Ravinder Dhawan

The Health-Related Quality of Life and Economic Burden of Constipation

Constipation is a prevalent condition that disproportionately affects women and older adults and leads to self-medication and/or medical consultation. It occurs as a result of functional idiopathic causes or secondarily as a result of a variety of factors including dietary and exercise patterns, adverse effects of medication and disease processes. Constipation is often perceived to be a benign, easily treated condition with short-term treatment being relatively straightforward; however, chronic constipation is associated with mild complications that, left untreated, can develop into more serious bowel complaints (faecal impaction, incontinence and bowel perforations) with further implications for healthcare costs and the patient’s health-related quality of life (HR-QOL). This review summarises the evidence of the HR-QOL impact and economic burden of constipation on patients.Relatively few studies have systematically explored the HR-QOL and economic impact of constipation; however, the existing evidence suggests that HR-QOL is lower in patients with constipation than in non-constipated individuals, and treatments for constipation improve HR-QOL. Additionally, constipation represents an economic burden for the patient and healthcare provider. Resource utilisation associated with the diagnosis and management of constipation is a significant cost driver, whereas constipation prevention programmes have demonstrated cost savings.

Descriptive and Prognostic Value of Patient-Reported Outcomes: The Bortezomib Experience in Relapsed and Refractory Multiple Myeloma

PURPOSE Bortezomib, a boronic acid dipeptide, has been recently introduced as a new approach to treating multiple myeloma (MM). The goal of this work was to evaluate the added value of patient-reported outcomes (PRO) in the interpretation of bortezomib clinical trial outcomes. PATIENTS AND METHODS Two hundred two patients with relapsed, refractory MM were treated with bortezomib as part of the SUMMIT (Study of Uncontrolled Multiple Myeloma Managed with Proteasome Inhibition Therapy) study. Patients were administered the following four PRO measures at several time points: the European Organisation for Research and Treatment of Cancer (EORTC) core Quality of Life Questionnaire (QLQ-C30) and the myeloma-specific module (QLQ-MY24), the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue scale, and the Functional Assessment of Cancer Therapy (FACT)/Gynecologic Oncology Group (GOG) Neurotoxicity (Ntx) scale. Minimal important difference (MID) thresholds were used to define patients as improved, stable, or worsened. A survival analysis was conducted to assess the predictive power of PRO data. RESULTS For the total population, there was a positive change between baseline and best end point. Consistent with the clinical responses, change in PRO scores showed statistically significant differences between response groups with PRO improvement in patients with complete response (CR) or partial response (PR), mostly stable scores in patients with minor response or no change, and deterioration in most scores for patients with progressive disease. Change in scores for neuropathy-related symptoms was reasonably stable. In contrast, fatigue scores significantly improved for patients with CR or PR. When various MID thresholds were applied, the proportion of improved patients exceeded 35% for several domains within all change group definitions. Moreover, survival analysis results demonstrated the additional prognostic information PRO data can provide to supplement clinical data. CONCLUSION This study demonstrated the complementary value for PRO assessments in further interpreting clinical response, the impact of adverse effects, and patient prognosis in clinical trials.

The Cost-Effectiveness of Initial Treatment of Multiple Myeloma in the U.S. With Bortezomib Plus Melphalan and Prednisone Versus Thalidomide Plus Melphalan and Prednisone or Lenalidomide Plus Melphalan and Prednisone With Continuous Lenalidomide Maintenance Treatment

The outlook for transplant-ineligible multiple myeloma patients has improved enormously over recent years with the incorporation of new agents into standard regimens. Novel regimens combine melphalan and prednisone (MP) with bortezomib (VMP), with thalidomide (MPT), and with lenalidomide with (MPR-R) and without (MPR) lenalidomide maintenance. The efficacy, safety, and cost-effectiveness of these regimens have not yet been compared; therefore, we conducted a pharmacoeconomic analysis using data from randomized controlled trials versus MP. Using a Markov model developed from a U.S. payers perspective, we compared VMP with MPT and MPR-R over a lifetime horizon. MPT and MPR-R were chosen because, like VMP, they are superior to MP in response and outcomes. Data from the Velcade as Initial Standard Therapy in Multiple Myeloma (VISTA; VMP), Intergroupe Francophone du Myelome (IFM) 99-06 (MPT), and MM-015 (MPR-R) trials were used. The IFM 99-06 study was selected because of the superior activity in this study compared with other MPT studies. Using patient-level (VMP) and published (MPT, MPR-R) data, we estimated the health-state transition and adverse event probabilities for each regimen, related costs, and state-specific utility estimates. Costs (in 2010 U.S. dollars) and health outcomes were discounted at 3%. Discounted lifetime direct medical costs were lowest with VMP at

The cost‐effectiveness of bortezomib in relapsed/refractory multiple myeloma: Swedish perspective

119,102. MPT cost

Real-world Characteristics and Outcomes of Patients With Metastatic Castration-resistant Prostate Cancer Receiving Chemotherapy Versus Androgen Receptor-targeted Therapy After Failure of First-line Androgen Receptor-targeted Therapy in the Community Setting

142,452 whereas MPR-R cost

Patient-reported outcomes helped predict survival in multiple myeloma using partial least squares analysis.

248,358. Incremental cost-effectiveness ratio calculations projected that VMP would confer cost savings and better health outcomes relative to MPT and MPR-R. We conclude that VMP is highly likely to be cost-effective compared with MP, MPT, and MPR-R.

Economic Evaluation of Bortezomib (VELCADE) for Relapsed and Refractory Multiple Myeloma.

Objectives:  To estimate the cost‐effectiveness of bortezomib (BTZ) compared with dexamethasone (DEX) and lenalidomide plus dexamethasone (LEN/DEX) for the treatment of relapsed/refractory multiple myeloma in Sweden.

The Cost-Effectiveness of Bortezomib Plus Melphalan and Prednisone Versus Lenalidomide Plus Melphalan and Prednisone with Continuous Lenalidomide Maintenance Treatment for the Initial Treatment of Multiple Myeloma In the United States

Background In metastatic castration‐resistant prostate cancer (mCRPC), optimal treatment sequences are unknown. We assessed second‐line taxane (TT) versus androgen receptor‐targeted therapy (ART), after initial ART failure, in United States oncology community practices. Patients and Methods Using electronic medical records, patients with mCRPC receiving first‐line ART and second‐line therapy (TT, ART) were identified. Response and overall survival (OS) were evaluated from second‐line therapy initiation. Multivariate analyses were adjusted for year, age, metastases, opioid use, prostate‐specific antigen (PSA), hemoglobin, alkaline phosphatase, and albumin levels. Results Of 546 patients receiving first‐line ART, 206 and 340 received second‐line TT and ART. Compared with patients receiving second‐line ART, patients receiving TT were younger (median, 74 vs. 79 years), more had intermediate‐high Halabi risk scores (59% vs. 35%), had higher opioid use (42% vs. 22%), median PSA (116 vs. 48 ng/mL), alkaline phosphatase (112 vs. 87 U/L), and lactate dehydrogenase (254 vs. 201 U/L), and had lower hemoglobin (11.2 vs. 12.3 g/dL) and albumin levels (3.8 vs. 4.0 g/dL); all P < .001. Response rates were higher with second‐line TT versus ART (clinical response, 44.2% vs. 24.7%; P = .006; PSA response, 44.5% vs. 28.7%; P = .004). OS did not differ between cohorts (hazard ratio [HR], 0.90; P = .511). Among patients with a poor prognosis (hemoglobin < 11 g/d; albumin < lower limit of normal), those receiving second‐line TT versus ART showed improved OS (HR, 0.52; P = .004 and HR, 0.36; P = .003, respectively). Conclusions Despite more severe disease profiles, patients with mCRPC receiving second‐line TT versus ART achieved higher response rates after initial ART. Poor prognosis patients had improved OS with second‐line TT versus ART. Microabstract Optimal treatment sequences for metastatic castration‐resistant prostate cancer are unknown. This retrospective study assessed outcomes in patients with metastatic castration‐resistant prostate cancer receiving second‐line taxane chemotherapy versus second‐line androgen receptor‐targeted therapy (ART), after failure of first‐line ART, in a real‐world setting. In patients who have previously recieved ART, second‐line taxane chemotherapy, versus alternative ART, may be associated with improved outcomes, particularly among patients with a worse disease prognosis.