Equity, diversity, and inclusion at the Global Alliance for Genomics and Health.

A lack of diversity in genomics for health continues to hinder equitable leadership and access to precision medicine approaches for underrepresented populations. To avoid perpetuating biases within the genomics workforce and genomic data collection practices, equity, diversity, and inclusion (EDI) must be addressed. This paper documents the journey taken by the Global Alliance for Genomics and Health (a genomics-based standard-setting and policy-framing organization) to create a more equitable, diverse, and inclusive environment for its standards and members. Initial steps include the creation of two groups: the Equity, Diversity, and Inclusion Advisory Group and the Regulatory and Ethics Diversity Group. Following a framework that we call "Reflected in our Teams, Reflected in our Standards," both groups address EDI at different stages in their policy development process.

Effects of an mHealth voice message service (mMitra) on maternal health knowledge and practices of low-income women in India: findings from a pseudo-randomized controlled trial.

BACKGROUND: Mobile Health (mHealth) is becoming an important tool to improve health outcomes in maternal, newborn and child health (MNCH). Studies of mHealth interventions, have demonstrated their effectiveness in improving uptake of recommended maternal services such as antenatal visits. However, evidence of impact on maternal health outcomes is still limited. METHODS: A pseudo-randomized controlled trial (single blind) was conducted to assess the impact of a voice-message based maternal intervention on maternal health knowledge, attitudes, practices and outcomes over time: Pregnancy (baseline/Time 1); Post-partum (Time 2) and when the infant turned one year old (Time 3). Women assigned to the mMitra intervention arm received gestational age- and stage-based educational voice messages via mobile phone in Hindi and Marathi, while those assigned to the control group did not. Both groups received standard care. RESULTS: Two thousand sixteen women were enrolled. Interviews were conducted with 1516 women in the intervention group and 500 women in the control group at baseline and post-partum. The intervention group performed significantly better than controls on four maternal health practice indicators: receiving the tetanus toxoid injection (OR: 1.6, 95% Confidence Interval (CI): 1.05-2.4, p = 0.028), consulting a doctor if spotting or bleeding (OR: 1.72, 95%CI: 1.07-2.75, p = 0.025), saving money for delivery expenses (OR: 1.79, 95%CI: 1.38-2.33, p = 0.0001), and delivering in hospital (OR: 2.5, 95%CI: 1.49-4.35, p = 0.001). The control group performed significantly better than the intervention group on two practice indicators: resting regularly during pregnancy (OR: 0.7, 95%CI: 0.54-0.88, p = 0.002) and having at-home deliveries attended by a skilled birth attendant (OR: 0.46, 95%CI: 0.23-0.91, p = 0.027). Both groups' knowledge improved from Time 1 to Time 2. Only one knowledge indicator, on seeking medical care during pregnancy, was statistically increased in the intervention group compared to controls. Anemia status at or near the time of delivery was unable to be assessed due to missing data from maternal health cards. CONCLUSIONS: This study provides evidence that in low-resource settings, mobile voice messages providing tailored and timed information about pregnancy can positively impact maternal health care practices proven to improve maternal health outcomes. Additional research is needed to assess whether voice messaging can motivate behavior change better than text messaging, particularly in low literacy settings. TRIAL REGISTRATION: The mMitra impact evaluation is registered with ISRCTN under Registration # 88968111, assigned on 6 September 2018 (See https://www.isrctn.com/ISRCTN88968111).

The Impact of an mHealth Voice Message Service (mMitra) on Infant Care Knowledge, and Practices Among Low-Income Women in India: Findings from a Pseudo-Randomized Controlled Trial.

Objectives mHealth interventions for MNCH have been shown to improve uptake of antenatal and neonatal services in low- and middle-income countries (LMICs). However, little systematic analysis is available about their impact on infant health outcomes, such as reducing low birth weight or malnutrition among children under the age of five. The objective of this study is to determine if an age- and stage-based mobile phone voice messaging initiative for women, during pregnancy and up to 1 year after delivery, can reduce low birth weight and child malnutrition and improve women's infant care knowledge and practices. Methods We conducted a pseudo-randomized controlled trial among pregnant women from urban slums and low-income areas in Mumbai, India. Pregnant women, 18 years and older, speaking Hindi or Marathi were enrolled and assigned to receive mMitra messages (intervention group N = 1516) or not (Control group N = 500). Women in the intervention group received mMitra voice messages two times per week throughout their pregnancy and until their infant turned 1 year of age. Infant's birth weight, anthropometric data at 1 year of age, and status of immunization were obtained from Maternal Child Health (MCH) cards to assess impact on primary infant health outcomes. Women's infant health care practices and knowledge were assessed through interviews administered immediately after women enrolled in the study (Time 1), after they delivered their babies (Time 2), and after their babies turned 1 year old (Time 3). 15 infant care practices self-reported by women (Time 3) and knowledge on ten infant care topics (Time 2) were also compared between intervention and control arms. Results We observed a trend for increased odds of a baby being born at or above the ideal birth weight of 2.5 kg in the intervention group compared to controls (odds ratio (OR) 1.334, 95% confidence interval (CI) 0.983-1.839, p = 0.064). The intervention group performed significantly better on two infant care practice indicators: giving the infant supplementary feeding at 6 months of age (OR 1.4, 95% CI 1.08-1.82, p = 0.009) and fully immunizing the infant as prescribed under the Government of India's child immunization program (OR 1.531, 95% CI 1.141-2.055, p = 0.005). Women in the intervention group had increased odds of knowing that the baby should be given solid food by 6 months (OR 1.89, 95% CI 1.371-2.605, p < 0.01), that the baby needs to be given vaccines (OR 1.567, 95% CI 1.047-2.345, p = 0.028), and that the ideal birth weight is > 2.5 kg (OR 2.279, 95% CI 1.617-3.213, p < 0.01). Conclusions for Practice This study provides robust evidence that tailored mobile voice messages can significantly improve infant care practices and maternal knowledge that can positively impact infant child health. Furthermore, this is the first prospective study of a voice-based mHealth intervention to demonstrate a positive impact on infant birth weight, a health outcome of public health importance in many LMICs.

The Elusive Path Toward Measuring Health Outcomes: Lessons Learned From a Pseudo-Randomized Controlled Trial of a Large-Scale Mobile Health Initiative.

Mobile health (mHealth) offers new opportunities to improve access to health services and health information. It also presents new challenges in evaluating its impact, particularly in linking the use of a technology intervention that aims to improve health behaviors with the health outcomes that are impacted by changed behaviors. The availability of data from a multitude of sources (paper-based and electronic) provides the conditions to facilitate making stronger connections between self-reported data and clinical outcomes. This commentary shares lessons and important considerations based on the experience of applying new research frameworks and incorporating maternal and child health records data into a pseudo-randomized controlled trial to evaluate the impact of mMitra, a stage-based voice messaging program to improve maternal, newborn, and child health outcomes in urban slums in India.

The continuing saga of patents and non-invasive prenatal testing.

OBJECTIVE: This paper examines the Intellectual Property (IP) landscape for non-invasive prenatal testing (NIPT) in three key regions: the United States; Europe, with particular focus on the United Kingdom; and Australia. METHOD: We explore the patent law issues against the commercial and healthcare environment in these regions and consider the implications for development and implementation of NIPT. RESULTS: There are many patents held by many parties internationally, with litigation over these patents ongoing in many countries. Importantly, there are significant international differences in patent law, with patents invalidated in the USA that remain valid in Europe. Despite the many patents and ongoing litigation, there are multiple providers of testing internationally, and patents do not appear to be preventing patient access to testing for those who can pay out of pocket. CONCLUSION: The patent situation in NIPT remains in a state of flux, with uncertainty about how patent rights will be conferred in different jurisdictions, and how patents might affect clinical access. However, patents are unlikely to result in a monopoly for a single provider, with several providers and testing technologies, including both public and private sector entities, likely to remain engaged in delivery of NIPT. However, the effects on access in public healthcare systems are more complex and need to be monitored.

Toward an Ethically Sensitive Implementation of Noninvasive Prenatal Screening in the Global Context.

Noninvasive prenatal screening using cell-free DNA, which analyzes placental DNA circulating in maternal blood to provide information about fetal chromosomal disorders early in pregnancy and without risk to the fetus, has been hailed as a potential "paradigm shift" in prenatal genetic screening. Commercial provision of cell-free DNA screening has contributed to a rapid expansion of the tests included in the screening panels. The tests can include screening for sex chromosome anomalies, rare subchromosomal microdeletions and aneuploidies, and most recently, the entire fetal genome. The benefits of this screening tool are generally framed, by both providers and commercial laboratories, as enhancing reproductive autonomy and choice by providing an earlier, simpler, and more accurate screening while potentially reducing the need for invasive follow-up testing. The majority of the literature has explored these issues empirically or conceptually from a European or North American vantage point, one that assumes normative priorities such as individual reproductive autonomy and the clinical availability of maternal health care or prenatal screening programs within which cell-free DNA screening is offered. While its implementation has raised both challenges and opportunities, very little is known about real-world experiences and the implications of the rapid introduction of cell-free DNA screening outside of North America and Europe, especially in low- and middle-income countries. To begin addressing this gap in knowledge, we organized a four-day international workshop to explore the ethical, legal, social, economic, clinical, and practical implications of the global expansion of cell-free DNA screening. We describe eight key insights that arose from the workshop.

"The Top Priority Is a Healthy Baby": Narratives of Health, Disability, and Abortion in Online Pregnancy Forum Discussions in the US and China.

The introduction of cell-free DNA prenatal genetic screening has rekindled discussion of ethical and social questions surrounding prenatal testing, perceptions of disability, and abortion. The growing use of prenatal genetic screening presents a unique opportunity to assess decision-making around new methods of prenatal testing; especially as there is little available research comparing individual and cultural differences that affect a pregnant woman's decision-making on prenatal testing. We performed a content analysis of online pregnancy forums in the United States and Mainland China. Content from January 2012 to December 2013 was identified through search methodologies and refined to remove duplication. China-based content was translated by a native Mandarin speaker. We used qualitative analysis methods to identify common themes in the dataset. There were 333 English responses and 519 Mandarin responses. Three main themese were identified in the data: decision making factors, attitude towards the pregnancy, and attitudes towards abortion. Women's narratives reflected how broader social forces can have an impact on intimate personal decision-making. Women in the Mandarin dataset evoked stronger narratives of community and/or family decision-making in pregnancy and were more accepting of the possibility of abortion in the event of a finding of fetal abnormality. Narrative in the English dataset more frequently evoked ideas of unconditional love, regardless of fetal diagnosis, but also acknowledged much stronger support services for individuals with disability and less awareness of stigma. These results highlight the necessity of awareness around how broader cultural and social factors can consciously or unconsciously impact women's decisions and highlight potential focus areas for future counseling efforts.

Barriers to clinical adoption of next generation sequencing: Perspectives of a policy Delphi panel.

This research aims to inform policymakers by engaging expert stakeholders to identify, prioritize, and deliberate the most important and tractable policy barriers to the clinical adoption of next generation sequencing (NGS). A 4-round Delphi policy study was done with a multi-stakeholder panel of 48 experts. The first 2 rounds of online questionnaires (reported here) assessed the importance and tractability of 28 potential barriers to clinical adoption of NGS across 3 major policy domains: intellectual property, coverage and reimbursement, and FDA regulation. We found that: 1) proprietary variant databases are seen as a key challenge, and a potentially intractable one; 2) payer policies were seen as a frequent barrier, especially a perceived inconsistency in standards for coverage; 3) relative to other challenges considered, FDA regulation was not strongly perceived as a barrier to clinical use of NGS. Overall the results indicate a perceived need for policies to promote data-sharing, and a desire for consistent payer coverage policies that maintain reasonably high standards of evidence for clinical utility, limit testing to that needed for clinical care decisions, and yet also flexibly allow for clinician discretion to use genomic testing in uncertain circumstances of high medical need.

Impact of the increased adoption of prenatal cfDNA screening on non-profit patient advocacy organizations in the United States.

The 'Stakeholder Perspectives on Noninvasive Prenatal Genetic Screening' Symposium was held in conjunction with the 2015 annual meeting of the International Society for Prenatal Diagnosis. During the day-long meeting, a panel of patient advocacy group (PAG) representatives discussed concerns and challenges raised by prenatal cell-free DNA (cfDNA) screening, which has resulted in larger demands upon PAGs from concerned patients receiving prenatal cfDNA screening results. Prominent concerns included confusion about the accuracy of cfDNA screening and a lack of patient education resources about genetic conditions included in cfDNA screens. Some of the challenges faced by PAGs included funding limitations, lack of consistently implemented standards of care and oversight, diverse perspectives among PAGs and questions about neutrality, and lack of access to training and genetic counselors. PAG representatives also put forward suggestions for addressing these challenges, including improving educational and PAG funding and increasing collaboration between PAGs and the medical community. © 2016 John Wiley & Sons, Ltd.

Noninvasive Prenatal Genetic Testing: Current and Emerging Ethical, Legal, and Social Issues.

Noninvasive prenatal genetic testing (NIPT) for chromosomal aneuploidy involving the analysis of cell-free fetal DNA became commercially available in 2011. The low false-positive rate of NIPT, which reduces unnecessary prenatal invasive diagnostic procedures, has led to broad clinician and patient adoption. We discuss the ethical, legal, and social issues raised by rapid and global dissemination of NIPT. The number of women using NIPT is anticipated to expand, and the number of conditions being tested for will continue to increase as well, raising concerns about the routinization of testing and negative impacts on informed decision making. Ensuring that accurate and balanced information is available to all pregnant women and that access to NIPT is equitable will require policy guidance from regulators, professional societies, and payers. Empirical evidence about stakeholders' perspectives and experiences will continue to be essential in guiding policy development so that advances in NIPT can be used effectively and appropriately to improve prenatal care.

Intellectual property rights and challenges for development of affordable human papillomavirus, rotavirus and pneumococcal vaccines: Patent landscaping and perspectives of developing country vaccine manufacturers.

The success of Gavi, the Vaccine Alliance depends on the vaccine markets providing appropriate, affordable vaccines at sufficient and reliable quantities. Gavi's current supplier base for new and underutilized vaccines, such as the human papillomavirus (HPV), rotavirus, and the pneumococcal conjugate vaccine is very small. There is growing concern that following globalization of laws on intellectual property rights (IPRs) through trade agreements, IPRs are impeding new manufacturers from entering the market with competing vaccines. This article examines the extent to which IPRs, specifically patents, can create such obstacles, in particular for developing country vaccine manufacturers (DCVMs). Through building patent landscapes in Brazil, China, and India and interviews with manufacturers and experts in the field, we found intense patenting activity for the HPV and pneumococcal vaccines that could potentially delay the entry of new manufacturers. Increased transparency around patenting of vaccine technologies, stricter patentability criteria suited for local development needs and strengthening of IPRs management capabilities where relevant, may help reduce impediments to market entry for new manufacturers and ensure a competitive supplier base for quality vaccines at sustainably low prices.

Global perspectives on clinical adoption of NIPT.

OBJECTIVE: The goals of this study were to assess global trends in clinical implementation of noninvasive prenatal testing (NIPT), as commercial tests are marketed increasingly worldwide, and to identify potential challenges for current or future use. METHODS: We surveyed clinicians from 46 countries about the availability of NIPT, their experiences with using NIPT, and their views on clinical, ethical, and legal issues affecting implementation in their countries. RESULTS: Forty-nine respondents from 28 countries completed the survey. The majority reported that NIPT is available in their country (n = 43) and that they offer NIPT in their current practice (n = 38). Eighteen respondents from 14 countries reported that there are plans to introduce NIPT into routine prenatal care in their country. Test prices varied widely, ranging from $350 to $2900, and several respondents observed that high test prices limited or restricted widespread use of NIPT. Responses varied both across and within countries regarding who is offered NIPT and what the overall screening protocol should be. CONCLUSION: This study provides a snapshot of current use and experiences with NIPT globally. It also highlights differences in service provision that exists both across and within countries, emphasizing the need for developing national and international implementation guidelines for NIPT.

Non-invasive prenatal testing: a review of international implementation and challenges.

Noninvasive prenatal genetic testing (NIPT) is an advance in the detection of fetal chromosomal aneuploidies that analyzes cell-free fetal DNA in the blood of a pregnant woman. Since its introduction to clinical practice in Hong Kong in 2011, NIPT has quickly spread across the globe. While many professional societies currently recommend that NIPT be used as a screening method, not a diagnostic test, its high sensitivity (true positive rate) and specificity (true negative rate) make it an attractive alternative to the serum screens and invasive tests currently in use. Professional societies also recommend that NIPT be accompanied by genetic counseling so that families can make informed reproductive choices. If NIPT becomes more widely adopted, States will have to implement regulation and oversight to ensure it fits into existing legal frameworks, with particular attention to returning fetal sex information in areas where sex-based abortions are prevalent. Although there are additional challenges for NIPT uptake in the developing world, including the lack of health care professionals and infrastructure, the use of NIPT in low-resource settings could potentially reduce the need for skilled clinicians who perform invasive testing. Future advances in NIPT technology promise to expand the range of conditions that can be detected, including single gene disorders. With these advances come questions of how to handle incidental findings and variants of unknown significance. Moving forward, it is essential that all stakeholders have a voice in crafting policies to ensure the ethical and equitable use of NIPT across the world.

Patents and genome-wide DNA sequence analysis: is it safe to go into the human genome?

Some claims in patents on individual genes and methods of detecting variations appear to be infringed by whole-genome and all-exome sequencing and genomic analysis. But what is the real risk of infringement liability? The risk is probably low. This is partly because it will rarely make sense to sue, but also because the patent-holder may well lose if they do sue. Courts have recently narrowed standards of patentable subject matter, invalidating broad method claims and DNA-based claims for sequences that would be found in nature. Moreover, claims broad enough to cover WGS are likely to be invalid on other grounds, and not worth risking a lawsuit to enforce.

Do recent US Supreme Court rulings on patenting of genes and genetic diagnostics affect the practice of genetic screening and diagnosis in prenatal and reproductive care?

Thousands of patents have been awarded that claim human gene sequences and their uses, and some have been challenged in court. In a recent high-profile case, Association for Molecular Pathology, et al. v. Myriad Genetics, Inc., et al., the US Supreme Court ruled that genes are natural occurring substances and therefore not patentable through 'composition of matter' claims. The consequences of this ruling will extend well beyond ending Myriad's monopoly over BRCA testing and may affect similar monopolies of other commercial laboratories for tests involving other genes. It could also simplify intellectual property issues surrounding genome-wide clinical sequencing, which can generate results for genes covered by intellectual property. Non-invasive prenatal testing (NIPT) for common aneuploidies using cell-free fetal (cff) DNA in maternal blood is currently offered through commercial laboratories and is also the subject of ongoing patent litigation. The recent Supreme Court decision in the Myriad case has already been invoked by a lower district court in NIPT litigation and resulted in invalidation of primary claims in a patent on currently marketed cffDNA-based testing for chromosomal aneuploidies.

Noninvasive prenatal testing goes global.

Noninvasive prenatal genetic testing is becoming available worldwide--particularly in low- and middle-income countries--but practical and ethical challenges must be overcome.

Preliminary perspectives on DNA collection in anti-human trafficking efforts.

Forensic DNA methodologies have potential applications in the investigation of human trafficking cases. DNA and relationship testing may be useful for confirmation of biological relationship claims in immigration, identification of trafficked individuals who are missing persons, and family reunification of displaced individuals after mass disasters and conflicts. As these applications rely on the collection of DNA from non-criminals and potentially vulnerable individuals, questions arise as to how to address the ethical challenges of collection, security, and privacy of collected samples and DNA profiles. We administered a survey targeted to victims' advocates to gain preliminary understanding of perspectives regarding human trafficking definitions, DNA and sex workers, and perceived trust of authorities potentially involved in DNA collection. We asked respondents to consider the use of DNA for investigating adoption fraud, sex trafficking, and post-conflict child soldier cases. We found some key differences in perspectives on defining what qualifies as "trafficking." When we varied terminology between "sex worker" and "sex trafficking victim" we detected differences in perception on which authorities can be trusted. Respondents were supportive of the hypothetical models proposed to collect DNA. Most were favorable of DNA specimens being controlled by an authority outside of law enforcement. Participants voiced concerns focused on privacy, misuse of DNA samples and data, unintentional harms, data security, and infrastructure. These preliminary data indicate that while there is perceived value in programs to use DNA for investigating cases of human trafficking, these programs may need to consider levels of trust in authorities as their logistics are developed and implemented.