Emerging Infectious Diseases
[Volume 5 No.6 / November - December 1999]

   Research

   Using Automated Pharmacy Records to Assess the
   Management of Tuberculosis

   Girish S. Subramanyan,* Deborah S. Yokoe,* Sharon
   Sharnprapai, Edward Nardell, Eugene McCray, and
   Richard Platt*

   *Brigham and Women's Hospital, Boston, Massachusetts,
   USA; Massachusetts Department of Public Health,
   Jamaica Plain, Massachusetts, USA; Centers for Disease
   Control and Prevention, Atlanta, Georgia, USA; Harvard
   Medical School, Harvard Pilgrim Health Care, Boston,
   Massachusetts, USA


    We used automated pharmacy dispensing data
    to characterize tuberculosis (TB)
    management for 45 health maintenance
    organization (HMO) members. Pharmacy
    records distinguished patients treated in
    HMOs from those treated elsewhere. For
    cases treated in HMOs, they provided useful
    information about appropriateness of
    prescribed regimens and adherence to
    therapy.



   Health-care coverage, especially from health
   maintenance organizations (HMOs), often includes
   pharmacy benefits. Pharmacy dispensing records can
   identify cases of tuberculosis (TB) unknown to the
   public health system (1). In this article, we examine
   the utility of automated pharmacy dispensing data in
   assessing the quality of management of active TB and
   patients' compliance with recommended therapy.

   Methods

   We used automated pharmacy dispensing records to
   characterize therapy in 45 cases of active TB diagnosed
   from January 1, 1992, through June 30, 1996, at Harvard
   Pilgrim Health Care, a mixed model HMO in New England.
   These were all known cases of TB in a sample of 350,000
   HMO members (1,2); all met the Centers for Disease
   Control and Prevention's (CDC) surveillance case
   definition (3). Cases were drawn from the 90% of HMO
   members with pharmacy benefits.

   We identified all dispensings of isoniazid, rifampin,
   pyrazinamide, ethambutol, streptomycin, ethionamide,
   kanamycin, cycloserine, capreomycin, and
   para-aminosalicylic acid (PAS). We also reviewed the
   full medical records. Empiric regimens, i.e., those
   dispensed before susceptibility results were known, and
   final treatment regimens were graded for consistency
   with American Thoracic Society (ATS) and CDC guidelines
   in effect at the time of diagnosis (4,5). Two measures
   of the adequacy of therapy were calculated. 1) The
   standard regimen dispensed is a percentage calculated
   by comparing the cumulative dose of each drug dispensed
   with the total recommended. Each drug received equal
   weight to a maximum of 100% per drug, as noted in the
   following formula for a three-drug regimen: percent
   standard regimen = ([D1/SR1] + [D2/SR2] + [D3/SR3]) x
   (100/3), where Dx is the cumulative dose dispensed of
   drug X and SRx is the recommended total dose. Patients
   with a score >/=80% were considered to have received an
   appropriate amount of antituberculosis medications (6).
   2) The days without medication (identical to the
   "MED-OUT" adherence index validated for other
   medications) (7), for isoniazid or another drug
   required for the entire duration of treatment, is a
   percentage calculated by dividing the total number of
   days without medication (based on medication refill
   intervals and quantities dispensed) by the number of
   days between the first and last dispensing. The last
   refill does not influence this calculation. All the
   preceding calculations included all medicine dispensed
   to a patient, from all pharmacies required to report
   dispensing to the HMO to be reimbursed.

   Results

   Medical records indicated that 27 (60%) of 45 TB cases
   were treated solely by HMO providers (Table 1); nearly
   all remaining patients received their non-HMO care in
   public health-funded TB programs. Thirty-seven (82%)
   cases received empiric regimens through pharmacies
   reimbursed by the HMO. In 34 (92%) instances, the
   empiric regimen dispensed was appropriate; for the
   remainder, empiric regimens contained too few drugs.
   Twenty-six (96%) of the 27 solely HMO-treated cases
   were prescribed a final antituberculosis regimen that
   was adequate in agents used, doses prescribed, and
   duration of treatment.


Table 1. Characteristics of tuberculosis cases


In 15 of the 18 cases treated at least
partially outside the HMO, patients received
some antituberculosis medication from
pharmacies reimbursed by the HMO. In 14 of   
these cases, patients received medications only   
once or twice. A cutoff value of 70 days of  
drug dispensing through HMO-reimbursed  
pharmacies differentiated HMO-treated cases  
from cases treated in other settings. Among  
HMO-treated cases, 26 (96%) of 27 patients   
received medications for 70 days, compared with   
1 (6%) of 18 who were at least partially
treated outside the HMO (Figure 1) (RR = 17, 
95% confidence interval [CI] 3 to 117, p<0.0001) (8). In HMO cases, median duration of dispensing from HMO pharmacies was 189 days (interquartile range: 148 days to 291 days) and  
the median standard regimen dispensed score was   
99% (interquartile range: 86% to 100%). In   
cases outside the HMO, median duration of
dispensing through HMO-reimbursed pharmacies was 1 day
(interquartile range: 0 days to 32 days), and the median standard regimen dispensed score was 24% (interquartile range: 17% to 40%). Figure 2 shows the relationship between the appropriateness of the amount of medications dispensed and the timeliness of medication refills. In 4 (15%) of 26 HMO-treated cases, standard regimen dispensed scores were <80%, and days without medication scores were >30%. In only one of these four undertreated cases did the treating
physician document nonadherence. Two other patients who received 100% of a standard regimen with unremarkable refill intervals were noted as noncompliant in physicians' medical records.

Figure 1. Pharmacy dispensing profiles of tuberculosis (TB) cases treated in the health maintenance organization (HMO) and outside the HMO. Standard regimen (percentage) and duration of dispensing of antituberculosis medication dispensed for TB cases. A cutoff value of >/=70 days of medication dispensed from HMO-reimbursed pharmacies, as assessed from automated pharmacy records, differentiated
HMO-treated cases from cases at least partially treated outside the HMO. 

Figure 2. Appropriateness of the amount of antituberculosis medications dispensed and the timeliness of
medication refills. Percentage of standard regimen dispensed is plotted against percentage of days
without antituberculosis medication for tuberculosis cases treated in the health maintenance
organization.


Conclusions

Automated pharmacy data provided useful
information both about physicians' intended 
management of TB and about patients' adherence   
to prescribed therapy. The ability to monitor    
these aspects of TB care efficiently is
particularly important when care is    
decentralized or a substantial proportion of
patients receive care from more than one    
provider. We were able to determine that in 
nearly all cases appropriate initial or empiric
regimens were prescribed, and that in most  
cases managed by HMO providers full 
ATS/CDC-recommended regimens were dispensed.
This approach was thus more informative and
efficient than prior study methods that assessed prescribed regimens by reviewing patients' medical records (9). Many HMOs and other insurers routinely monitor pharmacy dispensing records for various reasons. While the initial cost of creating a routine monitoring report varies, the marginal cost of running it periodically is usually negligible. This allows 100% surveillance of therapy,
compared with manual record review, which is more expensive even when only a sample of records is reviewed. Additional investigation would determine whether this method will be helpful for other infectious diseases, such as pelvic inflammatory disease.

In using a pharmacy-based system to monitor adherence to therapy, it is important to identify cases treated solely within a delivery system, since automated pharmacy information is reliably complete only for these persons. Restricting to patients with at least 70 days of therapy accomplishes this, since it excludes those who receive empiric regimens within one health system and then complete
their care at another. Most care delivered by non-HMO providers was provided by public health clinics. Potential physician incentives for transfer of care included closer monitoring of therapy by experts in TB treatment,  particularly in difficult-to-manage cases. Patients' incentives included free medications provided by the
department of public health. Although all patients described here had pharmacy benefits, the cost to the patients of copayments for a standard treatment regimen would have been $75 to $200.

Monitoring automated pharmacy records of patients treated for TB was an efficient adjunct for monitoring adherence but did not entirely replace providers' assessments documented in the medical records. It also provided no advantage in settings that used directly observed therapy, which is not routinely used in Massachusetts.

Pharmacy records may be used to contribute to management of TB in two ways: in real time, to identify suboptimal regimens and noncompliant patients and periodically, to assess overall appropriateness of care. In real time, one might monitor the dispensing of antituberculosis medications for confirmed cases of TB, intervening if necessary with physicians to ensure that appropriate regimens are used and with patients to minimize gaps in dispensing. Identifying noncompliant patients in a regular and timely manner could allow for interventions (e.g., directly observed therapy) to improve adherence to the treatment regimen. Such oversight could be coordinated with or overseen by public health
agencies. Coordination between delivery systems and public health agencies is expected to become an important element of TB control (10). Periodic assessment of dispensing records can also provide a simple, efficient measure of the overall appropriateness of TB care in a wide array of settings. These measures would allow targeting of
resources to improve organizations' management of TB. If these findings are confirmed in other settings, routine monitoring of dispensing of antituberculosis medications may be useful as an adjunct to other methods of assessing and ensuring appropriate therapy.

Acknowledgment

We thank Claire Canning for her assistance with this study.

This study was supported by CDC Contract 200-95-0957-010 and the Harvard Pilgrim Health Care Foundation.

Dr. Subramanyan was a research fellow at the Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts, and a student at Harvard Medical School when he performed this work. He is currently a resident at the University of California, San Francisco.

Address for correspondence: Deborah Yokoe, 181 Longwood Ave., Boston, MA 02115, USA; fax: 617-731-1541; e-mail:
deborah.yokoe@channing.harvard.edu.

References

1. Yokoe DS, Subramanyan GS, Nardell E, Sharnprapai S, McCray E, Platt R. Supplementing tuberculosis surveillance with automated data from health maintenance organizations. Emerg Infect Dis 1999;5:779-87.

2. Subramanyan GS, Yokoe DS, Sharnprapai S, Tang Y, Platt R. An algorithm to match registries with minimal disclosure of individual identities. Public Health Rep 1999;114:91-3.

3. Centers for Disease Control and Prevention. Case definitions for infectious conditions under public health surveillance. MMWR Morb Mortal Wkly Rep 1997;46:40-1.

4. Bass JB Jr, Farer LS, Hopewell PC, O'Brien R, Jacobs RF, Ruben F, et al. Treatment of tuberculosis and tuberculosis infection in adults and children. Am J Respir Crit Care Med 1994;149:1359-74.

5. American Thoracic Society. Treatment of tuberculosis and
tuberculosis infection in adults and children. American Review of Respiratory Disease 1986;134:355-63.

6. Fox W. Whither short-course chemotherapy? British Journal of Diseases of the Chest 1981;75:331-57.

7. Steiner JF, Koepsell TD, Fihn SD, Inui TS. A general method of compliance assessment using centralized pharmacy records: description and validation. Med Care 1988;26:814-23.

8. EpiInfo [computer program]. Version 6.04b. Atlanta (GA): Centers for Disease Control and Prevention; 1997.

9. Migliori GB, Spanevello A, Ambrosetti M, Neri M. Surveillance of tuberculosis treatment prescriptions in Italy. The Varese TB Study Group. Monaldi Arch Chest Dis 1998;53:37-42.

10. Halverson PK, Mays GP, Miller CA, Kaluzny AD, Richards TB. Managed care and the public health challenge of TB. Public Health Rep 1997;112:22-8.

Emerging Infectious Diseases
National Center for Infectious Diseases
Centers for Disease Control and Prevention
Atlanta, GA

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