Re: Letter written in reaction to "Pregabalin prescriptions in the United Kingdom: a drug utilisation study of The Health Improvement Network (THIN) primary care database" by Pottegard et al. The authors (Asomaning et al. respond
To the Editor: We thank the authors Potteg ard et al. for their interest in our recent publication (1) summarising the results of our study of the patterns of pregabalin use in The Health Information Network (THIN) a well established UK database commonly utilised for pharmacoepidemiological and outcomes research (2 4) In their letter, Potteg ard et al. raised two potential issues, specifically: (i) the use of prescribed dose of single prescriptions compared with dispensed dose for the full pattern of dispensings for each individual and (ii) the sampling of patients from a general practice (primary care) database that does not hold data on secondary and tertiary care. In their opinion, both issues will result in a bias towards the null in estimates of the proportion of patients using pregabalin above licensed dosages. As brief background, based on a small number of case reports of potential abuse of alpha 2 delta antiepileptic drugs from some European countries, the Committee for Medicinal Products for Human Use/European Medicines Agency (CHMP/EMA) adopted a conclusion on 19 August 2010 that a Drug Utilization Study (DUS) to further investigate the potential for abuse with pregabalin be conducted by Pfizer, the marketing authorisation holder. As agreed with the CHMP/EMA, two diverse databases were utilised to represent the varying healthcare systems and settings in Europe: the THIN primary care database and the Swedish national health and population registers. Therefore, one important rationale for selecting the THIN database was to look at prescribing patterns in a United Kingdom (UK) primary care setting to complement the Swedish data representing primary and hospital prescribing patterns in a Nordic country. Both databases have individual strengths and weaknesses, and both are considered well validated and well recognised for pharmacoepidemiologic research with numerous publications. (2 15) Regarding the first issue raised by Potteg ard et al. i.e. the definition of pregabalin exposure in our study, in a 2011 presentation, Thompson et al. (16) demonstrated a very high correlation between prescribing recorded in THIN data and drug dispensing in England. Across all drug classes, the mean annual prescription redemption rate (calculated as redeemed prescription/issued prescription over same period) for each year studied (2005 2008) exceeded 98% If there is any limitation to our use of prescribed data instead of dispensed data in the THIN data, the effect is most likely to be minimal. It is also important to note that having at least a single prescription was an inclusion criterion for the THIN study (1) However, the study did not consist only of patients with a single prescription as Potteg ard et al. suggest. Close to a quarter of patients (24.2% with dosing information in the DUS had a single prescription and 29.6% of patients had more than 10 prescriptions [Calculated in response to Potteg ard et al. data on file] Regarding the second issue raised by Potteg ard et al. i.e. that primary care data sources may underestimate exposure, in the UK, the general practitioner (GP) is the strict entry point (gate keeper) to healthcare (17) If a drug is initiated in hospital, the patient will initially be provided a small amount to use during the short period until a repeat prescription is written by the GP (18) Therefore, in the UK the lack of hospital data is unlikely to result in any significant bias in this study in determining the usage pattern of a drug such as pregabalin that is mainly used in the outpatient setting over long duration. We note the results from the other EMAagreed DUS study of pregabalin use by Boden et al. (19) based on data extracted from the Swedish national registers and included primary, secondary and tertiary care centres, showed (Table 1) that 'there were only minor differences in the distribution of the type of prescriber between those who prescribed doses within the recommended range and those who were prescribed doses exceeding it' This result suggests that, at least in Sweden, the results of using a primary care only data source would not substantially overor underestimate pregabalin usage in other care settings, and combined with the GP gatekeeper system in the UK, contradicts the assertion by Potteg ard et al. that 'the restriction to primary care prescribing, will likely result in estimation of pregabalin use above licensed doses that do not reflect actual use' In the THIN DUS (1) the average daily dose (ADD) of pregabalin was calculated as the average amount over their entire treatment episodes for each patient. In the Swedish DUS [Pfizer Swedish DUS report to the EMA, data on file] (19) the ADD was calculated in two different ways, i.e. as the average amount between the 2nd and 3rd dispensing dates and as the average amount when following patients over their entire treatment episodes. Of the 48,550 patients who had filled more than two prescriptions, 4130 (8.5% had been dispensed amounts above a dose of 600 mg/day when assessed as the purchased amount between the 2nd and 3rd dispensing dates. The corresponding proportion when assessed over entire treatment episodes was 5.7% (3398/60,270) [Pfizer Swedish DUS report to the EMA, data on file] (19) In a Danish pregabalin DUS (20) the ADD was calculated over the first 6 and 12 months of each prescription. These differences in methods of calculating the ADD may partly account for the differences in the proportion Table 1 Sociodemographic and clinical factors by estimated daily dose of pregabalin within or above the recommended dose range
International journal of clinical practice