Pharmacist Compliance With Therapeutic Guidelines on Diagnosis and Treatment Provision

Key Points Question Are therapeutic guidelines effective mechanisms for ensuring compliance in the provision of over-the-counter pharmaceuticals for symptom-based requests and product-based requests in Australian pharmacies? Findings In this quality improvement study using standardized patients in scenarios of requests for emergency hormonal contraception and medication for conjunctivitis, 57.6% of pharmacies followed dispensing behavior compliant with the protocol, while 31.3% involved some form of overtreatment or overselling of medication. There was also evidence of an interaction between sex of the standardized patient and pharmacist. Meaning Given the unintended adverse effects of overtreatment, this study suggests the advisability of regulatory intervention (and further behavioral research) to ensure compliance with professional protocols.


Introduction
Having identified both the overuse and the underuse of drugs as pressing dilemmas in general medical expenditures, medical professionals see the need for wide-ranging solutions to be "a moral imperative and a political duty." 1(p191) In fact, the frequency with which these problems occur across different markets, countries, and health sectors implies a systematic failure in health care delivery, [1][2][3] one whose implications have significant effects for public health policy across the globe. A defining feature of modern health care policy as both governments and individuals face mounting medical expenses is thus the push for more autonomy in self-treatment and management. Consequently, alternative health care professionals, such as highly trained pharmacists, are commonly used to ease pressure on frontline services. 4,5 In fact, community pharmacists, being so highly accessible to the general public, are becoming increasingly more important to frontline health service delivery. 6,7 This shift is driven not only by increased public reliance on self-medication through over-the-counter products 6,8,9 and the rapid growth of pharmaceutical expenditures as a share of total medical outlay, 10 but also by mounting financial pressure on other health services and the underuse of highly trained pharmacists. 4 One core issue in addressing the overtreatment and undertreatment problem is that health care delivery has considerable information asymmetries between expert clinicians who know more about the type of goods or services the patient needs and the patients or customers who know less about the extent or quality of goods available. [11][12][13][14] Because the discovery costs of overtreatment or undertreatment are high, such asymmetry can result in overprovision and underprovision of treatment. The pharmacist environment is unique in health care services in that it offers a single point of advice and medication provision. Patients describe symptoms and identify a need, which is the basis for pharmacists to then provide a diagnosis (within certain guidelines) and determine the appropriate intervention (including physician referral if warranted). The pharmacist as expert therefore provides information that informs and influences the customer's purchasing decision. Yet, according to a recent overview of the related literature, despite improved understanding of the frequency and causes of overuse, the research is poorly coordinated and has yet to answer several core questions pertinent to improving patient care. 15 We therefore conducted a quality improvement study using standardized patients (SPs) and applied 2 different scenarios to assess pharmacy staff compliance with the professional protocols as a clinical benchmark. Research assistants trained as SPs (customers looking for treatments based on the scenario) made more than 230 visits to 205 different pharmacies to collect interaction data. Our research setting was Brisbane, Australia, which has seen major growth in medical costs to both governments and individuals during the past 20 years, with subsidized pharmaceutical expenditures in 2013-2014 exceeding A$10.1 billion (US $7.1 billion), second only to general medical services. During the same period, spending on prescribed medications and over-the-counter medications was A$9.7 billion (US $6.8 billion), 93% of it paid by individuals. 16 In 2014, the market for all prescription and over-the-counter medicines was worth more than A$19.8 billion (US $13.9 billion), which equated to medicines and appropriate advice, 17 the asymmetric information structure could still encourage undertreatment or overtreatment.
The aim of this study was to examine both diagnostic and compliance behavior of pharmacists in the treatment and provision of medication for 2 common scenarios (a request for emergency hormonal contraception [EHC] and treatment for conjunctivitis) using SPs in the actual field.
However, pharmacists are not required to comply with said guidelines as if they are a fixed protocol; rather, they are to be used as a set of clinical practice guidelines to assist in clinical decision-making.

Study Design and Setting
For this quality improvement study, conducted in Brisbane, Australia, between November 23, 2016, and September 28, 2017, we drew on best-practice material from the Therapeutic Guidelines and Australian Medicines Handbook to construct 2 scenarios representing ideal case management. 18,19 These guidelines are developed by expert panels in each subject area together with associated Standards. 20 We outline the case descriptions, SP scenarios, and expected or ideal guideline-based case management in eTable 1 and eTable 2 in the Supplement. The SP scenarios also considered pharmacist sex, type of pharmacy location (strip mall, shopping center, stand-alone, or medical center), and total number of questions asked. For scenario 2, we additionally note whether or not the pharmacist asked key diagnostic questions to identify the proper treatment.
Ethical approval for the study was granted by the Queensland University of Technology University Human Research Ethics Committee on October 4, 2016. The Queensland University of Technology Ethics Committee granted approval for a waiver of consent of study participants prior to data collection because participants were not informed prior to observation so as not to bias (pharmacist) behavior with the knowledge that they were being observed. This method of research is commonly used in the pharmacy profession for quality assurance purposes. In addition, the ethics review approval provisioned that both relevant regulatory bodies (Pharmacy Guild and Pharmaceutical Society of Australia) were sent the study (ex post completion) for dissemination in their regular member bulletins.

Standardized Patients
A total of 34 undergraduate business students between the ages of 19 and 29 years were recruited to act as SPs, all of whom received appropriate training from the clinical scientists in our research team (G.K. and E.T.L.L.) before field data collection began. Pharmacy students were not used because the university's Clinical Sciences Department has a close relationship with community pharmacies, which provide the students with work placements at the end of their first year. These students recruited as SPs were given a uniform script for their allocated scenario and were required to fill out a survey immediately after leaving the pharmacy to avoid any recall biases (see the eAppendix in the Supplement for the survey questionnaire and detailed protocols).

Pharmacy Selection, SP Visits, and Study Size
Because the research university is centrally located in the central business district, with no onsite accommodation on the central business district campus, the students' residential locations were almost random, which allowed their allocation to pharmacies conditional on area of residence (eFigure in the Supplement). Data collection for scenario 1 (EHC) was conducted from November 23 to December 9, 2016. A total of 9 female SPs, assigned to minimize the confounding effects of the

Scenario 1: EHC
At the time of this study, the most widely used and cost-effective form of EHC was a 1.5-mg tablet of levonorgestrel. 1 Although levonorgestrel was originally categorized by the Therapeutic Goods Authority as an S4 (prescription-only) drug, it was downgraded in January 2004 to an S3 (pharmacist-only) medicine to reduce barriers to supply. 21 The efficacy of this synthetic drug, which replicates the natural hormone progesterone and works by interrupting ovulation, 20 depends on the time interval between intercourse and ingestion, with accepted rates of efficacy based on a multicenter double-blind randomized clinical trial by the World Health Organization. 22 Levonorgestrel has a short half-life (eTable 3 in the Supplement), and there is little to no evidence of its effectiveness if it is taken more than 72 hours after unprotected intercourse. 23 Hence, the clinical and therapeutic guidelines for pharmaceutical dispensation of EHC, which are based on observed efficacy levels at relevant time intervals (eTable 3 in the Supplement), restrict levonorgestrel to 1.5 mg administered within 72 hours after unprotected intercourse. 18,19 Provision of this drug after 72 hours is strictly off label (use outside its own stated consumer medicine information) and unapproved by government regulators because of reduced efficacy and because postcoital contraception with higher efficacy rates after 72 hours are available, albeit only as administered or prescribed by a physician. 20 The challenge presented by this scenario is that the diagnosis is uncertain because of a complete lack of physical symptoms and no means of confirming whether an egg has been fertilized and implanted within 3 to 4 days. It is impossible to know whether the patient would have become pregnant if she had not sought treatment, and because the drug is designed to prevent implantation by interrupting ovulation, the intervention must occur before the pregnancy actually begins (ie, preoutcome).
We applied the scenario to 2 cases. In case 1A, EHC was requested when unprotected intercourse happened within less than 24 hours, referred to in the scenario script as "last night." In case 1B, EHC was requested when unprotected intercourse happened more than 72 hours ago, referred to as "probably 3 days ago last night." This latter case creates a dilemma in that following the Australian Medicines Handbook guideline of referral to a general practitioner without EHC provision results in no sale, and thus no revenue, for the pharmacy. In Table 1, we provide a systematic breakdown of compliance between high-quality (fully compliant) and low-quality (inefficient) treatment subject to undertreatment and overtreatment.

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Pharmacist Compliance With Guidelines on Diagnosis and Treatment Provision

Scenario 2: Infective Conjunctivitis
Conjunctivitis, an inflammation or infection of the mucous membrane covering the anterior sclera and inside eyelid, has 2 infectious forms, viral and bacterial, as well as a noninfectious form induced by allergens. Acute conjunctivitis is a relatively common ailment, with an estimated incidence reported in primary care settings of approximately 1.5% to 2% in the developed world. 24 Although viral and bacterial conjunctivitis present with differentiating characteristics (eTable 4 in the Supplement), some studies suggest that pathogenic ambiguity can lead to misdiagnoses in as high as half of all cases, 25 meaning that many patients receive inappropriate treatment. However, the unnecessary provision of antibiotics to individuals with the viral rather than the bacterial form of conjunctivitis adds to the development of antimicrobial resistance from overprescription of antibiotics. In reality, most conjunctivitis cases are self-limiting within 1 to 2 weeks of presentation, with minimal risk of long-term vision loss, 19,26 a spontaneous remission rate that has led to increasing encouragement of a "delayed prescription" or "delayed antibiotic" approach. 25 Because in our scenario the visual signs and symptoms for viral and bacterial conjunctivitis precluded the SPs from requesting treatment for themselves, the SPs requested treatment for a family member or partner. 27 For case 2A, when symptoms indicate bacterial conjunctivitis, the ideal management specified in the guidelines is prescription of a topical ocular antibiotic or, for mild cases, antiseptic eye drops ( Table 2). Ocular lubricants or saline solutions will not treat the infection, although they can relieve some discomfort. Case 2B describes the presentation of viral conjunctivitis for which antiviral drugs are not recommended; rather, treatment is symptomatic and includes saline solution or an ocular lubricant. Diagnostic ambiguity is present because of conspecific symptom overlap between viral conjunctivitis and the most common type of noninfectious conjunctivitis, allergic conjunctivitis, whose incidence is very high. In the empirical analysis, we controlled for the contradistinctive symptoms of itchy or burning eyes and/or a history of allergies by asking the SP (posing as a family member or partner) the following diagnostic questions: "Do they have any allergies?" (with an answer of "No") and "Do they have any other symptoms?" (with an answer of "Yes, they had a cold about a week ago") (eTable 4 in the Supplement).

Outcome Measures
The 2 outcome variables were pharmacy staff providing inefficient treatments (as opposed to full treatment compliance) and overtreatments based on the case management criteria for each scenario and case defined in Table 1 and Table 2. We included the full staff and SP sex interaction in product terms (male/female staff × male/female SP) to understand whether staff sex is associated with SP sex.

Statistical Analysis
Statistical analysis was performed from January 30 to June 21, 2018, and revised in May 2019. Data were analyzed separately for the EHC scenario and for the infective conjunctivitis scenario. A 2-sample test of proportions was used to evaluate the frequency of outcomes between cases, and   (based on a 2-sample, 2-tailed test of proportions; P < .001). Likewise, the differences between the 2 scenarios clearly indicated that the condition's differential aspects are embedded in the interaction.

Characteristics of the Samples
For case 2B, the pharmacist must differentiate between the highly similar presentations of viral conjunctivitis and allergic conjunctivitis, making 2 questions integral to the diagnosis: "Do they have any allergies?" and "Do they have any other medical conditions?" The answers supplied by the SPs    Table 1. (no history of allergies and the patient having had influenza "about 2 weeks ago") point to a high probability of viral conjunctivitis. However, in the cases of compliant behavior recorded (n = 31) for case 2B, only 2 interactions included both these questions, and only 4 included 1 of the questions.

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Assumedly, in this scenario, the similarity of viral conjunctivitis to other topical types, particularly the highly prevalent allergic conjunctivitis, led pharmacists and pharmacist assistants to recommend antihistamines as the primary treatment in 33 of the 70 interactions (47.1%) involving a sale.
However, of the 49 interactions that led to overtreatment, 33 (67.3%) included at least 1 of the critical diagnostic questions compared with only 6 (28.6%) among the 21 compliant interactions.

Sex in Diagnosis and Treatment
From a broader social perspective, it is also important to note the role in patient treatment of behavioral considerations associated with sex (Figure 2), particularly in the case of over-the-counter     Table 3 presents the multivariate analyses. Pharmacies belonging to a banner group were less likely to provide noncompliant treatment or overtreatment in all scenarios (ranging from 14% to 35.3%), while stores with a price match policy were more likely to provide noncompliant treatment or overtreatment, particularly for scenario 1 (ie, 32.6% and 43.4%). Store location was associated with

Discussion
As with any other expert assistance, the unique and often highly pressured frontline health services provided by pharmacists can be influenced by information transfers in social interactions and by the psychology and emotional state of others. The 2 scenarios in this study illustrate this influence through very different yet challenging diagnosis and provision problems in the pharmacy setting. In the EHC case 1B scenario, the provision problem for pharmacy staff, although centered on the customer's physical health, tends to also carry an emotional cost related to the nature of the condition described. The documentation provided by one SP in case 1B provides qualitative insight into such emotional concerns and how they color motivations: "The pharmacist was initially not going to supply it [EHC] because of the time elapsed; however, after I said I didn't mind, whatever they recommended, they then sold it to me because it was a Friday and she was worried I would not be able to get to the GP [general practitioner]." Nonetheless, in our sample, a sale being made in this case is not likely to be conditional on the presentation occurring on or near the weekend (ie, Friday) when general practitioners are less available and time-sensitive considerations increase. Rather, over-the-counter EHC provision to women by pharmacy experts comes not only with an evaluation dilemma tied to duration since intercourse but, to a lesser extent, with some level of empathy and emotional support in its provision to the customer. This emotional influence may create complications in effective provision. Although there can be no doubt that pharmaceutical provision encompasses a level of empathy and understanding for patients and their medical issues or health, this study provides a very unique SP scenario of reproductive health unlike any previous recent SP studies, to our knowledge. 27,28 In our infective conjunctivitis scenario, pharmacists faced a different issue in efficient provision, that of effective diagnosis. Because the focal point of any symptom-based request is an expert's ability to both listen and ask the right questions, the scripts provided for cases A and B in this scenario were carefully crafted to facilitate the correct diagnosis of the condition described. Hence, the high prevalence of inefficient provision in our sample highlights the information asymmetries in the communication process between the expert clinician and the patient. Such findings align with previous research in that information asymmetry and any subsequent overtreatment can often be

Limitations
There are 4 main limitations to this study. First, the scenarios selected may not be generalized to the provision of other types of over-the-counter medication. Standardized patients were university undergraduate students from Queensland University of Technology recruited for this study, so inferences drawn may not represent the interactions with other members of the population (eg, different age cohorts). Second, the frequency of noncompliant treatment may be influenced by seasonality or demand (eg, influenza season), which is not well accounted for in our study because data were collected during a short period of time (a few weeks). In particular, research has shown that demand for EHC is substantially higher during weekends, the summer holiday, and major festivals, which is likely the result of increased (unsafe) sexual activities. 29 Although all data collection for scenario 1 was conducted within the Queensland school term with no major festival, we observed an association between the weekend effect and noncompliant behavior. Third, the present study did not capture comparative data on patient-physician interaction and compliance behavior.
It is unclear if, for example, overuse of EHC by pharmacists is simply a supply response to market forces imposed by physician behavior. Fourth, it must be noted that there is a gamut of external information (eg, aesthetic, emotive, or contextual factors) involved in the pharmacist-patient interaction that simply cannot all be captured entirely for the purposes of such quality improvement studies.

Conclusions
As the most readily available frontline health service to the public, pharmacies have begun playing a pivotal role in consumer health needs, prompting the Pharmaceutical Society of Australia in 2016 to argue that these highly skilled but underused professionals should play a role in reducing the burden of increasing health costs across the sector. 30 Understanding the interplay of the myriad factors relevant in diagnosis and treatment provision in this setting is thus critical to ensuring effective and efficient outcomes for all parties as the pharmacy market moves forward. However, this study's reliance on markup value restricted our ability to analyze firm-size costs. Future studies may thus seek access to more accurate data on this factor to provide a more robust analysis.