Health Risk Analysis – Cox Associates Consulting

Since 1986, Cox Associates Consulting has provided scientific risk analysis and related statistical and engineering consulting services

HEALTH, SAFETY AND ENVIRONMENTAL RISK ANALYSIS PROJECTS COMPLETED BY COX ASSOCIATES

For the National Academies, member of committee advising the Department of Interior’s Bureau of Safety and Environmental Enforcement on Options for Implementing the Requirement of Best Available and Safest Technologies for Offshore Oil and Gas Operations (2013)
For the National Pork Board, quantified the human health risks from swine-associated Methicillin-resistant Staphylococcus Aureus (MRSA) infections (2013)
For the National Pork Board, quantified the human health risks from toxoplasmosis from swine reared in conventional vs. open production systems (2013)
For the National Research Council, member of committee advising the U.S. Air Force on S. Air Force Strategic Deterrence Capabilities in the 21^st Century Security Environment (2012-2013)
For the George Washington University Regulatory Studies Center, reviewed advances in econometric and statistical methods for causal analysis. Applied Granger Causality tests, panel data analysis, and other methods to time series data, and found that changes in temperature, but not changes in particulate matter, are Granger-causes of benefits previously attributed to Clean Air Act regulations. (2012)
For the National Sand and Gravel Association, analyzed spatial distributions of socioeconomic variables and cause-specific mortality rates in California. Demonstrated that regression coefficients describing disease rates as functions of proximity to suspected hazardous sources do not have the causal interpretations ofte assigned to them, but reflect spurious associations due to spatially autocorrelated but statistically independent spatial stochastic processes. (2012)
For the National Pork Board, prepared comments on a Russian risk analysis of tetracycline residues in foods. These comments provided the technical basis for the USG’s position in trilateral trade negotiations with the EU and Russian Federation (2011, 2012)
For The Center for Media and Public Affairs (CMPA) at George Mason University, reassessed a risk-cost-benefit analysis of Clean Air Act Amendment impacts, accounting for uncertainty about causation. (2011)
For the Amerian Petroleum Institute, analyzed the application of income distribution equity indices (such as the Atkins Index) to fair distribution of air pollution health risks. Showed that the Atkins Index and related economic indices of income inequality are not useful for health risk inequality assessment (2011)
For the Institute of Medicine (IOM), Dr.Cox served as a reviewer for the IOM Draft on Scientific Standards for Studies of Modified Risk Tobacco Products, examining the types of biomarker data and other scientific information needed to demonstrate to FDA that new products have reduced risks (2011)
Served as expert reviewer for EPA’s Draft Microbial Risk Assessment Guideline: Pathogenic Microorganisms with Focus on Food and Water (2011)
For the U.S. EPA, served as a member of the Science Advisory Board (SAB) for Dioxin (2010-11)
For the Colorado state police, analyzed the frequency and severity of car accidents by time of day, time of year, driver age and sex, driver behavior (e.g., alcohol use, use of safety devices), and types of air bags and oher equipment. Developed an injury prediction model that successfully predicted risks of injury, given an accident, from less than 20% to over 70%, based on preventable causes. (2011)
For the National Mining Association, developed a statistical critique of a proposed quantitative risk assessment for respirable coal mine dust (2010-11)
For the American Chemistry Council’s Crystalline Silica Panel, modeled exposure-response relationships for inflammation-mediated lung diseases and lung cancer risk caused by exposure to quartz dust and crystalline silica. Presented key results and references to Canadian regulators in August, 2010. Health Canada subsequently proposed to regulate crystalline silica as a threshold carcinogen, breaking new ground in science-based regulatory risk analysis for this compound. (2010)
For the National Pork Board, assessed human health risks of multidrug-resistant “superbug” bacterial infections originating from pigs (2010)
For Philip Morris International, developed a quantitative model of age-specific risks of chronic obstructive pulmonary disease (COPD) as a function of smoking history (2008-2009). Clarified the interaction of molecular biological pathways in forming positive feedback loops that trigger and sustain this disease.
For the National Pork Board, reviewed statistical and causal analyses of infant mortality and livestock production (2009)
For the American Chemistry Council’s Crystalline Silica Panel, critically reviewed draft regulatory risk assessments of crystalline silica as a toxic substance and possible lung carcinogen (2009)
For Alpharma and Phibro Animal Health, assessed potential human health risks from use of tetracycline drugs in food animals (2009)
Member of National Academy of Sciences (NAS) Committee on Methodological Improvements to the Department of Homeland Security’s Biological Agent Risk Analysis. (2006-8) http://www8.nationalacademies.org/cp/CommitteeView.aspx?key=48682
Member of Environmental Protection Agency Science Advisory Board (EPA SAB) on Asbestos.
Member of Institute of Medicine’s (IOM) Committee on Aerospace Medicine and the Medicine of Extreme Environments (2006-8), Committee to Review NASA’s Space Flight Health Standards
For Comcast Cable, worked in partnership with North Highland consulting company to develop a customer churn predictive risk assessment model that successfully predicts which customers are most likely to drop services and accounts – months before the drops occur, while there is still time to intervene. The model was statistically compared to existing commercial predictive models and found to be more than twice as effective in identifying high-risk customers early on.
Delegate to First Session of the Codex Ad Hoc Intergovernmental Task Force on Antimicrobial Resistance held in Seoul, Republic of Korea, 23-26 October 2007.
For Xcel Energy, worked in partnership with North Highland consulting company to develop a credit risk assessment model that predicts which customer accounts are likely to become bad debts six months or more in advance, when early intervention is still possible and profitable (2007)
For Qwest Communications, worked in partnership with North Highland consulting company to analyze the amounts of time that employees spend managing internal communications (e-mails, meetings, conference calls, etc.) and identifying opportunities to improve internal communications efficiency (2006).
For Philip Morris International, developed a quantitative model of age-specific risks of lung cancer as a function of smoking history. Estimated the potential reduction in lung cancer risk for smokers if cadmium were removed from tobacco products. (2005-2007)
For Qwest Communications, worked in partnership with North Highland consulting company to quantify customer interest in and willingness to use improved web portals to manage telecommunications services (2006-7).
For a sand and gravel company, examined the usefulness, for estimating risks and setting prioriries, of aggregate exposure metrics for mixtures of asbestos and non-asbestos fibers and particles (2006)
For a telecommunications equipment manufacturer, created a model to predict the numbers and types of equipment failures expected in future years, based on historical failure data for equipment items manufactured in different years. (2006)
For a grass seed company, assessed the quantitative risks of gene flow from genetically modified grasses into the environment via pollen and seeds (2006). This approach was subsequently adopted by the United States District Court for the District of Columbia as a basis for risk calculations (http://www.centerforfoodsafety.org/pubs/GTBC_Doc_94_Opinion%202-5-07.pdf)
For a homeowner’s association, quantified the probable number and timing of future failures in copper pipes due to thermogalvanic corrosion. The model correctly predicted the near statistical certainty of additional pipe failures (2006).
For the National Research Council of the National Academy of Sciences (NAS), advised on modeling potential failures and threats to spent nuclear fuel rods stored in different types of containers. This work contributed to the 2006 NAS report Safety and Security of Commercial Spent Nuclear Fuel Storage, http://www.nap.edu/openbook/0309096472/html/R4.html.
For a large pharmaceutical company, analyzed Phase 3 clinical trial data and showed that a major drug is highly effective in reversing symptoms of a disease in patients in both the short run (within 1-2 weeks) and over a longer time frame. This statistical analysis of the time course of responses and the clusters of different response histories among patients explained several previously unresolved puzzles and made the meaning of the data clear for company statisticians and decision-makers. (2005)
For a law firm specializing in construction defect litigation, developed an approach to sampling available homes or units to support efficient statistical inference from available data, even when some homes or units cannot be inspected. (2005)
For Phibro Animal Health, developed a systems dynamics model of the evolution of bacterial illnesses and resistance in human and animal populations. (2005/2006)
For the American Chemistry Council, assessed the potential human health risks associated with methyl bromide (2005).
For Philip Morris Intenational, developed new ways to integrate partial knowledge of causal mechanisms of lung carcinogenesis with statistical information (mainly epidemiological and molecular epidemiological data) to obtain quantitative bounds on the fraction of lung cancers that can be prevented by removing specific components of exposure and/or blocking specific causal pathways. (2004-2006)
For the cattle industry group R-CALF, developed a value of information (VOI) model for assessing the economic value of tracking Canadian cattle in the US in light of recent BSE findings (2004).
For the Animal Health Institute, developed a Rapid Risk Rating Technique (RRRT) to quantify the human health impacts of food-borne pathogens and animal antimicrobial uses (1Q-04)
For Elanco Animal Health, served on an Expert Panel to develop a mathematical model of the human health benefits of decreasing microbial loads in food animals (2003-4)
For Phibro Animal Health, developed a quantitative risk assessment of the human health risks and benefits from continued use of virginiamycin in chickens and pigs (2002-4)
For the Animal Health Institute, served on an Expert Panel to review human health risks from animal antibiotics (2002-3); developed a farm-to-fork risk simulation model for Campylobacter risks (2000-2002)
For the U.S. Environmental Protection Agency, served as an external expert reviewer for the EPA’s “Perchlorate Environmental Contamination: Toxicological Review and Risk Characterization” Draft External Review Document (March, 2002).
For the World Health Organization (WHO), served as an external expert reviewer for a Consultation on Campylobacter risk assessment, in Geneva (August, 2001)
For the U.S. Food and Drug Administration (FDA), (a) Reviewed proposed approaches to antimicrobial risk assessment (1999) http://www.fda.gov/cvm/antimicrobial/tonycox/index.htm; and (b) Proposed a decision-analytic alternative to FDA’s threshold approach for managing risks of resistant strains of pathogenic bacteria due to use of antibiotics in animals (2001). The FDA at first strongly rejected Dr. Cox’s advice and testimony on how to do antimicrobial risk assessment correctly (with considerable acrimony, in the context of enrofloxacin litigation), but has subsequently had Dr. Cox visit to discuss several antimicrobial risk assessments, and has sought Dr. Cox’s views on how to do better risk analysis.
For the U.S. EPA, served as expert external reviewer and contributor to Review of Uncertainty and Variability Analysis In IRIS for Eight Substances. http://www.epa.gov/ncea/hlthfx_iris.htm
Created computer simulation models (PBPK and PD) of dose-time-response relations for low-level exposures to chemical carcinogens, for Exxon Biomedical Sciences (EBSI). Developed an artificial intelligence method for improving prediction of likely human chemical carcinogens, also for EBSI.
Created a discrete-event stochastic simulation model of the human health risks associated with Ciprofloxacin resistance in Camplyobacter jejuni induced by use of Enrofloxacin in chickens, for the Animal Health Institute (AHI). http://www.cvmbs.colostate.edu/cveadss/schedule/SchedulePage.htm
Critically reviewed epidemiological studies of diesel exhaust and human lung cancer risk, for the Engine Manufacturers Association.
For the American Petroleum Institute (API), created a computer simulation model of bone marrow and blood cell toxicity caused by cyclophosphamide, an immunosuppressive drug. Designed laboratory experiments to validate the model’s predictions. Analyzed clinical and laboratory data to test model’s predictive validity. Prepared a software release so that other scientists could use the model.
Reviewed literature on air pollution and human lung cancer risks, for the American Petroleum Institute.
Applied adaptive spatial sampling to optimize search and clean-up efforts for remediating residential properties around an abandoned hazardous waste site (for AlliedSignal)
Reassessed human cancer risks from 1,3-butadiene using pharmacokinetic modeling to adjust for interspecies differences in internal doses of epoxybutene (for the Chemical Manufacturers Association)
Reassessed the human leukemia risks from benzene exposure using a physiologically-based pharmacokinetic (PBPK) model to calculate internal dose (for the American Petroleum Association)
Reviewed design of an initiation-promotion experiment for studying the potential carcinogenicity of a rubber additive, for Goodyear Tire and Rubber Company.
Developed a general physiologically-based pharmacokinetic (PBPK) modeling software tool for rapidly developing high-quality PBPK models (with ENSR Consulting and Engineering, Inc.)
Reviewed artificial intelligence approaches to characterizing uncertain health risks using weight of evidence, nonmonotonic, and other uncertainty analysis (for Lawrence Berkeley National Laboratory)
Assessed potential health risks associated with occupational exposure to herbicides among roadside workers, using pharmacokinetic models, for a Fortune 100 chemical manufacturer.
Recommendation of cleanup priorities for a large hazardous waste site in Canada
Developed a prototype computer model for biologically based risk assessment of chemical carcinogen risks, for the Western States Petroleum Association (WSPA) and the American Petroleum Institute (API)
Reviewed new biostatistical and “biologically based” approaches to cancer risk analysis, for the California Department of Health Services
Reviewed regulatory history of benzene risk assessments and of biomathematical approaches to modeling leukemogenesis for the Western Oil and Gas Association and the American Petroleum Institute
Prototype computer modeling of the AIDS epidemic (with Arthur D. Little, Inc.)
Designed a 2-year bioassay experiment for isoprene. Analyzed and reported the resulting experimental data for a multi-client, multinational industry group coordinated by Exxon Biomedical Sciences.
Accident risk analysis and consequence analysis of a petrochemical storage facility in California, for a California-based environmental consulting firm
Implemented a Macintosh version of a physiologically-based pharmacokinetic (PBPK) model for benzene pharmacokinetics and total metabolism in rodents and humans, for the API
Explored new mathematical approaches and conceptual frameworks for dealing with scientific uncertainties in biologically-based risk assessment, for the Western States Petroleum Association (WSPA)
Created an interactive data analysis and graphics package for determining the degree of worker protection provided by different respirators, filters, and face masks (with Arthur D. Little, Inc.)
Microeconomic and applied probability modeling of insurance company business risks for use in tax litigation (with Arthur D. Little, Inc.)
Critically reviewed a transportation risk analysis for liquefied natural gas (LNG) operations in the St. Lawrence seaway.
Reviewed progress since 1985 in using decision analysis for accident risk assessments.
Implemented an experimental “intelligent” data base management system for chemical health effects data bases (with Exxon Biomedical Sciences, Inc.)
Uncertainty analysis of PBPK modeling and risk analyses, accounting for model uncertainties and population heterogeneity, for the American Industrial Health Council.
Developed new statistical techniques to predict cancer risks associated with mineral oils, for Mobil Oil.

Selected Publications

Cox LA, Popken DA, Kaplan AM, Plunkett LM, Becker RA. How well can in vitro data predict in vivo effects of chemicals? Rodent carcinogenicity as a case study. Regulatory Toxicology and Pharmacology. 2016 Feb 13;77:54-64.

Cox LA, Jr. and Goodman JE. Re: “Estimating causal associations of fine particles with daily deaths in Boston.” Letter to the Editor. American Journal of Epidemiology. 2016 Mar 15;183(6):593.

Popken DA, Cox LA Jr. Quantifying human health risks caused by Toxoplasmosis from open system production of swine. Human and Ecological Risk Assessment. 2015 Oct 3; 21(7): 1717-1735

Cox LA Jr, Van Orden DR, Lee RJ, Arlauckas SM, Kautz RA, Warzel AL, Bailey KF, Ranpuria AK. How reliable are crystalline silica dust concentration measurements? Regulatory Toxicology and Pharmacology 2015 Jul 6;73(1):126-136.

Cox LA Jr. 2015. Food microbial safety and animal antibiotics. Chapter 15 in Chen C-Y, Yan X, Jackson CR (Eds). Antimicrobial Resistance and Food Safety: Methods and Techniques. Elsevier, New York.

Cox, LA Jr, Popken DA. Has reducing PM2.5 and ozone caused reduced mortality rates in the United States? Annals of Epidemiology. 2015 Mar; 25(3):162-73.

Cox LA Jr, Popken DA. Quantitative assessment of human MRSA risks from swine. Risk Analysis. 2014 Sep;34(9):1639-50

Cox LA, Popken D, Marty MS, Rowlands JC, Patlewicz G, Goyak KO, Becker RA. Developing scientific confidence in HTS-derived prediction models: Lessons learned from an endocrine case study. Regulatory Toxicology and Pharmacology. 2014 Aug; 69(3):443-50. (Winner, “Best Published Papers in 2014 Demonstrating an Application of Risk Assessment: Top Five Papers” award, Society of Toxicology, Risk Assessment Specialty Section, March, 2015)

Cox, LA Jr. Caveats for causal interpretations of linear regression coefficients for fine particulate (PM2.5) air pollution health effects. Risk Analysis. 2013 Dec;33(12):2111-25.

Cox LA Jr. Improving causal inference in risk analysis. Risk Analysis. 2013 Oct;33(10): 1762-71.

Cox LA Jr. Popken DA, Ricci PF. Warmer is healthier: Effects on mortality rates of changes in average fine particulate matter (PM2.5) concentrations and temperatures in 100 U.S. cities. Regulatory Toxicology and Pharmacology. 2013 Aug;66(3):336-46

Cox LA Jr., Popken DA, Berman W. Causal vs. spurious spatial exposure-response associations in health risk analysis. Critical Reviews in Toxicology 2013. Jan; 43(S1):26-38

Berman W, Cox LA, Popken DA. A cautionary tale: The characteristics of two-dimensional distributions and their effects on epidemiological studies employing an ecological design. Critical Reviews in Toxicology 2013. Jan; 43(S1):1-25

Cox T, Popken D, Ricci PF. Temperature, not fine particulate matter (PM2.5), is causally associated with short-term acute daily mortality rates: Results from one hundred United States cities. Dose-Response. 2012 Dec; 11(3): 319-43

Cox LA Jr. and Singer RS. Confusion over antibiotic resistance: Ecological correlation is not evidence of causation. Foodborne Pathogens and Disease. 2012 Aug;9(8):776.

Cox LA Jr. Reassessing the human health benefits from cleaner air. Risk Analysis 2012 May;32(5):816-29

Cox LA Jr. Why income inequality indexes do not apply to health risks. Risk Analysis 2012. Feb; 32(2): 192-196

Cox LA Jr. Dose-response thresholds for progressive diseases. Dose-Response. 2012;10(2):233-50.

Cox LA Jr. Hormesis for fine particulate matter (PM2.5). Dose-Response 2012; 10(2):209-18.

Cox LA Jr. A causal model of chronic obstructive pulmonary disease (COPD) risk. Risk Analysis. 2011 Jan;31(1):38-62. (Winner, 2011 Best Paper Award, Society for Risk Analysis)