Dose Tracker: an iOS app for collection of medication use data from volunteer crewmembers on the International Space Station
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1
Center for Space Medicine, Baylor College of Medicine, United States
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2
JES Tech, United States
Introduction
During space flight, the body undergoes a number of physiological changes that would be expected to result in altered interactions with administered medications, but it is not yet known if, or to what extent, clinically-relevant pharmacology changes occur. The potential for alteration in either pharmacokinetics (PK, how the body handles administered medications) or pharmacodynamics (PD, how administered medications act upon the body) has long been a concern. Potential causes of spaceflight associated PK alterations include cephalad fluid shifting, which could alter absorption of orally-administered drugs and/or distribution of drugs to target tissues. There have been reports of a changes in gastrointestinal transit time (1), calcium absorption (2), and in the amounts of liver enzymes involved in drug metabolism (3-5). Regarding pharmacodynamics, tissue remodeling may alter cell phenotypes and expression of cell membrane receptors that serve as drug targets; it is well-demonstrated that bone (6) and muscle (7) exhibit significant remodeling during spaceflights. PK/PD studies are routine on Earth, but are not very feasible in spaceflight, requiring dozens to hundreds of subjects, and multiple blood draws over the course of 8-16 hours. This observational epidemiological study was a noninvasive attempt toward addressing the paucity of PK/PD evidence by regular direct questioning of crewmember volunteers regarding their user experiences with medications used during missions.
Methods
App development
An examination was made of methods used previously to collect medication usage data. Mission medical records and physician notes only captured data deemed relevant by flight surgeons or other clinical personnel, and did not routinely capture data that would be pertinent to potential PK/PD alterations. Post-flight medical debrief questionnaires could be lengthy, had low response rates and/or missing data (8),and did not include perceived side effects or efficacy.
For this study, a tablet-based questionnaire was designed to provide a streamlined individualized data entry system for the user. Specific questions regarding medication use were asked of each participating crewmember, somewhat different from the questions that physicians ask regarding patient health. These included subject’s perception of drug efficacy (including pain ratings on the Wong-Baker scale for indications involving pain) and questions regarding the occurrence, severity and timing of any side effects.
The data collection process was streamlined with flexible programming that leveraged the limited medication choices aboard, the doses available, typical dosing frequency, and side effects associated with each medication (Figure 1). For chronically-used medications like a daily vitamin, the app permitted subjects to make a single medication usage entry that covered a specific range of dates. The study team requested input on the app from JSC Pharmacy, flight surgeons and crew during development and testing. The app was tested during 4 HERA missions at JSC, which was a very low-fidelity analog for pharmacological purposes since medication use is not typically permitted in this analog.
Implementation
This study was approved by the Institutional Review Boards of Baylor College of Medicine and NASA Johnson Space Center. Approximately one year prior to a planned ISS mission, astronaut subjects were briefed regarding the study and were consented to participate. Subjects were trained on app usage and were asked to record all medication usage, including prescription, over-the-counter, and nutritional supplements. Pre-flight or post-flight, each participating crewmember recorded their medication usage for a duration equivalent to their on-orbit mission, so that their ground medication usage frequencies, doses, and perceptions could be compared to those recorded during their spaceflight mission.
Coded (de-identified) data were delivered weekly to a secure server for analysis by study investigators. The study was written and approved for a total of 24 subjects, in order to yield at least 6 subjects using common medications. One aim of the study was to acquire sufficient in-flight medication usage data to provide the necessary variance and effect-size information required to properly power future studies when they are needed.
Results
Seven subjects consented to participate during the abbreviated study period. One subject dropped before the beginning of data collection. Five subjects completed both flight and ground data collection; one additional subject completed only data collection during flight.
A total of 5766 records of medication use were collected. There were 20.63 ± 8.47 entries per subject per flight week; 15.62 ± 4.58 per ground week (mean ± SEM).
Notably, the app collected 49 reports of no medication use in a given week of data collection, providing positive confirmation that a crewmember was not using medications. Medical records had no such indication, forcing researchers to instead rely on the (possibly incorrect) assumption that no recorded data means no medication usage.
Subjects also provided feedback and usability of the app, which was mixed. A number of lessons learned have been captured regarding the need for multiple secure login steps, time zone issues on Earth, issues with the Apple iOS operating system, and NASA processes for software updates and data transfers. Procedures to ensure subject privacy were cited as the reason for multiple complaints. One subject requested that data be shared with their flight surgeon. Using the app to provide information for medical care was not planned, and required special approval from the JSC IRB to arrange. Data sharing between the research study and the clinic was successfully managed for the mission duration and indicates a level of clinical interest in the data collected by the study.
Discussion
The study demonstrated a significant increase in the amount of medication usage information being collected. Self-reports of medication use collected by the app were higher than found in medical records, by more than an order of magnitude (9). This is now being used as rationale to update medical operations requirements for the collection of this type of information on the ISS.
The funding agency, NASA Human Research Program, elected to end this study well before its planned 24 subjects could be completed. With only 5 subjects, it is not possible to achieve the aims of collecting data regarding inflight PK or PD changes. It is hoped that the lessons learned will prove useful for future attempts to record astronaut medication use in a timely and complete fashion.
Figure Legend
Figure 1. Screen shot of Dose Tracker main data entry page. The current date and time were used as defaults, but could be altered by the user to dates and times in the past. Designed to leverage the known contents of the ISS medical kit, the app showed likely choices of medications for each user-entered complaint, and likely side effects for each medication. Users could also freely type in entries.
Acknowledgements
The authors wish to thank Drs. Scott M. Smith, Michael Barratt, Serena Aunon-Chancellor, Jennifer Law and Jack Stuster for helpful discussions, Mr. Jeffrey Reilly for software development, and the astronaut participants.
References
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2. Caillot-Augusseau A, Vico L, Heer M, Voroviev D, Souberbielle JC, Zitterman A, et al. Space flight is associated with rapid decreases of undercarboxylated osteocalcin and increases of markers of bone resorption without changes in their circadian variation: observations in two cosmonauts. Clin Chem. 2000;46(8 Pt 1):1136-43.
3. Merrill AH, Jr., Hoel M, Wang E, Mullins RE, Hargrove JL, Jones DP, et al. Altered carbohydrate, lipid, and xenobiotic metabolism by liver from rats flown on Cosmos 1887. FASEB J. 1990;4(1):95-100.
4. Merrill AH, Jr., Wang E, Jones DP, Hargrove JL. Hepatic function in rats after spaceflight: effects on lipids, glycogen, and enzymes. Am J Physiol. 1987;252(2 Pt 2):R222-6.
5. Merrill AH, Jr., Wang E, LaRocque R, Mullins RE, Morgan ET, Hargrove JL, et al. Differences in glycogen, lipids, and enzymes in livers from rats flown on COSMOS 2044. J Appl Physiol. 1992;73(2 Suppl):142S-7S.
6. Vico L, Collet P, Guignandon A, Lafage-Proust MH, Thomas T, Rehaillia M, et al. Effects of long-term microgravity exposure on cancellous and cortical weight-bearing bones of cosmonauts. Lancet. 2000;355(9215):1607-11.
7. Szilagyi T, Szoor A, Takacs O, Rapcsak M, Oganov VS, Skuratova SA, et al. Study of contractile properties and composition of myofibrillar proteins of skeletal muscles in the Cosmos-1129 experiment. Physiologist. 1980;23(Suppl 6):S67-70.
8. Putcha L. Data mining - Pharmacotherapeutics of Space Motion Sickness. 2009.
9. Wotring VE. Medication use by U.S. crewmembers on the International Space Station. FASEB J. 2015;29(11):4417-23.
Keywords:
spaceflight,
microgravity,
Pharmacy,
Pharmacology,
pharmacokinetics,
Pharmacodynamics
Conference:
39th ISGP Meeting & ESA Life Sciences Meeting, Noordwijk, Netherlands, 18 Jun - 22 Jun, 2018.
Presentation Type:
Extended abstract
Topic:
Astronaut health
Citation:
Wotring
V and
Smith
L
(2019). Dose Tracker: an iOS app for collection of medication use data from volunteer crewmembers on the International Space Station.
Front. Physiol.
Conference Abstract:
39th ISGP Meeting & ESA Life Sciences Meeting.
doi: 10.3389/conf.fphys.2018.26.00047
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Received:
02 Dec 2018;
Published Online:
16 Jan 2019.
*
Correspondence:
Dr. Virginia Wotring, Center for Space Medicine, Baylor College of Medicine, Houston, United States, vwotring@gmail.com