Review of NASA's Evidence Reports on Human Health Risks: 2017 Letter Report (2018)

RISK OF ADVERSE HEALTH OUTCOMES AND DECREMENTS IN PERFORMANCE DUE TO IN-FLIGHT MEDICAL CONDITIONS

The introductory section of the evidence report Risk of Adverse Health Outcomes and Decrements in Performance Due to In-Flight Medical Conditions succinctly states: “Given that medical conditions/events will occur during human spaceflight missions, there is a possibility of adverse health outcomes and decrements in performance in mission and for long term health” (Antonsen et al., 2017, p. 5). NASA, through HRP’s Exploration Medical Capabilities Element, is specifically concerned with establishing evidenced-based methods of monitoring and maintaining astronaut health. Essential to completing this task is the advancement in techniques that identify, prevent, and treat any health threats that might occur during space missions.

The evidence report is organized to discuss the risks and challenges of designing medical capabilities for exploration missions. Constraints include those on designing habitats, communications, telemetry, data, and the lack of evacuation capability. A section noting the utility of a Concept of Operations (ConOps) for a Transit Mission to Mars (emphasis added) is used to highlight the fact that such a ConOps does not currently exist, though relevant work that is available includes the 2009 Space Medicine Exploration Medical Condition List, the predictive Integrated Medical Model, an Exploration Medical Conditions Concept of Operations and Exploration Medical Capability Element updated in 2014, and Telemedicine Operational Concepts for Human Exploration Missions, also from 2014. The report notes some of the ethical considerations resulting from medical capability constraints and discusses the application of the principles of protection of the rights and welfare of research subjects.

In discussing exploration mission medical systems, the evidence report focuses on modeling and predicting risks, the components of the medical mission (with an extensive discussion of onboard pharmaceuticals, including the relevant results from research done on shelf life, bioavailability, and radiation effects), and system capabilities (with discussions on maintaining musculoskeletal and cardiovascular conditioning and the potential need for rehabilitation functions for long-duration missions). The report also discusses the need for autonomous decision support and for onboard knowledge resources to support diagnosis and treatment. The report further includes a detailed discussion of risk miti-

gation that highlights three conditions deemed to be high risk for exploration-class missions—bone fracture, dust exposure, and renal stone formation—as well as of mitigating risk through the selection of a physician astronaut, continuing education, and just-in-time training for medical procedures. The report concludes with a listing of 13 research knowledge gaps.

Does the Evidence Report Provide Sufficient Evidence, as Well as Sufficient Risk Context, That the Risk Is of Concern for Long-Term Space Missions?

At a basic level, the expectation of illnesses and injuries occurring during an extended-duration mission and the need to diagnose and treat these effectively are self-evident. In that regard, it is impossible to imagine the risk of inadequate medical capabilities would not be of concern. However, this is such a broad topic that the evidence report is a somewhat eclectic sampler of topics relevant to medical conditions expected to be associated with exploration-class missions rather than a comprehensive overview. The strengths of this report include the thorough description of NASA’s exploration medical capabilities work, the discussion of constraints regarding medical capabilities, the depth and detail of data provided on pharmaceutical bioavailability and shelf life, the summary of approaches to training and simulation, and the narrative on planetary dust. However, these strengths are offset to some extent by substantial issues of risk context that are at best unclear, and at worst confusing.

The lack of clarity begins with the report’s title, which focuses on in-flight medical conditions, when a more accurate title might encompass the entire mission; the report would then logically be divided into mission phases, only some of which would be in flight. The lack of clarity is also reflected in the text, as some of the contributing authors have clearly narrowly interpreted the topic as being restricted solely to a transit mission without a surface landing. In contrast, other NASA Mars Expedition Design Reference Missions detail a descent to the Mars surface and a shorter or longer-term stay before returning (Drake, 2009; NASA, 2015). The failure to acknowledge the range of potential missions leads to inconsistencies in the report’s content. For example, sections of the report focus exclusively on the two transit, or cruise, phases of a human planetary expedition, but the report also includes a surface risk (i.e., dust exposure) among the three risks selected for more detailed discussion, and

it cites experience from analogous conditions on Earth, such as Antarctic research stations. The report ignores nearly all of the medical risks of a potential long-term surface operation.

The expectation of the committee, which would likely mirror the expectation of most non-specialist readers, is that medical capability should be viewed as an end-to-end continuum for exploration-class missions. Because none of the other risk reports address this topic holistically, there is an opportunity for this report to provide that broad perspective, and thus the committee is concerned about the narrow scope of the report as written. This or another risk report (such as the evidence report on the risk of injury due to EVA operations [Chappell et al., 2017]) should address the numerous potential work tasks and risks of Mars surface operations, which include construction, the operation of excavation equipment, maintenance inside and outside the surface habitat, mechanized traverses to conduct geological/biological research, the deployment of solar and possibly nuclear electric facilities and distribution busses, the operation of well-drilling rigs and coring devices, and the loading of fuel produced on the surface to propel the ascent vehicle to Mars orbit at the end of the surface phase.

The types of tasks that will be conducted during surface operations are dangerous when conducted on Earth and frequently result in serious injury; the danger and risk of injury will be compounded on the surface of Mars. A vast array of health and medical conditions could be faced during a human expedition to Mars, as discussed throughout the full set of evidence reports, including trauma incidents, decompression sickness resulting from suit punctures, dental emergencies, radiation incidents, electrocution, hazardous materials exposure, and the death of a crew member. The expedition physician must be prepared with training and tools to treat all of these situations, and more.

Viewing these requirements as distinct from those of the transit phases of a Mars mission seems illogical and prone to result in inefficiencies and redundancies in HRP’s research and development agenda and in any operational decisions made on the basis of knowledge generated by HRP efforts.

The report should also emphasize preventive and health promotion approaches to spaceflight medical capabilities. The committee notes that the proactive optimization of human functions, not simply diagnosing and treating diseases or outcomes, should be at the center of the design of health-related capabilities for long-duration missions.

The committee believes that the understanding of risk context would be strengthened by addition or revision of the following:

• The addition of quantitative estimates of risks of specific conditions to bolster the largely qualitative assertions made in the report. The committee noted that risk estimates are available in many of the references cited by the report, and some are available in Appendix Table 1, but these have not been incorporated into the narrative report text. Similarly, the inclusion of quantitative data from analog environments would strengthen the report.
• A discussion of trauma, which is statistically the most frequently encountered health condition to date. This should include space suit trauma and should address trauma outside and inside the suit, incorporating the lessons learned in this area from work already done by NASA, with cross-references to other relevant evidence reports (e.g., Chappell et al., 2017). Candidate scenarios in this regard would also include surgical emergencies, such as a comminuted fracture and surgical abdomen due to a perforated viscus (e.g., perforated ulcer).
• Additional data and discussion about the prevalence of similar risks and mitigation strategies in partial gravity environments, as the nature of the health risks in a number of areas is reasonably well understood in microgravity.
• Additional content in the areas of cardiovascular diseases, psychology, and behavior.
• Descriptions of additional diagnostic modalities of imaging other than ultrasound.
• A revision of the assessment of commercially available electronic health record systems to highlight instead the unique functional requirements of a system that provides both decision support and the clinical documentation of care for exploration-class missions.
• Clarification of the discussions regarding personalized medicine and an acknowledgment of the need for further research in this area. The report notes the following:

The committee believes that making “personalized medicine” synonymous with the use of genetic and genomic information does not do NASA a service, since there are many aspects of the effective personalization of risk assessment, customized countermeasures optimized for individuals, and modifications of therapy that do not depend on genomic data. An example is using the monitoring of urinary calcium to target exercise and pharmaceutical countermeasures to individuals showing patterns of excretion associated with future health problems, rather than having the same countermeasures done by everyone. Because all of the commonly used terms, such as “individualized” or “personalized medicine,” and “precision medicine,” are unclear with respect to whether they incorporate genetic and genomic data, the committee recommends that HRP simply and explicitly describe genetic data in any context in which they are used or investigated and not rely on there being a common understanding of these more generally used and imprecise terms. Additionally, the need for further research in this area, including on individual variation that arises from genetic and other factors, should be acknowledged (Schmidt and Goodwin, 2013).

Does the Evidence Report Provide Evidence That the Named Gaps Are the Most Critical Presented?

The 13 topic areas addressed by the gaps enumerated in Section VIII of the evidence report are all highly relevant to the development of medical capabilities for exploration-class missions. The steps needed for the resolution of these 13 existing gaps are not articulated nor is the desired end state or requirement clearly stated. The committee also found that the gaps as currently worded may be worded too broadly. For example, the description of gap Med02 says “We do not have the capability to provide a safe and effective pharmacy for exploration missions” (Antonsen et al., 2017, p. 51). This contrasts with the extensive quantitative data provided in the report text on the topic of pharmaceuticals, and focusing on the specific needs in understanding pharmacokinetics and pharmacodynamics in the space environment would be beneficial.

Stating the gaps as such broad generalizations does not seem useful in informing the next steps for HRP. In their current form, the descriptions of the gaps also appear to discount the accumulated experience to

date on health- and medical care–related issues. A reading of the gaps stated in other HRP risk reports should facilitate finding a more actionable formulation of the gaps.

Are There Any Additional Gaps or Aspects to Existing Gaps That Are Not Addressed for This Specific Risk?

The committee suggests that NASA consider adding the following to the list of existing gaps:

• The development of a fundamental health risk matrix for exploration missions, with associated risk mitigation measures directed to key phases of the operations: Earth launch, zero-G, transit, landing G, partial-G at destination, remote launch, zero-G transit, and landing. The risk matrix could include the estimated probability of occurrence of each condition and its mission impact if it occurs. Such a modular matrix could be adapted to mission architecture as needed.
• The development of decision-support principles for making diagnoses of health conditions in space, particularly in settings of long communications latency or lost communications.
• Understanding the relevance of health care delivery models in austere and chaotic environments that face the stark reality of limited inventory, such as refugee camps, the battlefield use of medics, and military models involving prolonged field care.
• The development of effective methods for administering anesthesia (both local and regional block) and for the conducting of emergency surgery. In this regard, a workshop participant noted that one backpack gets most emergency surgery done.
• The development of balanced mitigation strategies for engineering and biomedical risks. Although engineering risk would often appear to trump other risks, there are purely humanitarian reasons to address biomedical risks. In addition, risks accumulate mathematically so that even apparently small risks can become significant.
• The development of standards of care for exploration medicine focused on pragmatic decision making, rather than terrestrial standards of care.

• The development of an atlas of clinical procedures for spaceflight, including definitions and effective methods for teaching these procedures.
• The evaluation of the utility of clinical training models for extended duration missions that employ just-in-time- and simulation-based training, particularly for uncommon conditions.
• The development of training approaches to maintaining proficiency with manual skills (e.g., intravenous insertion), particularly those that are expected to have different methods from those used for terrestrial medical care.
• The development of protocols for treating common injuries, such as fractures, that might enable crewmembers to continue participating in team activities, including the use of a pressure suit if required, thus minimizing the risk to the mission as well as optimizing the health outcome for the individual astronaut.

Does the Evidence Report Address Relevant Interactions Among Risks?

The report addresses in its introductory section the interaction of risks and tradeoffs involved in provisioning limited medical capability for missions affected by long communications latency and an inability to provide medical evacuations. In addition the detailed sections on bone fracture, dust exposure, and renal stone formation address risk interactions for those conditions. Because mission medical capabilities have potential interactions with essentially all of HRP’s health risks other than perhaps the long-term risk of cancer and other degenerative diseases, a comprehensive health risk matrix as suggested above could serve as a concise mechanism for representing all important risk interactions.

What Is the Overall Readability and Quality?

The committee found much of the report to be well written and understandable. However, the writing is uneven and could use tighter editing for grammar and readability, with more limited reliance on acronyms. Furthermore, the committee took note of the reference to the Challenger disaster as a “mishap,” which trivializes the tragedy and appears to imply that it was an unavoidable accident when subsequent analyses found that much could have been done through engineering and through fostering a culture of safety. With respect to both readability and

consistency with other NASA program documents, the committee notes that in 2017 no one refers to human space exploration as “manned spaceflight.”

Is the Breadth of the Cited Literature Sufficient?

Overall, the cited literature in the report is broad and reflective of more recent Shuttle/ISS experience. There is a breadth of NASA technical material from Gemini, Apollo, Skylab, and NASA-Mir missions that is worthy of review in the context of mitigating the health risks of beyond-Earth-orbit missions. Literature that could be reviewed for incorporation into the report includes publications pertaining to critical care, to anesthesia in space based on parabolic flight, to ISS animal research, and to analog environments. Specific additional references that could help inform the quantitative estimation of risk of various health conditions associated with exploration-class missions include Buckey (2006) and Stuster (2010).

Is the Expertise of the Authors Sufficient to Fully Cover the Scope of the Given Risk? Is Input from Additional Disciplines Needed?

The expertise of the current authors appears to match the scope of the report as written. Additional input from those with operational medical care delivery experience, particularly NASA flight surgeons and physician astronauts, could do much to help portray the value—and limits—of real-world experience in formulating the research and development agenda for this area of focus in NASA’s HRP. The Mars expedition task analysis that is currently being conducted by Stuster and colleagues for NASA’s Human Factors & Behavioral Performance Element (under NASA Grant Number NNX15AW34G) has generated a 1,130-item task inventory that could help inform the likelihood and type of injury and illness during expedition-class space missions.

Has the Evidence Report Addressed Previous Recommendations Made by the IOM in the 2008 Letter Report?

The chapter of the 2008 report most closely aligned with the current report is titled “Inability to Adequately Treat an Ill or Injured Crew Member.” The overall assessment of the 2008 committee was that this topic was in “an early stage of development” and that “a detailed list of