Impact of removal and restriction of me-too medicines in a hospital drug formulary on in- and outpatient drug prescriptions: interrupted time series design with comparison group

The viability of public health services and their financing is one of the major global health policy debates [1‐3], due to the constant increase in costs [4]. Pharmaceutical provision accounts for 25–30% of the public budgeting of healthcare expenditure [5] and is considered to be the main cause of inefficiency in public health services [1].

The main factors involved in high pharmacy costs are the appearance of new drugs, the intensification of treatments, polytherapy, or their prices [6], the promotion of pharmaceutical companies [7, 8], and the induced prescriptions of hospital doctors to primary care doctors [9‐11].

Hospital drugs formularies are lists of drugs drawn up to optimise inpatient care and ensure clinically appropriate, safe and cost-effective access [12, 13], and are a common tool for rational drug use in developed countries [14‐16]. The growing supply of available drugs, many of which are so-called “me-too drugs” or drugs from the same family, and intense promotion by the pharmaceutical industry has made it necessary to limit these lists [7]. Although drugs formularies are not strictly mandatory, adherence to them by hospital prescribers tends to be very high [15‐18], ranging at maximum from 85% to 90% [16].

To our knowledge, there is little research [19‐21] evaluating the impact of a change in hospital formularies on outpatient prescription. Hence, the aim of this study was to evaluate the impact of withdrawing two low molecular weight heparins (LMWHs) from a hospital formulary (and restricting a third to the case where the only unrestricted prescription LMWH is contraindicated) on in- and outpatient LMWH prescribing.

Table 1 shows the population distribution of the intervention and control groups.

This is the first longitudinal controlled study to show that in-hospital LMWH prescribing has a major impact on out-of-hospital prescribing.

Our study intervention (which was in-hospital) led to an immediate decrease of almost 8% and a shift from upward to downward in the long-term trend of out-of-hospital expenditure per DDD. These results may well be of great interest to policymakers, as they indicate that hospitals are an important inducer of prescribing in primary care and, by extension, that changes in a hospital drugs formulary towards more efficient drugs can help reduce pharmaceutical costs, not only at an in-hospital but also at an out-of-hospital level [9, 10, 11, 19, 20, 35].

Our data indicate that the withdrawal of drugs from a hospital drugs formulary has an impact on out-of-hospital prescribing, both in the short and in the long term. An example of this is provided by bemiparin: in addition to registering an immediate reduction in use, it showed a shift in trend, from upwards before its removal from the hospital formulary to downwards thereafter. Similarly, the use of dalteparin, which showed a previous downward trend, registered an immediate significant reduction after the drug’s withdrawal.

Although there may be some residual use of some withdrawn medications, this is in line with other studies which indicate that adherence to drugs formularies by hospital health professionals, albeit very high (80–95%) [15‐17], is not 100%.

Our data indicate that the introduction of drug-use restrictions in a hospital formulary is associated with a reduction in that drug’s use at both an in- and out-of-hospital level. This is the case of tinzaparin, which, after being made subject to prior authorisation, immediately registered a 45.5% reduction in consumption in the hospital environment. These results are in line with studies that report a sharp decrease in the use of drugs rendered subject to prior authorisation [36‐41].

However, in addition to the restriction’s impact on in-hospital prescriptions, there was also an impact outside the hospital, with an immediate 9% reduction in tinzaparin use, despite the fact that the need for prior authorisation was not implemented at the outpatient level. Since, we were unable to locate any other study which analysed the impact of making a drug subject to prior authorisation at the in-hospital level on the prescription of that same drug at the out-of-hospital level (when, at the hospital level, such a drug was not subject to prior authorization), this would make our study the first to analyse such an impact.

At the outpatient level, nadroparin (the only LMWH that was not included in the hospital drugs formulary before the change) experienced no significant changes after the intervention. Moreover, nadroparin is the LMWH with the lowest out-of-hospital use, which further reinforces the theory that in-hospital prescribing has an influence on out-of-hospital prescribing, and is a similar result to that of other cross-sectional studies which report that, when hospitals include a given LMWH in the hospital drugs formulary, there is also greater use of that LMWH at the out-of-hospital level [19].

The finding that 95% of total SNHS expenditure on LMWHs corresponds to out-of-hospital use may be due to the fact that the number of ambulatory patients in the health area is much higher than the number of patients who are hospitalised at any given time and that out-of-hospital use is usually chronic, while in-hospital use tends to be acute. Furthermore, expenditure per DDD at the in-hospital level is lower than at the out-of-hospital level, as it can be subject to discounts. This would explain why the savings yielded by the change to the hospital drugs formulary during the study period correspond almost entirely to the out-of-hospital setting. Biosimilar enoxaparin was not yet being marketed in Spain by the time our study ended; however, once biosimilar enoxaparin [42‐44] is marketed in Spain, the savings could be even greater. The fact that costs correlate with consumption at an out-of-hospital but not at an in-hospital level and the large variations in expenditure per DDD in the in-hospital setting (see Fig. 3) may both be related to the discounts offered by pharmaceutical companies to hospitals, as described in other studies [11, 14].

The results of our study indicate that the withdrawal of inefficient drugs from a hospital drugs formulary at an out-of-hospital level and the application of out-of-hospital costs when deciding on the inclusion of a drug in the hospital drugs formulary are aspects that should be taken into account by the committees that decide on the composition of such formularies. Although gross in-hospital spending on a group of drugs may be very small compared to what is spent on an out-of-hospital basis for the same group (e.g., LMWHs, anti-hypertensives or proton pump inhibitors), in-hospital formulary changes may have a considerable induced impact on outpatient drug spending.

Pharmacy and Therapeutics Committees play a major role in establishing a local, safe, and effective drug policy [45‐47], yet we found no studies addressing how and when a drug should be withdrawn from a hospital drugs formulary. Our results suggest incorporating the withdrawal of inefficient drugs as another essential function. In this connection, it should be noted that this function of evaluating the withdrawal of drugs from the hospital drugs formulary comes at practically zero cost to the health organisation.

To our knowledge, this is the only controlled longitudinal study to analyse the effect of removing a compound from a hospital drugs formulary in two care scenarios, i.e., inpatient and outpatient, and shows that the effect of hospital-induced prescribing on the primary care setting can be modified to guide the latter towards a more efficient drug provision.

The fact that this study was controlled had the advantage that, if there had been changes in consumption or external factors (publications of guides, articles, commercial pressure, safety alerts), this would have been similar in both health areas. In addition, ITS analyses have the advantage that confounding is seldom a problem, since population characteristics (structure by age, sex, educational level, and disease prevalence) tend to change gradually over an extended period of time [48, 49].

In some cases, the intervention and control groups are not perfectly parallel in the pre-intervention period. Here, the data of other potential control groups did not serve as a comparator for our study, in that they did not have the drug which was withdrawn and caused the change in the formulary. To assess the influence of the control group on the results, we conducted a sensitivity analysis by applying a classical ITS model (without a control group). The results were found to be very similar, something that goes to reinforce this study’s conclusions.

As in any observational study with drugs, the absolute value of the variables DDD per day-stay and cost per DDD is limited by the characteristics of hospitals, in terms of activity and care provision. However, we believe that the effects on the trend over time in their use can be extrapolated.

Given that the resources of health systems are limited and that pharmaceutical expenditure is a high percentage of their expenditure, hospital drug formularies can be a very useful and effective tool for improving out-of-hospital prescription profiles in an area and can contain the cost increases associated with drug provision. This is especially important when one recalls that the evaluation of a given drug’s removal comes at zero cost to the organisation. This measure can be implemented in any setting that has a hospital drugs formulary. The hospital can therefore become a generator of good prescribing practices and induce a more efficient use of pharmaco-therapeutic resources in its health catchment area.