
3.6.5.1 Abom

Total Number of Cases that do not Result in Death
We obtained the number of cases per year from the literature on acute otitis media. As ABOM is generally treated in the ambulatory care setting, we, like many other studies, considered it to be exclusively an outpatient disease and therefore used counts of outpatient visits to estimate the number of episodes per year (see, for example, Huang, et al., 2011). The primary sources used by many researchers to obtain information on acute otitis media visits are the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS), which are the only surveys of U.S. outpatient settings that collect drug prescribing information and allow for calculation of unbiased national estimates (Coco, Horst, & Gambler, 2009; Huang, et al., 2011).
To obtain an estimate of the number of cases per year, we used the information contained in Appendix A of the paper by Huang, et al. (2011) on healthcare utilization and the cost of pneumococcal disease. This study uses data from NAMCS/NHAMCS, to report by age group, the total number of outpatient visits for acute otitis media in which antibacterial drugs was prescribed. Based on information gathered from expert panels and other papers, Huang, et al. (2011) also include estimates of how often typical resolution of the disease occurs (as opposed to delayed resolution), the number of followup visits/visits per episode, and the frequency of overdiagnosis. Our first step in calculating the number of episodes per year was to determine the average number of outpatient visits per episode. To do this, we multiplied the probabilities associated with typical and delayed resolution by the number of visits associated with each possibility and arrived at approximately 1.2 visits per episode. Next, we adjusted the number of visits per year by subtracting the estimated proportion of visits that were overdiagnoses, and divided the resulting figures (broken down by age group) by the number of visits per episode, 1.2, to arrive at numbers of episodes per year by age group.
Across all age groups, we found there to be 12.6 million acute otitis media episodes for which antibacterial drugs were prescribed for the year 2004. Our finding is also consistent with the authors’ statements that there were 1.5 million cases of acute otitis media due to pneumococcus, and 12 percent of acute otitis media cases are due to pneumococcus (1.5 million/0.12 = 12.5 million total cases of acute otitis media). Using population estimates by age from the U.S. Census Bureau, we converted the total number of episodes by age group to rates and applied those rates to 2011 population figures to obtain a total number of cases for the year 2011, which we estimated to be 13.2 million. Since there are no deaths associated with ABOM (see discussion below), this is equivalent to the total number of cases that do not result in death.
QALYs Lost per Case
In estimating lost QALYs due to ABOM, we considered one possibility: the patient is ill for a defined period of time and then returns to full health. For more severe conditions, it would be appropriate to also consider the possibility of the patient dying; however, ABOM is not associated with significant mortality, and deaths are therefore unaddressed in the literature (see, for example, Huang, et al., 2011). We also consulted the Compressed Mortality File from the Centers for Disease Control and Prevention and the National Center for Health Statistics and found that the number of deaths associated with various types of acute otitis media were either zero or so small that they were labeled “unreliable.” Therefore, we do not consider the possibility of death in our calculations of QALYs or other social cost estimations for ABOM.
Assuming that all patients eventually recover from ABOM, we considered two possible scenarios: 1) the patient with ABOM is treated, and the initial treatment is successful, and 2) the patient with ABOM is treated, and the initial treatment is unsuccessful, delaying recovery. In the Tufts database, we located a paper that provided numbers of days spent in each stage of the illness/treatment, as well as associated QALY weights (Coco, 2007). This paper evaluated the patient condition over a standard of 30 days. Successful treatment resulted in the patient experiencing acute symptoms for 2.7 days, followed by 27 days of recuperation. Patients whose initial treatment was unsuccessful experienced the same acute symptoms for 2.7 days, followed by another 7 days when the patient would be even sicker; this leaves a 20 day recuperation period. The lost QALY calculations for both possibilities are shown below in Table 17.
According to the ABOM clinical practice guidelines, initial antibacterial drug therapy leads to symptomatic relief at 2 to 3 days in 91 percent of cases; therefore, we weighted success and failure possibilities at .91 and .09, respectively, to arrive at a weighted average of 0.00493 lost QALYs per ABOM episode (American Academy of Pediatrics and American Academy of Family Physicians, Subcommittee on Management of Acute Otitis Media, 2004).
Table 17: QALY Calculations for Acute Bacterial Otitis Media (ABOM)
Scenario Days of ABOM Days of Treatment Success Days of Treatment Failure Initial Treatment Success (3) QALY weight: 0.79
2.7 daysQALY weight: 0.96
27 daysN/A Initial Treatment Failure (4) QALY weight: 0.79
2.7 daysQALY weight: 0.96
20 daysQALY weight: 0.72
7 daysSource: Coco, CostEffectiveness Analysis of Treatment Options for Acute Otitis Media, 2007.
Total QALYs Lost due to Morbidity
Given that lost QALYs per ABOM case is 0.00493 and the total number of ABOM cases in the US is around 13.2 million, we computed the total annual QALYs lost due to ABOM morbidity to be around 65,000 (= 0.00493 × 13.2 million) in the US.
Morbidity Cost
To calculate VSLYbased illness costs (for patients who do not die, which we assume to be all ABOM patients), we first calculated an average VSLY weighted by ABOM incidence by age group in 2011. This weighted average VSLY is roughly $228,000, which is then multiplied by the average lost QALYs per patient (0.00493) to arrive at $1,124 per patient which yields a total morbidity cost of $14.8 billion.


3.6.5.2 Absssi

Total Number of Cases that do not Result in Death
The total number of cases per year was obtained from the literature on skin and skin structure infections. Using data from the Healthcare Cost and Utilization Project National Inpatient Sample (HCUP NIS) for the 5year period from 2000 to 2004, Edelsberg, et al. (2009) estimated the total number of hospital admissions for SSTIs to be 869,777 in 2004. The authors also provided estimates broken down by type of skin infection, allowing us to exclude chronic ulcers and infections, gangrene, necrotizing fasciitis, decubitus ulcer infections, diabetic foot infections, and certain healthcareassociated infections (as specified in the FDA guidance for ABSSSIs) and arrive at an estimated 678,956 hospital admissions for ABSSSIs, or approximately 231.9 per 100,000 population. Applied to the 2011 U.S. population, this rate is equivalent to an estimated 726,321 inpatient ABSSSI cases for the year 2011.^{14}
We calculated the total number of patients hospitalized with ABSSSIs that do not die in a given year by subtracting those who die in that year from the total number of ABSSSI patients. This number can then be subtracted from the estimated total number of hospital admissions for ABSSSI in 2011, 726,321 (explained above), to get 724,397 surviving ABSSSI hospital patients.
QALYs Lost per Case
To calculate lost QALYs for patients who have an ABSSSI but recover, we first searched the Tufts database and found a QALY weight of 0.642 for cellulitis, abscess, and wound infection, three major types of ABSSSI (though this QALY weight was for hospital patients infected with MRSA and therefore might represent cases on the more serious end of the severity spectrum) (Lee, et al., 2010). As with ABOM, we then adjusted the QALY weight by period of illness.
The average length of inpatient stay for patients hospitalized for an SSTI is 6.1 days (Menzin, et al., 2010). However, many skin infection patients are treated in both inpatient and outpatient settings, and length of hospital stay does not capture additional days spent sick or recovering outside the hospital. The mean number of days of episode duration is 24.4 days, which includes time spent in both inpatient and outpatient treatment settings (Marton, et al., 2008). Using 24.4 days as the illness period, we calculated the lost QALYs per patient to be 0.02393 as:
Total QALYs Lost due to Morbidity
Given that lost QALYs per ABSSSI case is 0.02393 and the total number of ABSSSI cases that do not result in death in the US is around 724,397, we computed the total annual QALYs lost due to ABSSSI morbidity to be 17,336 in the US.
Morbidity Cost
To calculate VSLYbased illness costs (for patients who do not die), we first calculated an average VSLY weighted by ABSSSI incidence by age group (available from Edelsberg, et al., 2009). This weighted average VSLY is roughly $365,500, which is then multiplied by the average lost QALYs per patient (0.02393) to arrive at $8,749 per patient. The total morbidity cost due to ABSSSI is then $6.3 billion (= $8,749 × 724,397) per annum.
^{14} The total number of ABSSSI cases—including patients who are treated in the outpatient setting only—is, however, far greater. Hersh, et al. (2008) examined visits by patients with SSTIs to physician offices, hospital outpatient departments, and emergency departments using NAMCS and NHAMCS and found that the overall rate of visits for SSTIs was 48.1 visits per 1000 population in 2005, totaling 14.2 million visits. As patients with skin infections are likely to visit these healthcare settings multiple times over the course of their SSTI episode, it is necessary to divide the total number of visits by the average number of visits per episode to arrive at the number of episodes per year. According to Marton, et al. (2008), who analyzed skin and skin structure infections caused by Staphylococcus aureus using managed care claims data for the years 20022005, the mean number of physician visits per episode was 6.3. Thus, 14.2 million outpatient visits divided by 6.3 visits per episode equals roughly 2.3 million episodes per year in 2005, or 778.1 per 100,000 population. Thus, the estimates presented herein constitute a lower bound.


3.6.5.3 Cabp

Total Number of Cases that do not Result in Death
We obtained the number of cases per year from the literature on communityacquired pneumonia and publicly available survey data. Using the National Health and Nutrition Examination Survey (NHANES) III, Niederman, et al. (1998) estimate the total number of CAP cases to be 5.6 million per year, or 2.3 percent of the U.S. population. Of these 5.6 million patients, Niederman, et al. (1998) report that 1.135 million are treated as inpatients, and the remaining 4.5 million are treated as outpatients. The National Hospital Discharge Survey (NHDS) (2009), available from the Centers for Disease Control and Prevention (CDC) website, arrives at a similar total of 1.145 million discharges of patients treated for pneumonia, or a rate of 37.4 per 10,000 population. Applied to the U.S. population in 2011, this rate yields an inpatient case count of approximately 1.17 million (National Hospital Discharge Survey, 2009), though these estimates are not limited to pneumonia cases with bacterial causative agents. Subtracting the total number of deaths (51,683) from this estimate (see Section 3.6.6.3), yields a survivor count of approximately 1.12 million per year.
QALYs Lost per Case
We searched the Tufts database for pneumonia and found reasonable QALY weights to be 0.85 for the period of hospitalization and 0.90 for the posthospitalization period of convalescence (Pepper & Owens, 2002). We then adjusted these weights by period of illness using the following equation:
The average length of stay in the hospital for pneumonia patients is reported in Pepper & Owens (2002) to be 4 days. However, length of hospital stay does not capture additional days spent sick or recovering outside the hospital. Pepper & Owens (2002) also estimate that healthy young adults miss approximately 9 work days due to pneumonia that is treated in the hospital, which includes 4 days in the hospital and 5 days of convalescence. Depending on what day a person gets sick, this may include one or two weekends, so we added 3 days to this convalescence period (1.5 weekends). Thus, the lost QALYs per patient came out to be 0.00384 computed as:
Total QALYs Lost due to Morbidity
Given that lost QALYs per CABP case is 0.00384 and the total number of CABP cases that do not result in death in the US is around 1.12 million, we computed the total annual QALYs lost due to CABP morbidity to be 4,295 in the US.
Morbidity Cost
To calculate VSLYbased illness costs (for patients who do not die), we took the VSLY for the age group containing the average age of a pneumonia inpatient (age 61, VSLY of $290,150), and multiplied it by the average lost QALYs per patient (0.00384) to arrive at a cost of $1,113 per patient. The total morbidity cost due to CABP was then computed at $1.2 billion (= $1,113 × 1,118,000) per annum.


3.6.5.4 Ciai

Total Number of Cases that do not Result in Death
Estimates of the number of cases of CIAIs each year in the U.S. were not readily available in the literature. Therefore, we estimated incidence using the rate of 2.3 cases of secondary intraabdominal infections (sIAI) per 10,000 personyears reported in a Netherlandsbased study (Sturkenboom, et al., 2005). Using a database of pharmacy dispensing records from community pharmacies linked to hospitalization records, the authors identified potential cases of sIAI on the basis of a primary discharge diagnosis with one of the following International Classification of Diseases, ninth revision (ICD9CM) codes: 475, 540–543, 562, 567, 569, 574–577, 614.5, 997.4, 998.2, E8782, and E8783. The authors then excluded “all potential cases that did not receive an intraabdominal surgical intervention to establish the diagnosis sIAI or antibacterial drug treatment during their hospital admission.” Finally, a clinician and an epidemiologist reviewed the hospital discharge letters associated with the remaining cases to verify that they met the case definition used by the authors (cholecystitis with rupture; diverticular abscess; appendiceal perforation and periappendiceal abscess; acute gastric and duodenal perforation operated within 24 hours; perforation of intestines; traumatic perforation of the intestines; or intraabdominal abscess). To obtain an estimate of the number of U.S. cases per year, we applied the rate of 2.3 cases per 10,000 personyears to the 2011 U.S. population, resulting in 72,043 cases. Subtracting the total number of deaths (14,136) from this estimate (see Section 3.6.6.4), results in around 57,489 surviving CIAI hospital patients per year.
QALYs Lost per Case
We searched the Tufts database for utility weights related to intraabdominal infections and found reasonable QALY weights to be 0.50 for the period of hospitalization and 0.85 for the posthospitalization period of convalescence (Richards & Hammitt, 2002). We then adjusted the utility weights by period of illness using the following equation:
The average length of stay in the hospital for complicated intraabdominal infections is estimated in various pharmacoeconomic studies to be around 10 days (Cattan, et al., 2002; Sturkenboom, et al., 2005; Walters, Solomkin, & Paladino, 1999). To capture additional days spent sick or recovering outside the hospital, we used 21.8 days as an average length of the posthospital convalescence period based on the average length of convalescence after appendectomies (National Center for Health Statistics, 1963). Thus, the lost QALYs per patient were estimated at 0.002266 as:
Total QALYs Lost due to Morbidity
Given that lost QALYs per CIAI case is 0.00266 and the total number of CIAI cases that do not result in death in the US is around 57,500, we computed the total annual QALYs lost due to CIAI morbidity to be 1,632 in the US.
Morbidity Cost
To calculate VSLYbased illness costs (for patients who do not die), we took the VSLY for the age group containing the median age of a CIAI inpatient (age 53, VSLY of $561,250) (Sturkenboom, et al., 2005), and multiplied it by the average lost QALYs per patient (0.02266) to arrive at $12,717 per patient. The total morbidity cost due to CIAI was then computed at $731.1 million (= $12,717 × 57,489) per annum.


3.6.5.5 Cuti

Total Number of Cases that do not Result in Death
Assessing the incidence of CUTI is difficult because urinary tract infection is not a reportable disease in the United States (Foxman, 2002). Total number of cases per year was obtained from the literature on urinary tract infections. We estimated cases of communityacquired CUTI separately from cases of hospitalacquired (nosocomial) UTI.
To arrive at a number of cases for communityacquired CUTI, we assumed that all inpatient hospitalizations where the primary diagnosis was urinary tract infection were cases of communityacquired CUTI. Griebling and Freedmen (2007) analyzed the 2000 National Inpatient Sample and estimated a total of 403,814 inpatient hospital stays for men, women and children with UTI as the primary diagnosis in 2000. They provide rates of inpatient stays by age and gender breakdowns. For comparison, we replicated this analysis with the 2009 NIS using the list of ICD9 codes for urinary tract infection provided by the authors. For 2009, we estimated a total of 543,140 inpatient hospital stays for men, women and children with UTI as the primary diagnosis. When divided by the 2009 U.S. population, this is equivalent to a rate of 17.7 per 10,000 population. The National Hospital Discharge Survey (NHDS) (2009), available from the Centers for Disease Control and Prevention (CDC) website, arrives at a similar total of 575,000 discharges of patients treated for urinary tract infection in 2009, or a rate of 18.8 per 10,000 population. For our calculations, we applied the 2000 rates of inpatient stays for men, women, and children to the U.S. population totals for those categories to arrive at a total an inpatient count of approximately 470,915 cases of communityacquired CUTI in 2011 (National Hospital Discharge Survey, 2009).
According to a 2007 public health report that uses data from the National Nosocomial Infections Surveillance (NNIS) system (conducted by the Centers for Disease Control and Prevention), supplemented by data from the National Hospital Discharge Survey and the American Hospital Association Survey, there were 561,667 cases of healthcareassociated urinary tract infection in 2002 (Klevens, et al., 2007), which is equivalent to a rate of 195.4 per 100,000 population. Applied to the 2011 U.S. population, this rate results in an estimated 611,935 cases for the year 2011.
We subtracted the estimated deaths from the estimated total number of CUTI cases in 2011 to get surviving CUTI hospital patients (448,311 and 597,675 for communityacquired and hospitalacquired, respectively, for a total of 1,045,986 CUTI cases).
QALYs Lost per Case
From the Tufts database, we found a QALY weight of 0.73 as a mean utility weight for bladder infections (Gold, Franks, McCoy, & Fryback, 1998). This value is relatively consistent with a 0.2894 disutility (0.7106 utility) for “chronic dysuria, vaginitis and other symptoms” from a different costutility analysis of UTIs in ambulatory women, which also lists a disutility of 0.3732 for pyelonephritis (Barry, Ebell, & Hickner, 1997). As was done for other indications, we adjusted this weight by period of illness.
We calculated lost QALYs separately for communityacquired and hospitalacquired CUTI. To calculate lost QALYs for communityacquired CUTIs, we used an average inpatient length of stay of 4 days. This number represents a weighted average length of stay for adults 18 to 64 years of age, who represent the bulk of the working population. Although there may be some outpatient recovery time following hospitalization for patients who have suffered complicated urinary tract infections, that information is not readily accessible in the literature, so outpatient recovery time is not included in these estimates. Thus, the lost QALYs per patient for communityacquired CUTI were estimated as:
As nosocomial CUTIs occur, by definition, in patients who are already hospitalized for other conditions, it is necessary to differentiate the length of time by which the episode of hospitalacquired CUTI extends the patient’s stay from the entire length of stay due to all conditions from which the patient suffers. According to the literature, nosocomial UTI lengthens the period of hospitalization by 1 to 4 days (Lai & Fontecchio, 2002), so we used the midpoint of that range (2.5 days) for the purposes of our calculations. Again, although there may be some outpatient recovery time following hospitalization for patients who have suffered from nosocomial CUTI, that information is not readily accessible in the literature, perhaps because it is so difficult to distinguish between recovery time for CUTI and recovery time for the patient’s underlying illness(es). Therefore, we do not include any outpatient recovery time in our estimates. Using 2 days as the illness period, we calculated the lost QALYs per patient to be 0.00185 as:
Total QALYs Lost due to Morbidity
Given that lost QALYs per communityacquired CUTI case is 0.00296 and the total number of communityacquired CUTI cases that do not result in death in the US is around 448,000, we computed the total annual QALYs lost due to communityacquired CUTI morbidity to be 1,327 in the US. Similarly, the total annual QALYs lost due to hospitalacquired CUTI was computed as 1,106 (= 0.00185 × 597,675) per year. This yielded a total of 2,432 QALYs lost due to CUTI overall per annum.
Morbidity Cost
To calculate VSLYbased illness costs (for patients who do not die) we first calculated a weighted average WTP to avoid CUTI, which is equal to the VSLY weighted by CUTI incidence by age group in 2011. To approximate the age distribution of CUTI incidence, we calculated the age distribution from 2000 HCUP data on inpatient stays with a primary diagnosis of UTI (U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2007). The resulting weighted average VSLY is roughly $325,000 which is then multiplied by the average lost QALYs per patient (0.00296 and 0.00185 for communityacquired and hospitalacquired, respectively) to arrive at $961 per communityacquired CUTI patient and $601 per hospitalacquired CUTI patient, for a weighted average of $758 per patient for a CUTI case. The total morbidity cost due to CUTI was then computed at $792.9 million (= $758 × 1,045,986) per annum.


3.6.5.6 HABP/VABP

Total Number of Cases that do not Result in Death
We obtained the number of cases per year from the literature on HABP/VABP. HABP is not a reportable illness, and diagnosis may be complicated due to overlap with other respiratory tract infections, especially for mechanically ventilated patients; therefore, determining incidence for HABP and VABP is difficult (American Thoracic Society; Infectious Diseases Society of America, 2005). However, many sources cite available data suggesting that these infections occur at a rate of 5 to 10 cases per 1,000 hospital admissions (American Thoracic Society; Infectious Diseases Society of America, 2005; McEachern & Campbell, 1998), or roughly 300,000 cases per year, as McEachern & Campbell (1998) report. To get a more uptodate estimate, we applied this rate to the 36.1 million inpatient discharges in 2009 (from the National Hospital Discharge Survey), which yields a range of 180,500 to 361,000 HABP/VABP cases per year, with the midpoint of the range equal to 270,750.
According to a 2007 public health report (the same one used to estimate the number of hospitalacquired CUTI cases), there were 250,205 cases of healthcareassociated pneumonia in 2002 (Klevens, et al., 2007), which is equivalent to a rate of 87.0 per 100,000 population. Applied to the 2011 U.S. population, this rate results in an estimated 272,598 cases for the year 2011. Though the 2007 report is not specific with regard to the types of infections that are included, the estimate of 272,598 cases per year is very close to the midpoint of the range calculated above (270,750). It is also similar to the 300,000 figure reported by McEachern & Campbell (1998). Therefore, we determined that 272,598 was a reasonable point estimate of HABP/VABP cases in 2011. Subtracting the total number of deaths (81,779) from this estimate (see Section 3.6.6.6), results in 190,818 surviving HABP/VABP hospital patients.
QALYs Lost per Case
From the Tufts database, we found a QALY weight of 0.83 for VABP (Shorr, Susla, & Kollef, 2004), which we then adjusted by period of illness.
As HABP/VABP occur, by definition, in patients who are already hospitalized for other conditions, it is necessary to determine the length of time by which the episode of HABP or VABP extends the patient’s stay (as opposed to the entire length of stay due to all conditions from which the patient suffers). According to the literature, HABP/VABP lengthens the period of hospitalization by 7 to 10 days (McEachern & Campbell, 1998; Sampathkumar, 2009), so we use the midpoint of this range for the purposes of our calculations (8.5 days). Though there may be some outpatient recovery time following hospitalization for patients who have suffered from HABP/VABP, that information is not readily accessible in the literature, perhaps because it is so difficult to distinguish between recovery time for HABP/VABP and recovery time for the patient’s underlying illness(es). Therefore, we do not include any outpatient recovery time in our estimates. Using 8.5 days as the illness period, we calculated lost QALYs as:
Total QALYs Lost due to Morbidity
Given that lost QALYs per HABP/VABP case is 0.00396 and the total number of HABP/VABP cases that do not result in death in the US is around 191,000, we computed the total annual QALYs lost due to HABP/VABP morbidity to be 756 in the US.
Morbidity Cost
To calculate VSLYbased illness costs (for patients who do not die), we first selected an appropriate VSLY based on average patient age, as we do not have a breakdown of incidence by age group from the literature or other sources (as discussed above). The VSLY for people aged 55 to 62 is $290,150, which is then multiplied by the average lost QALYs per patient (0.00396) to arrive at $1,149 per patient. The total morbidity cost due to HABP/VABP was then computed at $219.2 million (= $1,149 × 190,818) per annum.

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