These findings suggest that there is a high economic cost associated with ME/CFS for patients, their families, and for society as a whole. This study has provided a conservative estimate of the direct economic impact of ME/CFS, with a mean annual cost of $2,342 to $8,675 per patient. When extrapolated to the U.S., the direct cost to the American health care system is estimated to be from $1, 957,912,000 to 7,252,000,000.
In other words, the total annual direct estimated costs for the tertiary sample were nearly three times the cost of the community sample.
It is at least possible that these differences might have been due to the differing characteristics of the sample. In study 1, the majority of participants with ME/CFS were minorities, whereas in study 2, 90% were Caucasian. There were also differences in the educational attainment between the two samples. Among those with ME/CFS in study 1, only 48% had at least standard college degree, whereas among those is study 2, 71% had this level of educational attainment. Finally, the majority of those in study 1 had never been diagnosed with ME/CFS, whereas all of those participants in study 2 had this diagnosis. Very possibly, those participants with ME/CFS in study 1 had less resources to devote to medical care, and the majority did not even know that had this illness. In contrast, all of those in study 2 had a ME/CFS diagnosis, and they had possibly had more resources to invest in the medical diagnosis and treatment of this illness. These data suggest that the economic cost of ME/CFS will vary between those in community-based samples who might not have been diagnosed and those in tertiary clinics, who might have a diagnosis and more resources, and these differences may influence the societal cost of ME/CFS.
These economic losses can have a substantial long-term impact on ME/CFS patients' standard of living and quality of life. With high unemployment rates among ME/CFS patients, the direct cost of medical services could become even more problematic to individuals and families due to a loss of health insurance benefits and thus, increases in out-of-pocket medical expenses. Our estimate of the direct cost of medical expenses was $2,342 to $8,675 per ME/CFS patient. This estimate is not directly comparable to previous estimates of the direct cost of ME/CFS due to different sampling strategies. Bombardier and Buchwald  estimated an average annual medical expenditure of $1,031 per ME/CFS patient. Estimates from Lloyd and Pender  and McCrone et al.  used samples from Australia and the U.K. respectively, and due to different health care systems and prevalence rates, are not directly comparable with the current estimate. In addition, these studies had a number of other differences that might account for the varying cost estimates (e.g., use of different diagnostic criteria and definitions; differential levels of severity of ME/CFS symptoms and other comorbidities).
In addition to the direct medical costs imposed on individuals and society, there is also a substantial economic costs related to lost productivity. Participants with ME/CFS were receiving more disability benefits, and were more likely to be unemployed or working part-time than their control counterparts. Indirect costs to the individual and society can be estimated according to a study conducted by Reynolds et al., . According to their study, approximately one third of patients with ME/CFS, who in other circumstances would have participated in the work force, stopped working and for those who continued working, their income was cut by a third. This change in employment status represented an estimated annual loss of $20,000.
Although our data did not include salary variables and indirect costs could only be examined in terms of work status change and increased disability, we could apply the Reynolds  figure ($20,000) to our sample. For study 1, using estimates from Reynolds et al. , we could estimate that the annual indirect cost to society to be $16,720,000,000 (836,000 × $20,000) or almost $17 billion. Together the total indirect and direct costs to society could be estimated to be $18,677,912,000, or over 18 and a half billion dollars. For study 2, the estimated total annual indirect cost to society is 836,000 × $20,000 = $16,720,000,000. Therefore, in study 2, together the total indirect and direct costs to society equals $23,972,300,000 or close to 24 billion dollars. For studies 1 and 2, the total direct and indirect costs due to ME/CFS were estimated to range from 17 to 24 billion dollars.
When interpreting the findings from the current study, some limitations should be considered. First, our study relied on archival data, and therefore did not include some information that would have been helpful in estimating the economic impact. For example, we did not have an estimate of salary or a measure of the actual number of work hours lost. According to McCrone et al. , an important variable in estimating the indirect cost is the role of informal care providers. Informal care providers refer to friends or relatives that help care for the patient without remuneration, but still incur an opportunity cost. Our archival data did not include variables to estimate these types of financial losses. Therefore, we could not calculate costs due to lost productivity, and estimating a specific indirect cost was impossible. Another limitation to the archival data is that participants in the community based sample provided their medical records and completed the self-report questionnaires between 1995 and 1997. Participants infrequently listed alternative medications (herbs or supplements) or treatments (acupuncture) that are more commonly used now, but likely were not frequently used 10 years ago. Participant medical record information also did not include information about hospital stays or ambulatory use. Therefore, our estimates of the direct costs of ME/CFS are likely an underestimate because they do not include these types of service use.
In addition, current medication usage information relied on participant recall of service use, and therefore may not be accurate. However, corroboration of participant medication use was obtained by the examining physician for more than three quarters of the participants in Study 1. Also, other means of data collection besides self-report data were analyzed. The use of medical records likely provided an accurate indication of number of office visits and medical test usage. However, medical records were not available for participants in Study 2. These limitations should be addressed in future research. Ideally, estimates of the economic impact of ME/CFS should include estimates of both direct and indirect costs.
This study suggests that the direct costs of this illness are incurred variously, both by the individual patient and by society. For the community group, the prices of prescriptions and medical services and tests are calculated, but we were not able to determine what portion was covered by insurance and what part was paid out-of pocket. Furthermore, comparison to the control group shows that while the ME/CFS group spends more the total annual direct costs (the mean sum of medication, medical test, and medical office visit costs; $2,342 versus $1,133), this difference only approached significance at the .06 level. More research is clearly needed to be able to answer whether health insurance premiums are more costly on average to those with ME/CFS. It is certainly possible that the direct costs to individuals, primarily deductibles, might be less than estimated. It is also possible that there might be added costs of this illness to the medical industry, but more information is needed concerning retail prices-per-unit in order to calculate industry costs.
In conclusion, Jason et al.  estimates that more than 800,000 adults in the United States have ME/CFS. This figure combined with cost information reported in the current study suggests that ME/CFS has substantial economic costs, whether one uses samples recruited from the community or from a tertiary care clinic. These cost estimates in combination with high prevalence rates are some of the reasons that more research into the cause, effective diagnosis, and treatment are necessary.