Our research revealed that pharmacist interventions could significantly reduced the percentage of irrational outpatient prescriptions, and this randomly sampled pharmacist interventions had positive economic benefits. Our research has implications for clinical practice and future research, particularly with respect to the emerging role that pharmacists have played in rational drug use surveillance in outpatients.
Many studies have shown the efficacy of pharmacist intervention in optimizing inpatient prescribing practices [22,23,24,25], but few studies have evaluated the issue in outpatients. Therefore, our study focused on the effectiveness of pharmacist intervention in outpatients. Some advantages of outpatient intervention exist in our hospital. First, the number of outpatients in our hospital was large, confirming that we had a sufficient sample size. Second, the doctors in the outpatient department changed little every year in our hospital. Third, self-payment expenditures were paid to the hospital before the medication was dispensed to the patient. Insurance expenditures and public expenditures were paid by insurance companies and the government on a monthly basis. These advantages made it possible to evaluate the clinical and economic impacts of pharmacist interventions on outpatient prescriptions. In our study, the inappropriate rate of outpatient prescriptions decreased from 12.60 to 1.22% due to pharmacist interventions from 2011 to 2016 (Fig. 1B). The results agreed with those of previous studies in pediatric outpatients , geriatric outpatients , emergency outpatients , outpatients receiving oral chemotherapy [11, 12] and those with heart failure .
Randomly sampled prescriptions could well represent the overall inappropriate situation for all prescriptions. It has been reported that the irrational incidence of prescriptions or medication orders was estimated to be 1.59–15.7% with physician-pharmacist team work [24, 26,27,28,29]. In our study, the inappropriate rate of sampled prescription was 1.22–12.60% in 2011–2016 (Fig. 1B).
The effectiveness of randomly sampled pharmacist intervention in our study was not much different from that of overall pharmacist intervention. The recently reported incidence of pharmacist intervention in the CPOE system ranged from 0.5 to 4.8% [28,29,30,31]. Chappuy M et al...  reviewed the outpatient prescriptions of hospital drug sales services in a French university hospital, and 22,279 prescriptions were reviewed over a 1-year period with 247 pharmaceutical interventions (1.1%). Bedouch P et al  reported that the incidence of on-ward pharmacist interventions was 15.7% with acceptance of 79.2%. Hence, a rate of 3.26% IPs persisted after the pharmacist intervention. In our study, the inappropriate rate was decreased to as low as 1.22% over the 6-year pharmacist intervention (Fig. 1). The randomly sampled pharmacist intervention had similar effect as the fully sampled or on-ward pharmacist intervention.
Though pharmacist intervention could reduce IPs in all departments, it seemed that pharmacist intervention might be most needed in Department of Surgery. The inappropriate percentage in this department was highest in 2011, and reduced significantly by the pharmacist intervention (Fig. 2). However, the inappropriate percentage in this department was still somewhat higher than other department in 2016. The higher inappropriate percentage may because of the low level of standardization of medication use in this department. There are little guidelines or expert consensuses in surgical disease, and guidelines about medication use in Department of Surgery have not issued in our hospital. Pharmacists should pay more attention on rational use of medication in Department of Surgery. The inappropriate percentage in the Department of Oncology was always lower than the other departments (Fig. 2). There are many recognized guidelines in cancer therapy such as National Comprehensive Cancer Network guidelines, ASCO guidelines, ESMO guidelines CSCO guidelines and so on. According to these guidelines in treatment of disease, the pharmacists had issued a guideline for the rational use of anticancer drugs in 2011 in our hospital. This might an explanation of the lower inappropriate percentage in Department of Oncology.
Though pharmacist intervention could reduce IPs in all categories, it seemed that pharmacist intervention might be most needed in Category 1 (medications with no medical indication). Category 1 (medications with no medical indication) was always the majority inappropriate type, although its percentage decreased annually from 2011 to 2015 (Fig. 3). Another Chinese hospital also reported that 48.54% of urological inpatients undergoing clean or clean-contaminated operations had non-indicated medications before pharmacist interventions . Pharmacists should pay more attention on the irrational issue of medications with no medical indication.
Category 3 (inappropriate choice of medication) decreased rapidly from 2011 to 2016, and became a minority of inappropriate types in 2015. It has reported that most acceptable pharmacist intervention is “inappropriate choices of medications” . As demonstrated by Bedouch P et al. , physicians’ acceptance of “inappropriate choices of medications” was 84.1%, which was higher than the average level (79.2%) of pharmacist interventions. This type of irrational issue can improved significantly and quickly by the pharmacist interventions.
Studies of the economic impacts of pharmacist interventions have been limited and have been mostly about inpatients [15, 16, 27, 32,33,34]. Besides the cost savings, the benefit includes cost avoidance  and ultimate improvement. Cost avoidance was defined as the potential economic benefit obtained from interventions that could have prevented ADEs, determined by the total number of intervention cases multiplied by the probability of each potential ADE and the costs associated with ADEs . Ultimate improvement was defined as the practical improvement in health outcome and quality of life. It is very difficult to estimate the cost avoidance and ultimate improvement in outpatients. In our study, benefits included only cost savings, the sum of the expenses for all inappropriate issues. Hence, the benefit of the pharmacist intervention was underestimated in our study.
In our study, the benefit-to-cost ratios of pharmacist interventions were always more than 1, which showed positive economic effect (Table 3). The cost-effective results in our study were not much different from those with reported on-ward pharmacist interventions. Han JM et al.......  reported that the cost-benefit ratio was 3.64 with pharmacist interventions for large-volume ambulatory-based chemotherapy. Zhang HX et al  reported that the cost-benefit ratio was approximately 18.79 with pharmacist interventions for prophylactic antibiotic use in surgical patients undergoing clean or clean-contaminated operations. Ah YM et al  reported that the cost-benefit ratio was 3.8 with pharmacist interventions as members of a liver transplant team for hospitalized liver recipients. Rychlíčková J et al  reported that the cost-benefit ratio was 3 with clinical pharmacist interventions in the Czech Republic.
The benefit-cost ratio drops from 8.73 in 2011 to 1.14 in 2016, and it shows the great improvement of reduction of IP mainly due to the interventions and education of pharmacists. For example, if levofloxacin was prescripted for the treatment of mammitis, it was judged as IP by the pharmacist, and the issue was communicated to the prescriber via telephone. In the beginning of next month, educations about antibacterial treatment of mammitis were made to all breast surgeons and gynecologists in order to avoid similar IPs. Intervention and education both played an important role in reducing the number and cost of IPs.
Pharmacist intervention was especially important for prescriptions at public payments. The irrational rates and benefit-to-cost ratios of prescriptions at public payments were highest in our study (Table 4). Prescriptions with public payments are totally paid by the government, and they constitute a large proportion of public health expenditures. Prescriptions with insurance payments are supervised by the insurance companies, while prescriptions with public payments aren’t supervised by other organizations. Thus, pharmacist supervision of prescriptions with public payments is especially necessary. There were some limitations of this study. First, this intervention study was performed on the basis of a retrospective design and therefore was less convincing than a prospective, controlled study design. Second, potentially IPs which rejected by doctors were not judged as IPs, which could have led to underestimation of the benefit. Third, the favorable results obtained could not be attributed solely to the pharmacist interventions; therefore, a larger sample size and more rigorous design should be employed to evaluate this promising intervention.
The significance of this study lies in the evaluation of interventions performed routinely over a long period of time by pharmacists in a system in which the role of the pharmacist is stable. This system is the basis for expanding the activities of pharmacists, as well as for the possibility of having their work remunerated by the health care insurance system. Despite its limitations, the economic analysis supported these claims.