Cost-effectiveness of antibiotics for COPD management: observational analysis using CPRD data

Discussion

The retrospective, observational cost-effectiveness analysis using almost 43 000 EHRs from the CPRD found that patients who were prescribed antibiotics during a GP consultation for a COPD exacerbation had lower subsequent GP consultations, hospitalisations and infections over a 4 week period following the exacerbation when compared to patients who were not prescribed antibiotics. No significant difference in subsequent antibiotics, all referrals and community respiratory team referrals was identified. Our findings showed that patients who received antibiotics had lower costs due to fewer GP visits, hospital inpatient stays, infections, referrals, community respiratory team referrals and subsequent antibiotics prescriptions, although it should be noted that not all demonstrated significant differences.

It was useful to compare the 4 week findings of the base-case analysis with those in the longer term, i.e. at 3 months and 12 months. The findings remained the same for our 3 month and 12 month analyses, in terms of consistently lower mean costs resulting from lower resource use for the antibiotics group. The only exception was for infections, which were marginally higher (raw unadjusted mean only) for those prescribed antibiotics in the 12 month analysis, although not statistically significant.

There may be several reasons for clinicians in primary care not prescribing antibiotics: clinical presentation, previous experience, patient choice, but also some or many patients may not have had a diagnostic code of COPD on their records, or a past apparently “normal spirometry”. On the one hand there is evidence and pressure on GPs to reduce and/or avoid using antibiotics, yet in COPD exacerbations, the threshold for initiating antibiotics is necessarily lower to avoid potential complications.

The recent Cochrane review on the use of antibiotics for COPD exacerbations found there to be no statistically significant effect on hospital length of stay in inpatients [4] and no specific healthcare resource use was reported by the included trials in terms of the type analysed in this study. As previously stated, the review included studies that mainly focused on patients with more severe COPD exacerbations who were referred to hospitals, rather than a more diverse group of patients in general practice. Our observational analysis findings add to the evidence base regarding the impact of antibiotics prescription for COPD patients experiencing exacerbations in primary care. The analysis was based on a large patient sample, where resource use was explored for those who attended their general practice regarding a COPD exacerbation. Hence, we were able to evaluate actual patient data rather than making assumptions regarding resource utilisation. It should also be noted that the inclusion of those patients with COPD who have never smoked could be classed as a limitation, and the diagnosis for the 11% of patients that this applied to could be considered to be questionable.

Data were available regarding the reason for inpatient stay for the hospitalisations data, so, in theory, it would have been possible to cost more precisely according to the particular health resource group (HRG) code. However, due to the volume of codes for which costs would need to have been attached, a representative cost was applied instead. This is, of course, a simplification, and it should be kept in mind when interpreting the results. When attaching a cost to the relevant CPRD code, the closest match available was taken from NHS Reference Costs, as in some cases the CPRD and HRG codes did not correspond exactly. Assumptions were made around the estimation of costs for infections and antibiotics prescriptions, based on the available data. The use of the several assumptions that were made around the costs in the study is a limitation to note. The review on antimicrobial resistance by O'Neill [8] highlights the substantial potential impact of rising drug resistance. However, the cost of antimicrobial resistance developing from antibiotic use was not included in the present analysis, and this is acknowledged as a limitation.

The analysis also assumed that the patients in the “antibiotics” group who were prescribed antibiotics at the index GP consultation actually received the antibiotics that they were prescribed; however, there is the possibility that they did not. Although data regarding whether patients were prescribed a “rescue pack” were available, the information was related to the date of prescribing and not the date it was used by a patient. Data were not provided regarding the number of exacerbations experienced prior to the index visit, which would have been useful to analyse because those more frequent exacerbators are likely to have greater morbidity and healthcare utilisation, with GPs perhaps avoiding repeated antibiotic courses where possible. It is also worthy to note that the data set that we used may be biased, in that patients who are prescribed antibiotics may be more severe than patients who are not prescribed antibiotics, so the groups may be unbalanced in terms of patient characteristics. This highlights the importance of conducting an RCT in general practices that would remove such bias from an analysis.

Ideally, a cost-utility analysis would be conducted to generate the cost per quality-adjusted life-year (QALY) associated with antibiotics use. However, QALYs were not available for the population under analysis, so a cost-utility analysis was not undertaken. Future collection of quality-of-life values for such COPD exacerbation patients would be worthwhile.

There is a lack of spirometric data in making the diagnosis of COPD, with it being known that over a quarter of patients on GP COPD registers do not fulfil the spirometric criteria when retested [9]. The COPD diagnosis may thus not be robust. While COPD remains a diagnosis confirmed on spirometry, it is well known that patients aged over 45 years and long-standing smokers, with previous repeated chest infections, remain good surrogate markers for COPD diagnosis. It is also worthwhile to note that there was a high level of missing data for the COPD status variable reported.

Due to the limited information regarding COPD exacerbation events included in the study, the analysis relied on the coding of the encounter, which may not be fully accurate. This in turn means that it is not possible to gauge how unwell the patients in the two groups were compared to one another, which may affect their subsequent clinical course.

There was an issue with missing data in the study, particularly around patients' ethnicity. Missing data can be inherent in large database studies of COPD and, while they are not necessarily avoidable or detrimental, can affect interpretation of the results. The high level of missing data for some of the variables featured in the analysis should therefore be considered when interpreting the findings. In addition, although the analysis controlled for covariates believed to influence the results, there is the possibility of confounding due to further potential confounders not being controlled for. Other variables such as associated morbidity and medications, including the use of oral steroids, could have influenced the results.

There may be several reasons for clinicians in primary care not prescribing antibiotics: clinical presentation, previous experience, patient choice, but also some or many patients may not have had a diagnostic code of COPD on their records, or a past apparently “normal spirometry”. Other reasons may include indirect consultation over the telephone with a patient or carer, palliative care patients, recording issues following home visits, or the patient has their own supply of antibiotics previously provided. On the one hand there is evidence and pressure on GPs to reduce and/or avoid using antibiotics, but in COPD exacerbations, the threshold for initiating antibiotics is necessarily lower to avoid potential complications.

Nevertheless, the findings from this study, apart from highlighting the potential importance of GPs initiating antibiotics early in COPD exacerbations, also raise the issue of being vigilant and aware of the risks of not prescribing antibiotics leading to potential complications of hospitalisation and increased use of NHS resources. Although not a direct conclusion of this study, the findings nevertheless raise the need for careful clinical assessment and review of those patients with COPD exacerbations who are at the severe end of the spectrum.

In conclusion, a large observational patient data set derived from EHRs was used to illustrate the type of analysis that can be undertaken using trials that are carried out via the CPRD or similar databases. The use of antibiotics for patients who present to their GP with a COPD exacerbation was found to be dominant over (i.e. compared favourably with) the use of no antibiotics, as it resulted in cost savings and improved outcomes (i.e. reduced resource use, infections and subsequent antibiotics prescriptions). However, it should be noted that no significant differences were identified for subsequent antibiotics, all referrals and community respiratory team referrals. Our 4 week analysis suggests that the use of antibiotics for COPD exacerbations is a cost-effective alternative to not prescribing antibiotics for patients who present to their GP and remains cost-effective when longer time horizons of 3 months and 12 months are considered. It would be useful for a definitive trial to be undertaken in this area to determine the cost-effectiveness of antibiotics for COPD exacerbations.