what factors may be involved.
The International Committee of Medical Journal Editors (ICMJE), in 1997, altered its requirements for IRB approval reporting in biomedical journals, necessitating that authors indicate if the research adhered to the ethical standards of the appropriate institutional or national body.12
Over 700 journals state online that they follow ICMJE requirements. Editors from 12 journals form the membership itself. A study of the 103 English-language journals included in the Abridged Index Medicus showed IRB approval requirements increased between 1995 and 2005 from 45% to 76% and was associated with higher impact factors of the journals.13
A few articles in the New England Journal of Medicine
, the Journal of the American Medical Association
and elsewhere have begun exploring whether published journal articles indeed mention IRB approval,14
but many questions about it remain. Just after 1997, in industrialized countries, the failure to report IRB approval and informed consent appeared to decrease somewhat, but then appeared to increase to pre-1997 levels.15
Previously, for example, failure to mention IRB approval was 100% in 1978 among 24 resuscitation research articles16
and 71% among clinical trial articles published in ‘top’ medical journals between 1993 and 1995.17
From immediately before 1997 (1995-1996) to immediately after (1998-1999), failure to mention IRB approval in articles published in the top five medical journals whose editors are members of the ICMJE fell from 31% to 18%.18
However, a 2003 follow up study showed that failure to report IRB approval rose again to 31% of articles in these same top journals.19
Failures to report IRB approval have been documented in not only ‘top’ medical journals,20
but specialty journals, with rates of 29% in 2001 and 24% in 1994 in anesthesia and critical care medicine, respectively.21
In anesthesiology journals, the type of study (for example, trials versus observational studies), and the specific journal were significantly associated with documentation of IRB approval.
Yet this research on documentation of IRB approval has focused on studies conducted in industrialized countries, and has explored to a far less degree research conducted in the developing world. We found only two studies that explicitly examined articles reporting on research in the developing world. A 2008 study reported that 62% of Sri Lankan research articles did not mention IRB/REC approval.22
Yet, this study did not examine other factors that may be associated with reporting of IRB approval – for example, author affiliations or type of journal.23
A 2008 study found that approximately 70% of research papers published in two Indian pediatrics journals did not report IRB/REC approval. But this study had several limitations, studying only two journals from the same country, and did not distinguish between primary investigators from India as opposed to elsewhere in the world.24
In one study of critical care journals, articles on research conducted in the US compared to elsewhere in the world did not differ in mentioning of IRB approval,25
though the authors of this study did not identify the locations outside the US (for example, developed or developing countries), and thus did not address the particular ethical issues faced in developing world research.
In short, we have found no study that examined how often published research articles mention ethical issues in more than one developing country, or assessed several critical factors that may be involved.
Clearly, what is most important is whether IRB/REC approval occurs, not simply whether it is documented in the published article. On the one hand, a critic could potentially argue that published articles do not need to attest to such review, and that nothing more could or should be done to increase the proportion of articles that mention such review. The National Institutes of Health (NIH), Food and Drug Administration (FDA), and World Health Organization (WHO) all state that they require a statement and/or documentation of IRB approval. Hence, one might allege, whether published articles mention it is utterly irrelevant and inconsequential.
Yet, on the other hand, importantly, not all research conducted in the developing world is funded by, and/or submitted to, the NIH, FDA or WHO. Rather, many research studies may be investigator-initiated, funded by private foundations, other governmental agencies, or have little, if any external funding. However, such studies nonetheless involve human subjects whose rights need to be protected.
Moreover, the effectiveness of any policy or guideline depends on not only whether it is enacted by a bureaucratic entity, but whether and how it is implemented by multiple stakeholders, and to what extent and how they in fact follow it. Numerous challenges exist in importing IRBs/RECs into the developing world,26
and critics have questioned whether Western Ethical Imperialism is occurring.27
Some researchers may simply want to check a box that IRB review has or has not occurred, as if it were merely an administrative formality. Yet, the complex political, social, cultural, economic and historical contexts of diverse regions in developing world countries make it imperative to try to shed some light, if possible, on the issues and factors that may be involved.
It is wholly unknown what proportion of published studies are in fact approved by an IRB, and what the extent and quality of the IRB reviews are – for example, who reviews the protocol (that is, a private or for profit IRB, a host country and/or a sponsor country IRB), and of what the reviews consist. IRBs differ significantly in their decisions and interpretations of basic ethical principles.28
Furthermore, researchers do not always follow ethical principles and guidelines. Scandals involving violations of research ethics have occurred in both the US and the developing world.29
Hence, ensuring that research meets the highest possible ethical standards is vital. In this effort, public transparency and documentation are crucial. A paper in Nature
entitled ‘Scientists Behaving Badly’ reported that up to 33% of US researchers admitted to engaging in ‘questionable behavior that threatens the integrity of science’.30
Of respondents, 7.6% reported ‘circumventing certain minor aspects of human-subject requirements’.31
The percentage of researchers ‘behaving badly’ in the developing world remains unknown. Hence, explicit documentation of compliance with ethical standards in published articles can be helpful, potentially enhancing such compliance.
In addition, it is crucial to recognize that 95% of medical journals have not signed onto ICMJE’s guidelines. Though 694 journals have listed themselves on ICMJE’s website as following its guidelines, these publications constitute only approximately 5% of the total number of active medical journals in the world.32
Other journals may also follow these ethical standards, but the nature and implementation of these journals’ ethical requirements may vary widely.33
It is also unknown whether journals that have signed onto ICMJE guidelines in fact follow these guidelines, and if so, how and to what degree.
Given these challenges in research ethics, requiring that published articles mention IRB approval may be important, in and of itself, in allowing readers to judge for themselves the scientific and ethical standards followed by the investigators, and in enhancing the likelihood that researchers will indeed obtain appropriate IRB approval.
Clearly, several broad questions remain about IRB review and will require large scale research efforts to address fully. In the meantime, any data that might be available and shed any light on these issues, in any way, may be helpful.
Thus, we decided to explore how often articles on research conducted in four developing world countries mention IRB/REC approval (referred to below as ‘IRB approval’), and what factors may be associated with differences that emerge. We focused on HIV, since it is a vital realm of research in both developed and developing countries, as the pandemic affects approximately 38.6 million people worldwide.34
This research examines vulnerable and stigmatized populations – making human subject protections especially important – and has triggered controversies.35
We have explored elsewhere, whether articles reporting research that was sponsored by one country, but conducted in another country, had listed dual or single IRB/REC approval, and if so, from what country or countries.36
But critical questions emerge as to whether research conducted in the developing world more broadly, regardless of the source of sponsorship, if any, lists any such IRB/REC approval, and what factors might be involved. Such articles often do not list sources of funding,37
but how often they mention any IRB/REC review is unknown.