Objective Measures Of Adherence Research Articles

WS16.4 Objective measurement of adherence to airway clearance in cystic fibrosis

WS16.4 Objective measurement of adherence to airway clearance in cystic fibrosis

Objective Measurement of Adherence to Out-Patient Airway Clearance Therapy by High-Frequency Chest Wall Compression in Cystic Fibrosis.

Objective measures of adherence to high-frequency chest wall compression (HFCWC), a form of airway clearance therapy for patients with cystic fibrosis, are lacking. We used a novel electronic monitoring device integrated into an HFCWC vest to measure adherence compared with self-reported adherence. We determined factors that influenced adherence and how adherence correlated with baseline pulmonary function and pulmonary exacerbations. Data were collected by direct measurement of date, time of day, and duration of HFCWC use to determine the number of daily treatments and daily duration of treatments. Chart review provided prescribed airway clearance therapy treatment and demographic and clinical information. Subject and caregiver report of the daily number of airway clearance therapy treatments was obtained by telephone interviews. Analysis used 2-sample and paired t test, analysis of variance, and linear regression. Average adherence was 69%. Adherence was highest in children (82%, P = .02) and those receiving assistance with treatment (82%, P < .001). Subjects overestimated therapy duration from a mean ± SD of 127 ± 169% by adults to 19.2 ± 26.3% by parents or guardians of children. Average adherence decreased with increasing prescribed therapy time (P = .02). Average daily therapy time and adherence had significant positive associations with baseline FEV1 percent of predicted (P = .02 and P = .02, respectively) and negative associations with pulmonary exacerbations during the pre-study period and at baseline (P = .044 and P = .02, respectively). Greater adherence to HFCWC measured directly by a novel recorder was associated with better baseline pulmonary function and fewer exacerbations in the pre-study and baseline period. Adherence decreased with age and prescribed therapy time and increased with therapy assistance. Self-report overestimation is large and thus not an accurate measure of adherence.

Interventions to improve adherence to inhaled steroids for asthma.

Interventions to improve adherence to inhaled steroids for asthma.

Comparison of six methods to estimate adherence in an ART-na\xefve cohort in a resource-poor setting: which best predicts virological and resistance outcomes?

BackgroundIncomplete adherence to antiretroviral therapy (ART) results in virologic failure and resistance. It remains unclear which adherence measure best predicts these outcomes. We compared six patient-reported and objective adherence measures in one ART-naïve cohort in South Africa.MethodsWe recruited 230 participants from a community ART clinic and prospectively collected demographic data, CD4 count and HIV-RNA at weeks 0, 16 and 48. We quantified adherence using 3-day self-report (SR), clinic-based pill count (CPC), average adherence by pharmacy refill (PR-average), calculation of medication-free days (PR-gaps), efavirenz therapeutic drug monitoring (TDM) and an electronic adherence monitoring device (EAMD). Associations between adherence measures and virologic and genotypic outcomes were modelled using logistic regression, with the area under the curve (AUC) from the receiver operator characteristic (ROC) analyses derived to assess performance of adherence measures in predicting outcomes.ResultsAt week 48 median (IQR) adherence was: SR 100% (100–100), CPC 100% (95–107), PR-average 103% (95–105), PR-gaps 100% (95–100) and EAMD 86% (59–94), and efavirenz concentrations were therapeutic (>1 mg/L) in 92%. EAMD, PR-average, PR-gaps and CPC best predicted virological outcome at week 48 with AUC ROC of 0.73 (95% CI 0.61–0.83), 0.73 (95% CI 0.61–0.85), 0.72 (95% CI 0.59–0.84) and 0.64 (95% CI 0.52–0.76) respectively. EAMD, PR-gaps and PR-average were highly predictive of detection of resistance mutations at week 48, with AUC ROC of 0.92 (95% CI 0.87–0.97), 0.86 (0.67–1.0) and 0.83 (95% CI 0.65–1.0) respectively. SR and TDM were poorly predictive of outcomes at week 48.ConclusionEAMD and both PR measures predicted resistance and virological failure similarly. Pharmacy refill data is a pragmatic adherence measure in resource-limited settings where electronic monitoring is unavailable.Trial registration The trial was retrospectively registered in the Pan African Clinical Trials Registry, number PACTR201311000641402, on the 13 Sep 2013 (www.pactr.org). The first participant was enrolled on the 12th July 2012. The last patient last visit (week 48) was 15 April 2014

Impact of Medication Adherence on the Effect of Renal Denervation: The SYMPATHY Trial.

URL: http://www.clinicaltrials.gov. Unique identifier: NCT01850901.

Financial Incentives for Adherence to Hepatitis C Virus Clinical Care and Treatment: A Randomized Trial of Two Strategies.

BackgroundAlthough rates of sustained virologic response (SVR) after hepatitis C virus (HCV) treatment with direct-acting antivirals (DAAs) surpass 90% in trials and some more “real world” settings, some patients, such as those with substance use disorders, will be challenged to adhere to HCV care.MethodsTo assess the feasibility of 2 strategies for financially incentivizing adherence to HCV care, patients with a substance use history prescribed 12 weeks of a sofosbuvir-containing regimen were randomized to either fixed or lottery-based monetary incentives for attending clinic appointments, pill count adherence >90%, and SVR achievement. Electronic medication monitoring provided an objective measure of DAA adherence.ResultsFifty-nine participants were randomized to the lottery (n = 31) or fixed-incentive (n = 28) arms. All 31 (100%) in the lottery arm and 24 of 28 (86%) in the fixed arm completed 12 weeks of therapy. By intent-to-treat, 93% in the lottery arm and 92% in the fixed arm achieved SVR (estimated difference: 0.5%; 95% confidence interval, −17.5 to 18.8). Overall, 92% of scheduled visits were attended without significant differences between arms. The mean adherence ratio (days with ≥1 bottle opening:monitored days) was 0.91 for lottery and 0.92 for fixed arms.ConclusionsIn this pilot, fixed- and lottery-based financial incentives were successfully implemented and accepted by patients with a substance use history. High levels of HCV therapy and care adherence, as well as rates of SVR, were observed. Financial incentives may be useful to support treatment adherence in patients with substance use disorders and should be tested in a larger, randomized, controlled trial.

Dispatch guideline adherence and response interval-a study of emergency medical calls in Norway.

BackgroundThe Emergency Medical Communication Centre (EMCC) operators in Norway report using the Norwegian Index for Medical Emergency Assistance (Index), a criteria-based dispatch guideline, in about 75 % of medical emergency calls. The main purpose of a dispatch guideline is to assist the operator in securing a correct response as quickly as possible. The effect of using the guideline on EMCC response interval is as yet unknown. We wanted to ascertain an objective measure of guideline adherence, and explore a possible effect on emergency medical dispatch (EMD) response interval.MethodsObservational cross-sectional study based on digital telephone recordings and EMCC records; 299 random calls ending in acute and urgent responses from seven strategically selected EMCCs were included. Ability to confirm location and patient consciousness within an acceptable time interval and structural use of criteria cards were indicators used to create an overall guideline adherence variable. We then explored the relationship between different levels of guideline adherence and EMD response interval.ResultsThe overall guideline adherence was 80 %. Location and patient consciousness were confirmed within 1 min in 83 % of the calls. The criteria cards were used systematically as intended in 64 % of the cases. Total median response interval was 2:28, with 2:01 for acute calls and 4:10 for urgent calls (p < 0.0005). Lower guideline adherence was associated with higher EMD response interval (p < 0.0005).ConclusionThe measured guideline adherence was higher than previously reported by the operators themselves. Patient consciousness was rapidly confirmed in the majority of cases. Failure to use Index criteria as intended result in delayed ambulance dispatch and a potential risk of undertriage.Electronic supplementary materialThe online version of this article (doi:10.1186/s12873-016-0105-2) contains supplementary material, which is available to authorized users.

Integrated Delivery of Antiretroviral Treatment and Pre-exposure Prophylaxis to HIV-1-Serodiscordant Couples: A Prospective Implementation Study in Kenya and Uganda.

BackgroundAntiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings.Methods and FindingsBetween November 5, 2012, and January 5, 2015, we enrolled and followed 1,013 heterosexual HIV-1-serodiscordant couples in Kenya and Uganda in a prospective implementation study. ART and PrEP were offered through a pragmatic strategy, with ART promoted for all couples and PrEP offered until 6 mo after ART initiation by the HIV-1 infected partner, permitting time to achieve virologic suppression. One thousand thirteen couples were enrolled, 78% of partnerships initiated ART, and 97% used PrEP, during a median follow-up of 0.9 years. Objective measures of adherence to both prevention strategies demonstrated high use (≥85%). Given the low HIV-1 incidence observed in the study, an additional analysis was added to compare observed incidence to incidence estimated under a simulated counterfactual model constructed using data from a prior prospective study of HIV-1-serodiscordant couples. Counterfactual simulations predicted 39.7 HIV-1 infections would be expected in the population at an incidence of 5.2 per 100 person-years (95% CI 3.7–6.9). However, only two incident HIV-1 infections were observed, at an incidence of 0.2 per 100 person-years (95% CI 0.0–0.9, p < 0.0001 versus predicted). The use of a non-concurrent comparison of HIV-1 incidence is a potential limitation of this approach; however, it would not have been ethical to enroll a contemporaneous population not provided access to ART and PrEP.ConclusionsIntegrated delivery of time-limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of <0.5% per year compared to an expected incidence of >5% per year.

A Web-Based and Mobile Health Social Support Intervention to Promote Adherence to Inhaled Asthma Medications: Randomized Controlled Trial.

BackgroundOnline communities hold great potential as interventions for health, particularly for the management of chronic illness. The social support that online communities can provide has been associated with positive treatment outcomes, including medication adherence. There are few studies that have attempted to assess whether membership of an online community improves health outcomes using rigorous designs.ObjectiveOur objective was to conduct a rigorous proof-of-concept randomized controlled trial of an online community intervention for improving adherence to asthma medicine.MethodsThis 9-week intervention included a sample of asthmatic adults from the United Kingdom who were prescribed an inhaled corticosteroid preventer. Participants were recruited via email and randomized to either an “online community” or “no online community” (diary) condition. After each instance of preventer use, participants (N=216) were required to report the number of doses of medication taken in a short post. Those randomized to the online community condition (n=99) could read the posts of other community members, reply, and create their own posts. Participants randomized to the no online community condition (n=117) also posted their medication use, but could not read others’ posts. The main outcome measures were self-reported medication adherence at baseline and follow-up (9 weeks postbaseline) and an objective measure of adherence to the intervention (visits to site).ResultsIn all, 103 participants completed the study (intervention: 37.8%, 39/99; control: 62.2%, 64/117). MANCOVA of self-reported adherence to asthma preventer medicine at follow-up was not significantly different between conditions in either intention-to-treat (P=.92) or per-protocol (P=.68) analysis. Site use was generally higher in the control compared to intervention conditions.ConclusionsJoining an online community did not improve adherence to preventer medication for asthma patients. Without the encouragement of greater community support or more components to sustain engagement over time, the current findings do not support the use of an online community to improve adherence.ClinicalTrialInternational Standard Randomized Controlled Trial Number (ISRCTN): 29399269; http://www.isrctn.com/ISRCTN29399269/29399269 (Archived by WebCite at http://www.webcitation.org/6fUbEuVoT)

Random lopinavir concentrations predict resistance on lopinavir-based antiretroviral therapy

Considering that most patients who experience virological failure (VF) on lopinavir-based antiretroviral therapy (ART) fail due to poor adherence rather than resistance, an objective adherence measure could limit costs by rationalising the use of genotype antiretroviral resistance testing (GART) in countries with access to third-line ART. A cross-sectional study was conducted in a resource-limited setting at two large clinics in Kwazulu-Natal, South Africa, in patients experiencing VF (HIV-RNA > 1000 copies/mL) on lopinavir-based ART who had undergone GART. Associations between major protease inhibitor (PI) resistance mutations and random plasma lopinavir concentrations were explored. A total of 134 patients, including 31 children, were included in the analysis. The prevalence of patients with major PI resistance mutations was 20.9% (n = 28). A random lopinavir concentration above the recommended minimum trough of 1 µg/mL [adjusted odds ratio (aOR) = 5.81, 95% confidence interval (CI) 2.04–16.50; P = 0.001] and male sex (aOR = 3.19, 95% CI 1.22–8.33; P = 0.018) were predictive of the presence of at least one major PI resistance mutation. Random lopinavir concentrations of <1 µg/mL had a negative predictive value of 91% for major PI resistance mutations. Random lopinavir concentrations are strongly associated with the presence of major PI resistance mutations. Access to costly GART in patients experiencing VF on second-line ART could be restricted to patients with lopinavir concentrations above the recommended minimum trough of 1 µg/mL or, in areas where GART is unavailable, could be used as a criterion to empirically switch to third-line ART.

Objective quantification of adherence to prophylaxis in haemophilia patients aged 12 to 25 years and its potential association with bleeding episodes

BackgroundThe treatment of choice for patients with severe haemophilia is prophylaxis with clotting factor. Effective prophylaxis requires optimal adherence. Most published studies are based on surveys and interviews with patients or their parents. However, studies based on objective measurements of adherence are few and inconclusive. ObjectiveThe main purpose of this study was to assess adherence to prophylaxis using an objective method in patients with haemophilia aged 12 to 25years as well as to assess its potential association with bleeding episodes. Secondary objectives included comparing objective and subjective adherence (questionnaire) and identifying factors potentially associated with treatment adherence. MethodsA retrospective observational study was designed to collect data on treatment adherence and clinical course of patients in 2013. The study included haemophilia patients on prophylaxis with clotting factor concentrate; the age range was 12 to 25years.Objective adherence to treatment was measured through pharmacy dispensing records. Dispensing dates within 2013 were used for calculation. Adherence (%) was calculated by dividing the total number of International Units (IU) of factor dispensed by the total estimated number of IU and multiplying by 100.Subjective adherence was measured using an ad hoc questionnaire which was completed by the patient. The number of bleeding episodes (joint, muscle and others) was obtained from interviews with the patient at the consultation with the pharmacist and was subsequently confirmed with the patient's clinical history. Other parameters were also evaluated. ResultsWe included 52 patients in the study. Average adherence of patients resulting from the analysing of dispensing records was 85.72 (SD=23.76%). The global average of bleeding episodes was 2.2 (SD=2.69). 32.6% (seventeen) patients presented with at least one joint bleeding episode versus 67.3% (thirty five) who showed no joint bleeding episodes. Likewise, only 10% (five) patients presented with one muscle bleeding episode. Even though a significant association between the rate of objective adherence and the number of bleeding episodes was not observed, a higher number of hemarthrosis was observed in less-adherent patients.Subjective adherence perceived by patients as reported by the questionnaire showed that 36 (83.7%) of the 43 patients who completed the questionnaire considered their adherence as good, whereas 7 (16.3%) of the 43 patients considered it as fair. A statistically significant relationship was found between objective adherence expressed as a percentage using dispensing records, and subjective adherence perceived by the patient (p=0.004). The other parameters evaluated were not associated with adherence to prophylaxis. ConclusionsMeasuring objective adherence using pharmacy dispensing records is a simple and useful tool. No significant correlation was found between the rate of objective adherence observed and the number of bleeding episodes; however, a higher number of hemarthrosis was observed in less-adherent patients.

Reporting of Adherence in the VOICE Trial: Did Disclosure of Product Nonuse Increase at the Termination Visit?

VOICE-a phase 2B, placebo-controlled, randomized trial testing daily use of an antiretroviral tablet (tenofovir or Truvada) or daily use of tenofovir gel in 5029 women from South Africa, Uganda, and Zimbabwe-found none of the drug regimens effective in reducing HIV-1 acquisition in the intent-to-treat analysis. More than half of women assigned to active products in a case cohort sample had no drug detected in any plasma specimens tested during the trial. Yet, in response to questions asked of participants during the trial, ≥90% of doses were reportedly taken. To explore factors associated with low adherence, a behavioral termination visit questionnaire was developed after early closure of the oral tenofovir and vaginal gel arms. We hypothesized that participants would be more forthcoming about nonuse after they exited the trial than during monthly/quarterly follow-up visits. Comparison of adherence reporting at routine follow-up visits with reporting at trial termination, however, indicates that disclosure of product nonadherence did not increase at the termination visit as anticipated. In resource-limited settings where women value the ancillary benefits provided by trial participation and are concerned that disclosure of nonuse may jeopardize trial participation, objective measures of adherence may yield more meaningful data regarding the inability or reluctance to use than measures of product use derived from self-report.

Current concepts for PrEP adherence in the PrEP revolution: from clinical trials to routine practice.

The review describes the current understanding of adherence to oral preexposure prophylaxis (PrEP), methods for adherence measurement, approaches to supporting PrEP adherence, and guidance for defining PrEP adherence goals within the larger context of HIV prevention. PrEP adherence has generally been higher in recent trials, open-label extensions, and demonstration projects compared with the initial clinical trials; potential explanations include known PrEP efficacy and different motivations to take PrEP. Recent studies have explored adherence monitoring through electronic pill containers, short message service (SMS), and drug concentrations in hair and dried blood spots. The few PrEP adherence interventions developed to date include combinations of enhanced counseling, feedback of objective adherence measurement, and SMS. Conceptualization of PrEP adherence is evolving. The goal is not 100% adherence indefinitely, as it was in clinical trials. PrEP adherence should be defined with respect to HIV exposure, which varies over time by sexual behavior and use of other prevention strategies. PrEP adherence beyond clinical trials has generally been high enough to achieve reliable HIV prevention. Future efforts to measure and support PrEP adherence should focus on the context of risk for HIV acquisition, accounting for dynamic behaviors and choices among HIV prevention options.

Medication beliefs and structural barriers to treatment adherence among people living with HIV infection

Background: People living in poverty face multiple structural challenges to medication adherence including lack of transportation, inadequate housing and food insecurity. The degree to which individuals’ motivations to remain adherent may overcome structural barriers has received limited attention.Purpose: To examine whether medication necessity and concerns beliefs predict antiretroviral therapy (ART) adherence over and above structural adherence barriers associated with poverty.Methods: People living with HIV in a southern US city (N = 942) completed computerised interviews, an objective measure of adherence and HIV viral suppression obtained from medical records. Hierarchical logistic regression models were constructed to examine demographic and illness characteristics, structural barriers, mental health, substance use and medication necessity and concerns beliefs as predictors of ART adherence.Results: In multivariable models, current drug use and medication necessity and concerns beliefs predicted treatment adherence over and above demographic, health, mental health and structural factors.Conclusions: Medication beliefs are proximal and powerful motivating factors that predict adherence. Adherence interventions should directly address medication beliefs in developing strategies to manage barriers facing people with HIV living in poverty.

Defining success with HIV pre-exposure prophylaxis: a prevention-effective adherence paradigm.

Clinical trial data have shown that oral pre-exposure prophylaxis (PrEP) is efficacious when taken as prescribed; however, PrEP adherence is complex and must be understood within the context of variable risk for HIV infection and use of other HIV prevention methods. Different levels of adherence may be needed in different populations to achieve HIV prevention, and the optimal methods for achieving the necessary adherence for both individual and public health benefits are unknown. Guidance for PrEP use must consider these questions to determine the success of PrEP-based HIV prevention programs. In this article, we propose a new paradigm for understanding and measuring PrEP adherence, termed prevention-effective adherence, which incorporates dynamic HIV acquisition risk behaviors and the use of HIV alternative prevention strategies. We discuss the need for daily PrEP use only during periods of risk for HIV exposure, describe key issues for measuring and understanding relevant behaviors, review lessons from another health prevention field (i.e., family planning), and provide guidance for prevention-effective PrEP use. Moreover, we challenge emerging calls for sustained, near perfect PrEP adherence regardless of risk exposure and offer a more practical and public health-focused vision for this prevention intervention.

The development of the ProMAS: a Probabilistic Medication Adherence Scale.

Current self-report medication adherence measures often provide heavily skewed results with limited variance, suggesting that most participants are highly adherent. This contrasts with findings from objective adherence measures. We argue that one of the main limitations of these self-report measures is the limited range covered by the behaviors assessed. That is, the items do not match the adherence behaviors that people perform, resulting in a ceiling effect. In this paper, we present a new self-reported medication adherence scale based on the Rasch model approach (the ProMAS), which covers a wide range of adherence behaviors. The ProMAS was tested with 370 elderly receiving medication for chronic conditions. The results indicated that the ProMAS provided adherence scores with sufficient fit to the Rasch model. Furthermore, the ProMAS covered a wider range of adherence behaviors compared to the widely used Medication Adherence Report Scale (MARS) instrument, resulting in more variance and less skewness in adherence scores. We conclude that the ProMAS is more capable of discriminating between people with different adherence rates than the MARS.

The 8-item Morisky Medication Adherence Scale translated in German and validated against objective and subjective polypharmacy adherence measures in cardiovascular patients.

To translate in German the 8-item Morisky Medication Adherence Scale (MMAS-8D). To validate it against objective and subjective measures of adherence in cardiovascular patients with polypharmacy. A standard forward-backward procedure was used to translate the MMAS-8 into German. Validation took place on a convenience sample of ambulatory patients on chronic antiplatelet therapy between June 2010 and June 2011. Objective adherence was obtained from electronically monitored multi-drug punch cards. Internal consistency was assessed using Cronbach's alpha coefficient, construct validity using exploratory factor analyses and correlations between MMAS-8D and related measures. Convergent validity was assessed with a subjective questionnaire about beliefs about medicines (BMQ Specific, two sub-scales). A total of 70 patients were included (mean age 65.7 ± 9.9 years; 31.4% women). The mean score of the MMAS-8D was 7.5 (SD 0.8; range 4.5-8). Moderate internal consistency (alpha = 0.31) was observed due to multidimensionality of the scale. Factor analysis yielded four components that accounted for 71.7% of the total variance. Convergent validity was supported by significant correlations with BMQ Necessity (r = 0.31, P < 0.01), BMQ Concerns (r = -0.16, P < 0.05) and with electronic adherence reports (U-values 44 and 471, P < 0.05). Platelet aggregation values were within therapeutic range for 80% of the patients. Blood values of the antiplatelet agent within therapeutic range were associated with a higher MMAS-8D score (U-value 125, P < 0.05). The German MMAS-8 appears to be a reliable instrument to catch medication adherence in cardiovascular patients. It may be useful in patients with chronic therapy for detecting non-adherence.

An evaluation of the impact of memory and mood on antiepileptic drug adherence

RationaleAntiepileptic drugs are the mainstay of treatment for patients with epilepsy. Adherence to the prescribed regimen is a major factor in achieving a reduced seizure burden, which can decrease morbidity and mortality. Patients with epilepsy oftentimes complain about difficulty with memory. Because little is known about the relationship between memory and mood and adherence, the purpose of this project was to determine the impact of the confounding factors of memory and mood on antiepileptic drug adherence in patients with epilepsy. MethodsOne hundred adult patients with epilepsy were recruited from the outpatient neurology clinic for this cross-sectional study. Patients who met the inclusion criteria completed measures of subjective memory (subset of 6 memory questions from the QOLIE-89) and objective memory (Hopkins Verbal Learning Test — Revised), subjective adherence (Morisky scale) and objective adherence (medication possession ratio), and mood (Neurological Disorders Depression Inventory for Epilepsy). Refill records from each patient's community pharmacy were used to objectively assess adherence. Medication possession ratios were calculated based on the antiepileptic drug refill records over the previous 6months. Patients were considered adherent if their MPR was >80%. ResultsWomen made up the majority of the sample (n=59), and, on average, patients had been living with epilepsy for nearly 20years. Approximately 40% of the sample were on antiepileptic drug monotherapy; most patients (>70%) took their antiepileptic drugs twice daily, and the mean number of total medications was 4.25±2.98. Based on the objective measure of adherence, 35% of the patients were nonadherent. Patients self-reported better adherence than what was objectively measured. Only the retention metric of the objective memory measure differentiated adherent patients from nonadherent patients. Patients in the adherent group had significantly lower depression scores (indicating better mood) compared with those in the nonadherent group (p=0.04). ConclusionsObjective memory measures were not robustly correlated with adherence. However, we observed that patients with higher depressed mood scores were more likely to be nonadherent. By targeting patients with epilepsy and comorbid depression, practitioners may identify patients at greatest risk of nonadherence and subsequent harm.

Medication Adherence Measures: An Overview.

WHO reported that adherence among patients with chronic diseases averages only 50% in developed countries. This is recognized as a significant public health issue, since medication nonadherence leads to poor health outcomes and increased healthcare costs. Improving medication adherence is, therefore, crucial and revealed on many studies, suggesting interventions can improve medication adherence. One significant aspect of the strategies to improve medication adherence is to understand its magnitude. However, there is a lack of general guidance for researchers and healthcare professionals to choose the appropriate tools that can explore the extent of medication adherence and the reasons behind this problem in order to orchestrate subsequent interventions. This paper reviews both subjective and objective medication adherence measures, including direct measures, those involving secondary database analysis, electronic medication packaging (EMP) devices, pill count, and clinician assessments and self-report. Subjective measures generally provide explanations for patient's nonadherence whereas objective measures contribute to a more precise record of patient's medication-taking behavior. While choosing a suitable approach, researchers and healthcare professionals should balance the reliability and practicality, especially cost effectiveness, for their purpose. Meanwhile, because a perfect measure does not exist, a multimeasure approach seems to be the best solution currently.

Development of a Composite Measure of Product Adherence, Protocol Compliance, and Semen Exposure Using DNA and Protein Biomarkers for Topical HIV Prevention Studies

BackgroundPoor and inconsistent use of study products has hindered clinical HIV prevention studies. It is important to be able to monitor product adherence and protocol compliance in order to determine microbicide efficacy and safety more accurately. Current methods for monitoring adherence are subjective, non-specific, or invasive. Herein, we present a composite, objective measure of product adherence and protocol compliance to assess vaginal insertion, semen exposure and drug expulsion utilizing DNA, protein, and drug isolated directly from returned, vaginally used gel applicators.MethodsDNA, vaginal cells, and residual tenofovir were isolated from vaginally inserted applicators. Vaginal and semen biomarkers were amplified using a multiplex PCR to determine vaginal insertion. Vaginal cells were fixed followed by cytokeratin 4 immunocytochemistry to confirm DNA assessment of vaginal insertion. Tenofovir was extracted and quantitated through LC-MS/MS.ResultsDNA isolated from vaginally inserted applicators were positive for vaginal bacteria DNA and the control eukaryotic gene, amelogenin, while manually handled, “sham”, applicators were negative for both. Semen exposure was independently determined by simultaneous amplification of one or both Y-chromosomal genes, SRY and TSPY4. Vaginal insertion determination by DNA analysis was further confirmed by positive cytokeratin 4 (CK4) immunocytochemistry of vaginal cells remaining on the gel applicators. On the contrary, sham applicators provided very few cells when swabbed, and they were all negative for CK4. CK4 was not found in epidermal cells from the hand. Drug expulsion was detected through quantitation of residual gel present on the surface of returned applicators. Sham applicators had no detectable tenofovir.ConclusionUtilizing a composite, triple marker based panel of DNA, protein, and drug present on the surface of returned vaginal gel applicators, it is possible to determine, objectively and non-invasively, product adherence, protocol compliance, and semen exposure in microbicide trials.