The Navigation Guide

October 2010

The Navigation Guide
An Evidence-Based Tool to Bridge the Gap between Clinical Practice and Environmental Health Science

Patrice Sutton, MPH; Jeanne Conry, MD, PhD; Pablo Rodriguez, MD; Tracey Woodruff, PhD, MPH

Rapidly accumulating evidence indicates that ubiquitous exposure to “everyday” levels of environmental chemicals can manifest in a wide range of adverse health outcomes across the human lifespan and generations.1,2 Approximately 87,000 chemical substances were registered for use in U.S. commerce as of 2006, with about 3,000 chemicals manufactured or imported in excess of 1 million pounds each,3 and 700 new industrial chemicals are introduced into commerce each year. Today, these chemicals are distributed throughout patients’ homes, workplaces, and communities, contaminating food, water, air, and consumer products. Everyone in the U.S. has measurable levels of multiple environmental contaminants.4 While many scientific questions remain, the strength of the evidence is sufficiently high that leading health care professionals and scientists have called for timely action to prevent harm.5-7

How have these calls to action reverberated in the trenches of clinical practice? The scientific evidence linking environmental contaminants and adverse human health impacts is voluminous and largely unfamiliar to practicing clinicians. There is no trusted, ready reference or compendium to consult in order to provide patients with timely, evidence-based advice about their exposure to environmental contaminants (unlike the situation with pharmaceuticals). Hence providing evidence-based anticipatory guidance about environmental exposures is far outside the comfort zone and time constraints of most clinicians. Yet patients armed with Internet printouts are clamoring for advice about topics as wide-ranging as the potential for harm from the chemicals in their babies' bottles to whether their workplace exposure to toxic chemicals will have an adverse impact on their pregnancies. Many more patients may be unaware of the preventable harms they and their families face from toxic substances in their homes, workplaces, and community environments. Health care providers have a professional and ethical responsibility to provide prevention-oriented guidance in all of these situations. By proactively intervening to protect patients from harmful environmental exposures linked to a myriad of chronic diseases and disabilities, health professionals can improve patient health outcomes more broadly.

In an effort to speed the translation of environmental health science into improved patient outcomes, the University of San Francisco's Program on Reproductive Health and the Environment undertook an interdisciplinary collaborative effort to develop the Navigation Guide, a systematic and transparent road map for evaluating the relevant scientific evidence. The Navigation Guide is based on contemporary methods of evidence-based medicine (EBM). The purpose of the Navigation Guide is to build a foundation that can be used to provide the practicing clinician with an easy, transparent, and quick way to incorporate the state of the science, patient values and preferences, and other factors into clinical care decisions.

Perhaps the most unfamiliar aspect of environmental health for the practicing physician is the need to advise patients about their exposures in the absence of human experimental data (i.e., randomized-controlled trials [RCTs]) linking the exposure to a health outcome. When it comes to advising patients regarding their exposure to environmental contaminants, a clinician should not wait for human experimental evidence—it will almost never be available. In the context of preventing adverse exposure to environmental contaminants, clinicians need to take timely action based primarily on scientific evidence from animal (in vivo) and in vitro studies. This can seem counterintuitive, because the use ofin vivo and in vitro studies are not routinely part of daily clinical practice and are often misunderstood by clinicians as “weak” evidence.

However, in vivo and in vitro data are integral to regulatory scrutiny of compounds used every day in clinical practice. Pharmaceuticals are tested for toxicity and to ensure benefits outweigh harms before a physician can decide whether or not to prescribe the drug (Figure). Before a drug can even be tested in humans, the company or sponsor is required to perform in vitro and in vivo laboratory tests to discover how the drug works and whether it's likely to be safe and work well in humans. Only after the substance has undergone toxicity testing can humans be exposed in RCTs. Finally, before a drug is approved for sale, an independent and unbiased review must establish that a drug's health benefits outweigh its known risks. Therefore, in vivo, in vitro, and human experimental evidence—plus an analysis of risks and benefits—have all informed human exposure decisions prior to the substance's entry into the marketplace. Once a drug is on the market, postmarket RCTs are also possible (such as testing the comparative efficacy of two different drugs).

In stark contrast, clinical practice decisions about patient exposure to exogenous substances in the environment must typically be made prior to regulatory scrutiny of a compound and in the absence of risk-benefit analysis, because of our current regulatory and legal structure for governing manufactured chemicals (Figure). Unlike the case with pharmaceuticals, the presence of a product on the shelf at the local chain store does not mean the product has been tested for toxicity and does not mean its benefits and harms have been compared. Advising patients about substances that lack regulatory oversight presents a very different decision context to the practicing clinician. Indeed, the vast majority of chemicals in commercial circulation have entered the marketplace without comprehensive and standardized information on their reproductive or other chronic toxicities.8

Ethical considerations also virtually preclude experimental human data from the evidence stream—one cannot experiment by exposing some people to polluted water and others to clean water and then see what happens. Instead, human evidence in environmental health sciences is collected by observing how exposures are differentially distributed in the real world and measuring health outcomes among populations more (often occupationally) or less exposed. While of scientific import, studies that link workplace and/or community exposures to adverse health outcomes represent a failure of prevention. For example, animal data on the carcinogenicity of a variety of chemicals have preceded as well as predicted later epidemiological observations in humans, and strong evidence exists that experimental results can be extrapolated qualitatively to human subjects.9 Whereas an experimental animal carcinogenic study typically lasts two years, it can take twenty years to get a result from a comparable human study.9 Moreover, the benefits of environmental chemicals are mostly not health related, exposures are unintentional, and they vary and may or may not be significant depending on the toxicity of the agent.

For all of these reasons, to protect their patients from harm related to environmental contaminants, clinicians must take timely action based on the same “upstream” in vivo and in vitro indicators of potential harm that keep (or should keep) toxic drugs with no patient or population benefits off the market. The Navigation Guide is a systematic way to compile, rate, and sort the evidence stream to make it easy and quick for clinicians to confidently do just that.

The Navigation Guide is a systematic, transparent EBM methodology that is a key step in moving the emerging science in environmental health directly, rapidly, and easily into the exam room—where it can make a difference to the health of patients and their families. The urgent need to address the role of the environment on patient health is increasingly gaining traction in state and national professional societies of physicians and other clinical care providers (see related article by Gould and Russell in this issue). Uptake of the Navigation Guide by professional organizations will result in evidence profiles that provide uniform, simple, and transparent practice guidelines.

To this end, the American College of Obstetricians and Gynecologists District IX, which represents more than 5,000 California physicians, is actively engaged in the development of the Navigation Guide to support the clinical practice of its state and national fellows. Likewise, Planned Parenthood Federation of America, whose affiliates serve more than three million women and men per year throughout the U.S., is a key partner in developing the Navigation Guide.

The Navigation Guide is currently in the final stages of development. We anticipate its publication in late 2010 in a peer-reviewed journal. We hope that by 2011 it will begin to provide these and other professional organizations with a currently missing tool in a much larger effort to address the health impacts of widespread patient exposure to toxic substances in the environment.

Patrice Sutton, MPH is a research scientist in the Program on Reproductive Health and the Environment at UCSF. Jeanne Conry, MD, PhD, is chair of the American College of Obstetricians and Gynecologists, District IX, assistant physician in chief of Obstetrics and Gynecology at Kaiser Permanente North Valley. Pablo Rodriguez, MD, is associate chair of obstetrics and gynecology and clinical associate professor in the Department of Obstetrics and Gynecology at Brown Medical School and Women and Infants Hospital of Rhode Island. Tracey Woodruff, PhD, MPH, is associate professor and director of the Program on Reproductive Health and the Environment. Visit http://prhe.ucsf.edu.

References
1. National Academy of Sciences. National Research Council Committee on improving risk analysis approaches used by the U.S. Science and Decisions: Advancing Risk Assessment. 2008: EPA, Washington, D.C.
2. National Research Council. Phthalates and Cumulative Risk Assessment: The Task Ahead. Ed. Committee on the Health Risks of Phthalates. 2008, Washington, D.C.: National Academies Press.
3. EPA. What Is the TSCA Chemical Substance Inventory. 2006 [cited 2007 Apr 4]. Available from http://www.epa.gov/opptintr/newchems/pubs/invntory.htm.
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5. Woodruff TJ et al. Proceedings of the Summit on Environmental Challenges to Reproductive Health and Fertility: Executive summary. Fertil Steril. 2008; 89(2 Suppl):e1-e20.
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7. Diamanti-Kandarakis E et al. Endocrine-disrupting chemicals: An Endocrine Society scientific statement. Endocr Rev. 2009; 30(4):293-342.
8. Wilson MP, Chia DA, Ehlers BC. Green chemistry in California: A framework for leadership in chemicals policy and innovation. 2006; California Policy Research Center, University of California.
9. Zapponi GA, Marcello I, Carere A. Prevention, ethics, and science: Lessons from Lorenzo Tomatis. Ann Ist Super Sanita. 2008; 44(1):8-12.