Opportunities for new services in pharmaceutical care focusing on infectious diseases – from medication adherence to chlamydia testing

Patients suffering from infectious diseases pose a challenge for healthcare systems in developed and developing countries. Two main issues are the rise of ntimicrobial resistance (AMR) and the high burden of sexually transmitted infections (STIs). Global strategies have been drawn up to overcome these challenges, including optimising antibiotic (AB) use and facilitating people's access to information about their STI status. The optimisation of medication use and the contribution to increase the effectiveness of healthcare systems and public health are pharmacists' key roles, which can be accounted for by expanding pharmaceutical care services in this regard. Thus, the goal of this thesis is to identify and elaborate new opportunities for pharmaceutical care services in patients suffering from infectious diseases. To this end, two projects were performed. Project A) covered medication adherence, and project B) addressed sexually transmitted chlamydia infections. The goal was approached by 1) translating the English ABC taxonomy for adherence into French and English, 2)assessing the magnitude of non-adherence to oral ABs, 3) developing and validating a self-report questionnaire to assess medication adherence barriers in patients taking oral ABs, 4) identifying eligible target groups for pharmacy-based chlamydia screening in Switzerland, 5) assessing pharmacists’ facilitators and barriers to STI counselling during emergency contraception (EC) consultations, and 6) nvestigating whether Swiss pharmacists comply with the official EC protocol focusing on the information provided on the risk of contracting STIs. Medication adherence Project A1 was designed to translate the English ABC taxonomy regarding adherence (i.e. seven terms and their corresponding definitions) into French and German. For this purpose, we conducted a Delphi survey with panellists recruited from ESPACOMP – the International Society for Patient Medication Adherence – and first authors of original research articles published in French or German. Consensus was defined according to the acceptance rate as strong consensus (>95%), consensus (>75-95%), and moderate consensus (>50-75%). Three Delphi rounds were needed to reach a consensus on all terms and corresponding definitions. As an example, the preferred term for medication adherence was "adhésion médicamenteuse" (82%) in French and "Medikamentenadhärenz" (88%) in German. A standardised adherence taxonomy for researchers, clinicians and teaching bodies across three languages will harmonise medication adherence research and ultimately facilitate the comparison of future studies in this field. The findings of this project provided a foundation for designing subsequent adherence projects. In the next step of this thesis, we explored the magnitude of non-adherence in patients taking oral ABs (Project A2). A systematic literature review and meta-analysis was performed through searching PubMed and EMBASE for relevant articles. Inclusion criteria were studies published since the year 2000 investigating medication adherence in adult outpatients taking oral ABs for 3 to 30 days, published in English, French, Italian or German. Summary estimates of medication adherence showed that 32% (95%CI: 41%-23%) were non-adherent to prescribed or AB treatment. Differences in study designs,measurement methods, operational definitions and defined thresholds resulted in substantial heterogeneity (I2=98%). Two of five identified adherence enhancing interventions successfully increased adherence rate by providing the exact number of prescribed pills (+26%) and a pharmacistled educational intervention (+14%). However, a summary estimate of 32% non-adherence to oral AB treatment leaves room for improvement to prevent poor clinical outcomes and the risk of antibiotic resistance. Moreover, we hypothesise that most adherence enhancing interventions were unsuccessful because they were not tailored to patients’ needs. These results served as a rationale for Project A3.In Project A3, we developed and validated a self-report questionnaire assessing adherence barriers to AB treatments in outpatients. Modifiable adherence barriers were identified through a systematic literature search and in a focus group discussion with patients. Extracted barriers served as a basis for the development of a 15-item questionnaire called BIOTICA. Adherence experts working in academia and clinical practice assessed the questionnaire's content validity. The construct validity was assessed in a non-interventional, cross-sectional, primary-care validation study. The questionnaire showed good psychometric properties. The construct validation allowed us to shorten the questionnaire from a 15-item version to a 12-item version. The degree of perceived barriers, expressed as a score between 0 and 48 points for the 12-item version, correlated with a medium effect size to the electronically monitored adherence rate (r=-0.31, p=0.01), indicating that the higher the degree of barriers, the lower the adherence rate was. The ROC analysis suggested a cut-off value of 8 points (e.g. two to three barriers) to identify non-adherent patients (sensitivity: 31%, specificity: 75%). Thus, the BIOTICA questionnaire is a reliable and valid tool to pre-emptively assess medication adherence barriers to oral AB treatment in outpatients. Besides, it provides first hints about a patient's risk of being nonadherent. In the future, the BIOTICA questionnaire is a suitable candidate to match barriers with appropriate interventions and to test the questionnaire in a pilot study. Sexually transmitted chlamydia infections This thesis's second project evaluated an additional opportunity for expanding pharmaceutical care services in patients with infectious diseases, that is, pharmacy-based chlamydia screening. Researchers and clinicians saw pharmacy-based chlamydia screening as an appropriate addition to existing sexual and reproductive healthcare services and acceptable for pharmacists and customers. A core element in planning a pharmacy-based chlamydia screening intervention is to identify an eligible target group. Project B1 was designed to identify such an eligible target group for harmacy-based chlamydia screening in Switzerland. To this end, a systematic literature search identified risk groups for chlamydia infections. Results showed that the chlamydia prevalence (range: 0.8%-12.8%) was similar to realities in other high-income countries. Groups with an increased risk for chlamydia infections included undocumented women undergoing voluntary termination of pregnancy (12.8%), anorectal infections of HIV-positive men having sex with men (10.9%), and adult offenders (6.5%). Thus, identified risk groups were difficult to reach through a pharmacy-based chlamydia screening service due to their unique situation within our society. However, evidence gaps concerned other well-defined risk groups, such as EC users. Thus, more studies are needed to determine Swiss EC users' risk for chlamydia infections in order to assess their eligibility as a target group. Moreover, international guidelines recommend assessing all EC users according to their risk for STIs and advising them on appropriate testing and where to access it. An optional counselling point on the Swiss official EC protocol regarding the risk of contracting an STI during unprotected sexual intercourse considers this recommendation. This recommendation served as a rationale for Project B2. In Project B2, we investigated pharmacists’ facilitators and barriers to STI counselling during EC consultation through a focus group discussion. Participating pharmacists (n=12) were experienced in dispensing EC as most of them (67%) conducted between four to eight EC consultations per month. All interviewed pharmacists felt responsible for counselling on STIs during EC consultations. Facilitating factors comprised (i) EC users’ young age, (ii) no contraception used or the use of condoms, (iii) changing sexual partners, and (iv) repeated EC use. Moreover, pharmacists wished to have some STI specific symptoms listed on the official EC protocol to enrich their counselling. Reported facilitating factors are in line with risk factors for chlamydia infections. Thus, we concluded that pharmacists emphasised STI counselling among EC users most at risk for STIs. As a next step, we verified these qualitative findings in a simulated-patient study regarding EC dispensation in 69 Swiss community pharmacies. Project B3 investigated whether Swiss pharmacists complied with the official EC protocol, solved an imaginary EC case correctly, and what kind of information was provided on the risk of STIs. For this purpose, final year female pharmacy students from the University of Basel were trained on an imaginary EC case and visited a community pharmacy each. Findings showed that all pharmacists used an EC protocol and identified the need for EC correctly. However, only more than half (56%) addressed the risk of STIs, mainly by promoting condom use for protection (76%). Thus, there is room for improvement in Swiss pharmacists’ STI counselling skills during EC consultations. Future research should focus on harmonising and tailoring provided information on the risk of STIs to this particular risk group. Whether the suggested amendment of STI specific symptoms to the official EC protocol lead to a harmonisation of provided information,emphasise chlamydia infections and lead to appropriate testing ecommendations is yet to be demonstrated.In conclusion, this thesis presents two new opportunities for novel pharmaceutical care services in patients suffering from infectious diseases, that is, providing a pharmacist-led antibiotic adherence service and pharmacy-based chlamydia screening. To this end, this thesis generated a standardised adherence taxonomy across three languages for clinicians, researchers and teaching bodies with the ultimate goal to harmonise adherence research. Moreover, this thesis showed that non-adherence to oral AB is scarce, making targeted and tailored interventions crucial to impede adverse clinical and economic outcomes. Finally, the created self-report questionnaire to assess adherence barriers to oral AB treatments serves as a sound basis for targeted and tailored primary care interventions. The second opportunity consists of offering a pharmacy-based chlamydia screening service. This thesis concludes that more studies are needed to provide evidence for an eligible target group for pharmacy-based chlamydia screening in Switzerland, such as EC users. Pharmacists are well aware of risk factors for chlamydia infections by emphasising STI counselling in those most at risk. However, only more than half of the pharmacists tested in a simulated patient study addressed the risk for STIs during EC consultations. Future research and practice recommendations encompass the following: First, promoting the use of a standardised adherence taxonomy in French and German by disseminating our research findings in different professional societies' scientific journals. Second, to match oral AB adherence barriers with appropriate interventions and test them in a pilot intervention study. Moreover, the effectiveness,appropriateness, and cost-effectiveness of such an antibiotic adherence service should be tested in order to assess its qualification for remuneration by health insurances. Third, regarding sexual health,future research should assess EC users’ risk for chlamydia infections in order to identify them as a suitable target group for pharmacy-based chlamydia screening. Moreover, pharmacists' knowledge and counselling skills regarding STIs should be addressed in continuous professional education to harmonise and specify provided information on STIs. Altogether, the two identified opportunities for pharmaceutical care services can significantly expand pharmacists’ contribution to increase effectiveness of healthcare systems and public health regarding infectious diseases once they are carefully planned and fully implemented in daily practice.