Rosirene Paczkowski

Comprehensive review of factors implicated in the heterogeneity of response in depression

Heterogeneity in overall response and outcomes to pharmacological treatment has been reported in several depression studies but with few sources that integrate these results. The goal of this study was to review the literature and attempt to identify nongenetic factors potentially predictive of overall response to depression treatments.

Heterogeneity of Response to Biologic Treatment: Perspective for Psoriasis

Psoriasis treatment responses are affected by patient characteristics. However, the literature does not contain reviews of factors that affect the response to biologic therapies. We therefore performed a comprehensive literature search to identify papers describing demographic, lifestyle, and clinical factors associated with response to biologic drug therapy in psoriatic patients. We found that age, gender, ethnicity, alcohol consumption, smoking, geographic location, age at diagnosis, duration and severity of psoriasis, and baseline C-reactive protein levels did not consistently affect response to biologic psoriasis therapy. However, increased body mass index (BMI) appears to adversely affect responses. It might therefore be valuable to include BMI as a stratification variable in future studies of psoriasis therapies and to consider a patients weight or BMI when selecting a systemic psoriasis treatment.

A review of treatment response in type 2 diabetes: assessing the role of patient heterogeneity.

The response to treatment for type 2 diabetes typically varies among individuals within a study population. This variation is known as heterogeneity of treatment response. We conducted a comprehensive literature review to identify factors that account for heterogeneity of treatment response in patients treated for type 2 diabetes. Three databases (PubMed, EMBASE and Cochrane Library) were searched for articles published in the last 10 years describing investigations of factors associated with treatment response and outcomes among people with type 2 diabetes receiving pharmacological treatment. Of the 43 articles extracted and summarized, 35 (81%) discussed clinical factors, 31 (72%) described sociodemographic factors and 17 (40%) reported on comorbidity or behavioural factors. Clinical factors identified included baseline glycated hemoglobin A1c or fasting plasma glucose (FPG) levels, insulin response or sensitivity, C‐peptide, body composition, adipose tissue proteins, lipid profile, plasma albumin levels and duration of disease or insulin treatment. Other factors identified included age, sex, race, socioeconomic status and comorbidities. This review identified the following research gaps: use of multiple definitions for response, few patient‐reported measures and lack of evidence regarding whether factors were associated with treatment response for only specific medications or across pharmacological therapies. Furthermore, identification of factors associated with type 2 diabetes treatment response was generally a secondary objective in the research reviewed. Understanding which patient subgroups are more likely to respond to treatment and identifying factors associated with response may result in targeted treatment decisions and alter the interpretation of efficacy or effectiveness of results. In conclusion, accounting for these factors in clinical trials and when making clinical treatment decisions may improve therapy selection and individual patient outcomes.

Evaluating preferences for profiles of GLP-1 receptor agonists among injection-naïve type 2 diabetes patients in the UK

Objective To use a discrete choice experiment (DCE) to evaluate preferences for the actual treatment features and overall profiles of two injectable glucagon-like peptide-1 receptor agonists (dulaglutide and liraglutide) among patients with type 2 diabetes mellitus (T2DM) in the UK. Methods In-person interviews were conducted in the UK to administer a DCE to patients with self-reported T2DM, naïve to treatment with injectable medications. The DCE examined six attributes of T2DM treatment each described by two levels: “dosing frequency,” “hemoglobin A1c change,” “weight change,” “type of delivery system,” “frequency of nausea,” and “frequency of hypoglycemia.” Part-worth utilities were estimated using random effects logit models and were used to calculate relative importance (RI) values for each attribute. A chi-square test was used to determine differences in preferences for dulaglutide versus liraglutide profiles. Results A total of 243 participants [mean age: 60.5 (standard deviation 10.9) years; 76.1% male; mean body mass index: 29.8 (standard deviation 5.4) kg/m2] completed the study. RI values for the attributes in rank order were: “dosing frequency” (41.6%), “type of delivery system” (35.5%), “frequency of nausea” (10.4%), “weight change” (5.9%), “hemoglobin A1c change” (3.6%), and “frequency of hypoglycemia” (3.0%). Significantly more participants preferred the dulaglutide profile (83.1%) compared with the liraglutide profile (16.9%; P<0.0001). Conclusion This study elicited patients’ preferences for attributes and levels representing the actual characteristics of two specific glucagon-like peptide-1 medications. In this context, dosing frequency and type of delivery system were most important, accounting for over 75% of the RI. While previous studies have identified efficacy as highly important in T2DM medication decisions, this study suggests that when differences in efficacy between medications are small, other treatment features (eg, dosing frequency and delivery system) are of much greater importance to patients.

Review of treatment response in rheumatoid arthritis: assessment of heterogeneity.

Abstract Objective: Rheumatoid arthritis (RA) is a chronic, systemic, progressive, inflammatory disorder. The primary goals of treatment in RA are to reduce the signs and symptoms of disease, prevent progression of joint damage and improve patients’ physical function. Patients with different sociodemographic characteristics, varying degrees of severity of illness, and comorbidities tend to exhibit differential response to treatment. The purpose of this review was to identify a broad set of factors that are associated with and/or predictive of RA treatment response and determine those that warrant further research. Research design and methods: A comprehensive review of the literature from the last 10 years was performed using three key databases (PubMed, EMBASE, and Cochrane). All relevant articles that met the inclusion/exclusion criteria were selected and scored for their levels of evidence using the National Institute of Clinical Excellence (NICE) scoring method. Data on study design, interventions and treatment outcomes were abstracted using a structured abstraction table. Results: A total of 30 articles were included in the review and data abstraction. Besides gender, baseline clinical variables such as C-reactive protein level, erythrocyte sedimentation rate, measures of disease activity, and Health Assessment Questionnaire scores (based on five patient-centered dimensions) were consistently associated with treatment response over time. Conclusions: This comprehensive literature review identified several factors associated with treatment response which might be valuable to include as relevant measures in future studies of RA treatment. Inclusion of these factors, particularly those in the clinical and sociodemographic domains, in the design of future trials will further the understanding that ultimately may help clinicians deliver targeted treatment to community practice RA patients, thus resulting in improved patient outcomes.

A comprehensive review of predictive and prognostic composite factors implicated in the heterogeneity of treatment response and outcome across disease areas

Aim:  To assess and present the current body of evidence regarding composite measures associated with differential treatment response or outcome as a result of patient heterogeneity and to evaluate their consistency across disease areas.

Utility values in diabetic kidney disease: a literature review

Abstract Objective: To summarize the published literature on utilities for health states associated with diabetic kidney disease (DKD), including end-stage renal disease (ESRD). Research design and methods: A literature review was conducted (MEDLINE, MEDLINE in process, EMBASE, NHS EED, HEED, CEA Registry, EconLit, RePEc, and HTA) to identify relevant articles published between January 2000 and July 2013. Results were assessed for relevance by two reviewers in line with the study protocol. Main outcome measures: For eligible studies, data extracted included patient population, health states, methods used to elicit utility values, and the source of the preference values. Results: Twelve studies satisfied the inclusion criteria. They reported various utility and/or disutility scores for different DKD health states using a range of patient populations, utility approaches, and sources of preference values. The most common study country was the USA. Most of the studies collected data at one time point, but two had a longitudinal design. Three different utility instruments – EuroQoL (EQ-5D), Quality of Well-Being Scale (QWB), and 15-dimensional (15D) – were used to elicit utilities indirectly. The Time Trade-Off (TTO) approach was used in one study; another undertook a meta-analysis of published utility studies. Utilities were identified for different health states including DKD, ESRD–no dialysis, ESRD–dialysis, and transplant. One study reported utilities for patients by type of transplant. There was variation in values for the same health state between studies, and none of the studies reported utilities for the different stages of DKD. In the studies that undertook a comparison, utility values for those with DKD were generally found to be lower than those without DKD. Conclusions: This literature review highlights that at present utility scores (or disutility penalties) exist for relatively few health states in DKD. Further studies are needed to produce accurate and comprehensive utility scores that differentiate between different DKD health states.

Health State Utilities Associated With Attributes of Weekly Injection Devices for Treatment of Type 2 Diabetes.

Background Glucagon-like peptide-1 (GLP-1) receptor agonists are often recommended as part of combination therapy for type 2 diabetes when oral medication does not result in sufficient glycemic control. Several GLP-1 receptor agonists are available as weekly injections. These medications vary in their injection delivery systems, and these differences could impact quality of life and treatment preference. The purpose of this study was to estimate utilities associated with attributes of injection delivery systems for weekly GLP-1 therapies.

Patient perceptions of injection devices used with dulaglutide and liraglutide for treatment of type 2 diabetes

Abstract Objective: Liraglutide and dulaglutide have demonstrated similar glycemic efficacy and safety. However, they differ in treatment administration and injection devices. The purpose of this study was to examine and compare patient perceptions of the injection devices used with liraglutide and dulaglutide. Methods: Patients with type 2 diabetes treated with liraglutide or dulaglutide were recruited from across the US. Patients completed the Diabetes Injection Device Experience Questionnaire (DID-EQ) to rate their current injection device. Patients who had experience with both treatments also completed the Diabetes Injection Device Preference Questionnaire (DID-PQ) to report preferences between the two devices. ANCOVAs were conducted to compare DID-EQ scores between dulaglutide and liraglutide patients, while controlling for covariates. Descriptive statistics are presented for preferences reported on the DID-PQ. Results: A total of 404 patients were recruited from 49 states (mean age = 60.7 years; 54.0% female; 204 liraglutide; 200 dulaglutide). Mean DID-EQ item scores for both treatments were high, ranging from 3.48 to 3.90 on a 4 point scale. ANCOVAs found significantly higher scores for dulaglutide than liraglutide on DID-EQ global items assessing ease of use (3.82 vs. 3.73, p = .040) and convenience (3.79 vs. 3.66, p = .004). Among the 58 patients who had used both devices, more patients reported a preference for the dulaglutide device than the liraglutide device on every item of the DID-PQ. Conclusions: High DID-EQ scores indicate positive perceptions of both the liraglutide and dulaglutide injection devices. The dulaglutide device was associated with slightly higher scores for ease of use and convenience than the liraglutide device.

Development of the Diabetes Injection Device Experience Questionnaire (DID-EQ) and Diabetes Injection Device Preference Questionnaire (DID-PQ)

BackgroundPrevious research has examined patient perceptions of insulin injection devices. However, injectable medications other than insulin are increasingly used to treat type 2 diabetes, including GLP-1 receptor agonists. No patient-reported outcome (PRO) instruments have been developed taking into account the experiences of patients using newer injection devices, which are often different from devices used for insulin. Therefore, the purpose of this qualitative study was to develop two draft PRO instruments focusing on patients’ experiences with these newer injection devices (one instrument assessing perceptions of a single injection device, and another assessing preferences between two devices).MethodsQuestionnaire development proceeded in six steps: literature review, interviews with six device experts, concept elicitation interviews with patients (N = 32), preliminary translatability assessment, cognitive interviews with patients (N = 20), and final translatability assessment.ResultsLiterature review and expert interviews were conducted to inform a concept elicitation interview guide. In concept elicitation in the US, UK, and Germany, patients with type 2 diabetes reported a range of injection features that influenced their perceptions of non-insulin injection devices (e.g., requirements for preparation of the medication/device, issues related to the needle, ease-of-use, portability). Two draft “item pools” were developed based on the literature review, expert interviews, and concept elicitation results. In cognitive interviews, patients recommended minor revisions and indicated that the draft instruments were generally clear, comprehensible, and relevant to their experience with non-insulin injectable medication. The instruments were refined based on the cognitive interviews and translatability assessment, resulting in two questionnaires.ConclusionsThe various steps of qualitative research support the content validity of these new PRO instruments, which are the first developed specifically to assess perceptions of non-insulin injection delivery systems. Despite some overlap with insulin-focused questionnaires, the new instruments are distinct from previous instruments (omitting content that would not be relevant to patients receiving non-insulin injectable treatment, while including content that is not included in the insulin focused instruments). This qualitative research yielded two draft questionnaires that are grounded in patient perceptions and ready for psychometric validation studies with larger samples of patients with type 2 diabetes.