design effective interventions to alleviate the consequences of delayed or absent mail-order prescriptions.
We show that the use of mail-order medications has become more prevalent among U.S. adults over the past two decades, with an increase from 13.5 million adults in 1996 to 25.9 million adults in 2018.
Given that USPS delivers 55% of all mail-order medications, a considerable proportion of mail-order pharmacy consumers could experience a delay or non-delivery of their medications. The use of mailorder medications is most common among older adults, disabled and chronically ill persons, and military-insured beneficiaries, who may have limited access to a local drugstore due to their morbidities or disability. In addition, we document a variety of medications frequently delivered by mail -ranging from those for which missing several doses does not result in immediate adverse health consequences (e.g. statins), to those for which missing a dose could be detrimental to the patient's health (e.g. insulin).
Our findings highlight that any disruption in the postal service could lead to important medical complications among a considerable proportion of the vulnerable U.S. population. The potential health consequences of a widespread national slowdown in mail delivery should be considered when weighing options to reverse recent changes at the USPS.
Since 2006, the United States Postal Services (USPS) has faced $83·1 billion in cumulative losses, 1 mainly due to declining mail volumes and a mandate requiring the agency to prefund its employee benefits. 2 In May 2020, USPS ordered aggressive cost-cutting measures, including slashing overtime delivery trips, sorting machines, and other expenses required to ensure punctual mail delivery. 3 The National Association of Letter Carriers recommended that the U.S. Congress should provide at least $25 billion in direct financial aid to help strengthen the USPS and reverse recent changes. 2 However, the U.S. President has recently threatened to veto any congressional postal bills due to concerns about voter fraud related to mail-in ballots. 4 Studies have consistently found that mail-order medications are associated with reduced healthcare costs and better health outcomes as a result of improvements in medication adherence. [5] [6] [7] However, in a weekly survey conducted in August 2020, one in four mail-order prescription users reported experiencing a delay or non-delivery of their medications during the preceding week. 8, 9 Given anecdotal reports that many patients have switched to mail-order prescriptions since the start of the SARS-CoV-2 epidemic to prevent potential exposure to infection in stores, 10 demand for mail-order medications -and thus reliance on the USPS mail delivery system -has likely risen over the past months. Delay of critical prescriptions may force patients to visit their local pharmacy, potentially putting them at risk of contracting the virus. Picking up medications from a local drugstore may also increase patients' copay because many insurance companies cover a higher proportion of the cost when a medication is delivered by mail. 7 Moreover, many medications are unavailable at the local drugstore because they are a controlled substance or because they are in shortage due to the SARS-CoV-2 epidemic. 11 . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint
The copyright holder for this this version posted September 23, 2020. . https://doi.org /10.1101 /10. /2020 Efforts aimed at addressing the health and economic effects of delayed medication delivery require an understanding of the national prevalence of mail-order prescription and the population groups who will likely be most affected by these postal delays. Several studies have estimated the prevalence of mailorder prescription, but they are either outdated, 12, 13 unrepresentative of the U.S. population, 13-15 or unable to assess variation in prevalence and time trends by socio-demographic and health characteristics. 14, 16 This study uses nationally representative data to determine: (a) the prevalence of mail-order prescription from 1996 to 2018 among U.S. adults, (b) how the prevalence and time trends vary by sociodemographic characteristics, physical access to a usual place for medical care, and health characteristics, and (c) which medications are most likely to be delivered by mail.
The Medical Expenditure Panel Survey (MEPS) is a nationally representative survey of the civilian noninstitutionalized U.S. population drawn from a subsample of households that responded to the prior year's National Health Interview Survey (NHIS). 17 The NHIS is a complex, multistage probability survey conducted in each state and the District of Columbia. In the first stage, a random sample of primary sampling units (PSUs) was selected with the probability of selection being proportionate to a PSU's population size as estimated by population projections from the U.S. Census Bureau. The second stage consisted of a probability sample of geographic area segments within each PSU. These segments were subsequently divided into clusters, each of which included approximately four to nine housing units. Racial/ethnic minority households were oversampled at a rate of 2:1. Each year, the MEPS randomly selected three-eighths of the households that responded in the prior year's NHIS. The MEPS's . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint
The copyright holder for this this version posted September 23, 2020. . https://doi.org/10.1101/2020.09.22.20199505 doi: medRxiv preprint response rate, after accounting for non-response in the NHIS, ranged from 78% in 1996 to 46·8% in 2018. 18 MEPS participants enter the survey each year as members of a unique panel. They are interviewed in five sequential rounds spanning two years. Data are organized as annual files, each of which includes members from two unique panels. Analyses were based on adults aged 18 years and older in all available MEPS surveys (1996 to 2018) (N = 507,629). After excluding 7,412 persons with incomplete data on mail-order prescription, the final sample was 500,217. This study is exempt from Institutional Review Board approval because MEPS data are in the public domain.
In each survey round, respondents reported the name(s) of all prescribed medication(s) that they filled and refilled (whether through the mail or not) during the reference period. The reference periods vary across households, but they typically cover five months on average. Each refill was treated as a single medication record. From 1996 to 2018, approximately 70-80% of respondents signed the permission forms for MEPS to contact their pharmacies, 77% of which agreed to provide information on respondents' reported medications. 18, 19 All medications were linked to a proprietary database -Lexicon Plus, Cerner Multum -that contains information on all prescription medications available in the U.S.
market. The quality of prescription data has been validated elsewhere. 20 Participants were asked for the type of pharmacy from which each medication was purchased, with the options included mail-order pharmacies; pharmacies located in another store such as a grocery or department store; pharmacies located in an HMO, clinic, or hospital; drug stores that are not located within another facility; or on-line pharmacies. Mail-order prescriptions were defined as those obtained from either a mail-order pharmacy or online store.
Ascertaining socio-demographic characteristics, physical access to a pharmacy, and health status . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint
The copyright holder for this this version posted September 23, 2020. . https://doi.org/10.1101/2020.09.22.20199505 doi: medRxiv preprint MEPS asked participants about the following socio-demographic characteristics: age (categorized in this analysis as 18-44 years, 45-64 years, and 65 years and older), sex, race/ethnicity (non-Hispanic white, non-Hispanic black, non-Hispanic Asian, non-Hispanic others, or Hispanic), education (less than high school, high school graduate, and college graduate), marital status (married, divorced/widowed/separated, and never-married), household poverty level (less than 200%, 200-399%, and 400% or higher of the federal poverty threshold), region of residence (Northeast, Midwest, South, and West), and health insurance coverage (Medicare beneficiaries, Medicaid or public insurance only, military insurance only, private insurance only, and uninsured). To ascertain physical access to the usual place for medical care, respondents were asked for the amount of time it took them to travel to their usual place of medical care, with the response options being less than 15 minutes, 15-30 minutes, 31-60 minutes, and more than 60 minutes. To ascertain health status, participants were asked to rate their general health, with excellent, very good, good, fair, or poor being the response options. In addition, participants were asked whether pain interfered with their normal work last month (none or a bit of the time, and some, most, or all of the time). Limitations in daily activities or routine functions ("any limitation" hereafter) were defined as whether a participant reported any instrumental activities of daily living (IADL) limitation, activities of daily living (ADL) limitation, functional limitation, activity limitation, hearing impairment, or vision impairment. The number of chronic conditions (none, one, two, and three or more) was based on self-report diagnoses of medical conditions. Each condition was recorded as verbatim text then coded to ICD-9 codes. We defined the following conditions as chronic:
hypertension, congestive heart failure, coronary artery disease, cardiac arrhythmias, hyperlipidemia, stroke, arthritis, asthma, cancer, chronic kidney disease, chronic obstructive pulmonary disease, dementia, diabetes, hepatitis, human immunodeficiency virus (HIV), and osteoporosis. 21
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We estimated the prevalence of using any mail-order prescription and the mean number of mail-order prescriptions in a calendar year using sampling weights that accounted for the survey design. The variance of these estimates was calculated using the Taylor series linearization method. Both estimates were age-standardized to the population age distribution of the U.S. in 2000 as published by the U.S. National Census Bureau (Appendix Figure 1 ). 22 All estimates were stratified by socio-demographic characteristics, physical access to the usual place for medical care, and health status. We reported the prevalence of mail-order prescription use among the general adult population for the 25 medications that constituted the largest proportion of all medications delivered by mail. In addition, we reported the prevalence of use for the 25 medications that were most commonly delivered by mail among the users of these medications, conditional on having at least 500 users in the pooled 1996-2018 data to allow for reasonably precise estimates.
All analyses were conducted using Stata version 13.0.
The funder had no role in study design, data collection, data analysis, data interpretation, or writing of the article. The first author and corresponding author had full access to the data and had final responsibility for the decision to submit for publication.
Sample characteristics and prevalence of mail-order prescription use: Table 1 presents descriptive statistics for socio-demographic and health characteristics of the full sample and by the use of mail-order prescription. Overall, 9·8% (95% CI, 9·5%-10·0%) of adults used at least one mail-order prescription in a year. Among these individuals, each user filled a mean of 19·4 (95% CI, . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint 1 1 19·2-19·6) mail-order prescriptions per year. Compared to nonusers, mail-order prescription users were more likely to be older, female, non-Hispanic white, college educated, married, high-income, reporting poor or fair health, experiencing pain interference with their normal work, having any limitation, reporting multiple chronic conditions, Medicare beneficiaries, and having a usual place for medical care.
The prevalence of mail-order prescription use varied markedly between population groups ( Figure 1 ).
Among adults aged 65 and older who reported having three or more chronic conditions, 33% of non-Hispanic whites (Panel A), 37% of college graduates (Panel B), 35% of married adults (Panel C), and 39% of high-income adults (Panel D) used mail-order prescription. More generally, the prevalence of mail-order prescription use was particularly high among older adults (23·1% [95% CI, 22·5%-23·8%]), 25·3%-26·9%]), Medicare beneficiaries (21·8% [95% CI, 21·3%-22·4%]), and adults whose travel time to their usual place for medical care was more than 60 minutes (14·7% [95% CI, 13·1%-16·3%]) (Appendix Table 1 ).
The prevalence of mail-order prescription use increased from 6·9% (95% CI, 6·4%-7·5%) in 1996 to 11·4% (95% CI, 10·6%-12·1%) in 2005 (Appendix Figure 1 , Panel A), stagnated between 2006 and 2011, then declined after 2011, with the prevalence in 2018 being 10·3% (95% CI, 9·7%-10·9%). Each user purchased a mean of 10·7 (95% CI, 9·8-11·7) mail-order prescriptions in 1996, which increased to . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. In 2018, differences in the prevalence of mail-order prescription use between income groups were comparatively small among high-income (12·6 % [95% CI, 11·6%-13·6%]), middle-income (9·5% [95% CI, 8·5%-10·5%]), and low-income adults (7·3% [95% CI, 6·4%-8·2%]).
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The prevalence of mail-order prescription use among other subpopulations generally increased during the first ten years of the study period and then declined. In Appendix Figure Population groups with a consistently low prevalence of mail-order prescription use throughout the study period included adults with less than a high school education (Appendix Figure 2 ); as well as adults without chronic conditions, Medicaid or publicly insured adults, uninsured adults, and adults without a usual place for medical care (Appendix Figure 3 ). Time trends in the prevalence of mail-order prescription use by limitation and pain interference are shown in Appendix Figure 3 , and by type of limitation in Appendix Figure 4 .
Among the general U.S. adult population, mail-order prescriptions were commonly filled for analgesics (Table 2 and Appendix Table 2 ). Medications most commonly purchased by mail among their users are listed in Table 3 and Appendix Table 3 . Adults who use antihyperlipidemic medications were most likely to obtain these by a mail-order prescription, with between 32·5% to 35·9% of those using ezetimibe, ezetimibe-simvastatin, and niacin receiving these medications in the mail. Other commonly mailed . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint
The copyright holder for this this version posted September 23, 2020. . https://doi.org/10.1101/2020.09.22.20199505 doi: medRxiv preprint medications -all of which have a prevalence of mail-order prescription use of about one-third among their users -included estrogen, cardiovascular agents (e.g. hydrochlorothiazide-irbesartan, nadolol, and irbesartan), bone resorption inhibitors (e.g. ibandronate, alendronate, and risedronate), and topical estradiol.
From 1996 to 2018, the use of any mail-order prescription grew from 6·9% to 10·3%, an increase of 48·6% relative to the baseline. Among users, the number of mail-order medications increased by almost two-fold between 1996 and 2018. Mail-order prescriptions were most commonly used among older adults, adults of high socioeconomic status, disabled and chronically ill persons, and military-insured beneficiaries. While mail-order prescription use was more common among high-income adults than middle-and low-income adults, the differences in mail-order prescription use between income groups have narrowed in recent years. Medications most commonly delivered by mail included those for which missing several doses does not result in immediate adverse health consequences (e.g. statins), but also those for which missing a dose could be detrimental to the patient's health (e.g. insulin), produce considerable discomfort (e.g. analgesics), have negative consequences for public health (e.g. antibiotics for which delayed or lacking mail-order prescriptions may result in incomplete antibiotic courses and, thus, an increased risk of antibiotic resistance), or that could be critical in sudden deteriorations of a chronic condition (e.g. albuterol).
To our knowledge, this study is the first to use a nationally representative survey of U.S. adults to assess the prevalence of mail-order prescription over the past two decades. Ma and Wang have previously used MEPS to estimate the prevalence of mail-order prescription use but they only used the 2012 wave of the survey and excluded respondents who entirely filled their prescriptions at Health Maintenance . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint
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Organizations, clinics, or hospitals throughout the year. 12 Other studies have used non-representative samples, such as online surveys or studies that only sampled a particular population subgroup. 13, 15, 23 Our study found that the use of mail-order prescription has slowed down among the adult population, This study identified several subpopulations that rely heavily on mail-order prescriptions. It is likely that a deterioration in the availability or reliability of mail-order prescriptions from cost-cutting measures at the USPS will affect these population groups the most. In particular, adults in the poorest health will likely be hit hardest by USPS cost-cutting measures because they are physically least able to travel to the pharmacy to obtain their medications and our analysis showed them to be most probable to be using mail-order prescriptions. Importantly, it is also these adults who will be at the highest risk of a fatal disease course if they acquire a SARS-CoV-2 infection while in, or traveling to, the pharmacy. 26 Given that we found that a wide variety of prescribed medications are commonly delivered through the mail, . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) preprint
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the immediate consequences of delayed or absent mail-order prescriptions could range from poorer adherence to preventive medications to an increased incidence of health emergencies, such as diabetic ketoacidosis or acute exacerbations of asthma.
The social equity implications of reduced availability and reliability of mail-order prescriptions are likely to be profound. While we found that high-income adults still use mail-order prescription medications more heavily than middle-and low-income adults, the differences in use between income groups have narrowed considerably over recent years. Indeed, a simple linear extrapolation of the trends since 2014 suggests that both middle-and low-income adults may already be having a higher prevalence of mail-order prescription use in 2020 than high-income adults. Regardless, it is likely that, on average, individuals with lower income and less education will find it more difficult to change from receiving medications through the USPS to receiving them through another postal carrier or picking up medications in person. The potential reasons are numerous, including a lower ability to bear additional costs from such a change, less flexible employment situations to allow for time to pick up medications, and lower health literacy. 7, 27 While our study is unique in its use of a nationally representative repeated cross-sectional sample of adults for each year spanning more than two decades, it faces some limitations. First, we were not able to determine the prevalence of using mail-order pharmacy for over-the-counter medications because MEPS only collected data on prescription medications. Second, our measure of using mail-order prescriptions was based on self-report and may, thus, be affected by recall bias. However, among those who reported using any prescriptions, the MEPS team was able to contact the pharmacy of over half of participants to verify their answers. Third, while the response rate of the NHIS and MEPS is high compared to other health surveys in the U.S., 28,29 it is possible that adults who were selected for the . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
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survey but were not reached or declined to participate had a systematically different prevalence of mailorder prescription use than MEPS participants. The sampling weights in the MEPS accounted for nonresponse using participants' measured socio-demographic characteristics. Finally, we were unable to examine the prevalence of mail-order prescription delivered by USPS because MEPS did not collect data on the service carrier. It has been estimated that USPS delivers 55 percent of the nation's medications. 30
The use of mail-order prescription is common among U.S. adults, particularly among those in poorer health, and has increased substantially since 1996. Our analysis highlights that any disruption in the postal service could lead to important medical complications among a considerable proportion of the U.S. population. These health consequences should be taken into account when weighing operational and funding changes to the USPS.
DD and PG conceived and designed the study. DD processed the data, conducted the analyses, and visualized the data. DD and PG interpreted the results. Both authors wrote the first draft of the manuscript, critically revised the article, and approved the final version.
We declare no competing interests.
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The copyright holder for this this version posted September 23, 2020. ] a: Weighted estimates using sampling weight. b: Estimates may not add up to 100% due to rounding error. c: Based on 40,131 respondents who reported using at least one mail-order prescription in a calendar year. d: Excludes 3756 respondents whose educational attainment was not collected. e: Excludes 15 respondents whose marital status was not collected. f: Households were classified into three categories based on their total income and household composition: low-income (less than 200% of the federal poverty threshold), middle-income (200-399%), and high-income (>= 400%). g: Excludes 4 respondents whose region of residence was not collected. h: Excludes 108893 respondents whose health status was not collected. MEPS started collecting this variable in 2000. Respondents interviewed before 2000 were removed for this particular variable. i: Excludes 108628 respondents whose information on pain interference was not collected. MEPS started collecting this variable in 2000. Respondents interviewed before 2000 were removed for this particular variable. j: Excludes 5471 respondents whose limitation status was not collected. The variable was constructed based on whether a person has any instrumental activities of daily living (IADL) limitations, activities of daily living (ADL) limitations, functional limitations, activity limitations, hearing impairment, or vision impairment. k: Excludes 68685 respondents whose information on chronic conditions was not collected. In 2016, MEPS started using the International Classification of Diseases 10 (ICD-10) instead of ICD-9. As such, the medical classifications of conditions in 2016 are still under review. Respondents interviewed after 2015 were removed for this particular variable. The following conditions are classified as chronic: hypertension, congestive heart failure, coronary artery disease, cardiac arrhythmias, hyperlipidemia, stroke, arthritis, asthma, cancer, chronic kidney disease, chronic obstructive pulmonary disease, dementia (Alzheimer's and other senile dementias), diabetes, hepatitis, human immunodeficiency virus (HIV), and osteoporosis. l: Excludes 114,774 respondents whose travel time to the usual place of medical care was not collected. MEPS started collecting this variable in 2002. Respondents interviewed before 2002 were removed for this particular variable. Abbreviation: CI, confidence interval.
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Note: Prevalence of mail-order prescription use is presented in each cell. a: The numerator was the number of adult MEPS participants who obtained a mail-order prescription for the medication, and the denominator was the number of adult MEPS participants who have been prescribed the medication. Abbreviation: CI, confidence interval.
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The copyright holder for this this version posted September 23, 2020. . b: Excludes 3756 respondents whose educational attainment was not collected. c: Excludes 15 respondents whose marital status was not collected. d: Households were classified into three categories based on their total income and household composition: lowincome (less than 200% of the federal poverty threshold), middle-income (200-399%), and high-income (>= 400%). e: Excludes 4 respondents whose region of residence was not collected. f: Excludes 108893 respondents whose health status was not collected. MEPS started collecting this variable in 2000. Respondents interviewed before 2000 were removed for this particular variable. g: Excludes 108628 respondents whose information on pain interference was not collected. MEPS started collecting this variable in 2000. Respondents interviewed before 2000 were removed for this particular variable. h: Excludes 5471 respondents whose limitation status was not collected. The variable was constructed based on whether a person has any instrumental activities of daily living (IADL) limitations, activities of daily living (ADL) limitations, functional limitations, activity limitations, hearing impairment, or vision impairment. i: Excludes 68685 respondents whose information on chronic conditions was not collected. In 2016, MEPS started using the International Classification of Diseases 10 (ICD-10) instead of ICD-9. As such, the medical classifications of conditions in 2016 are still under review. Respondents interviewed after 2015 were removed for this particular variable. The following conditions are classified as chronic: hypertension, congestive heart failure, coronary artery disease, cardiac arrhythmias, hyperlipidemia, stroke, arthritis, asthma, cancer, chronic kidney disease, chronic obstructive pulmonary disease, dementia (Alzheimer's and other senile dementias), diabetes, hepatitis, human immunodeficiency virus (HIV), and osteoporosis. j: Excludes 114,774 respondents whose travel time to the usual place of medical care was not collected. MEPS started collecting this variable in 2002. Respondents interviewed before 2002 were removed for this particular variable. Abbreviation: CI, confidence interval.
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Note: All estimates were not age-standardized.
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Note: All estimates were not age-standardized.
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