Joshua D. Epstein

Response shift: a brief overview and proposed research priorities

AimThe objective of this overview is to review current methodologies of response shift research in patient-reported outcomes to facilitate and stimulate further research in this area.MethodsThis paper is a narrative overview of research in response shift.ResultsThe following research priorities emerged: (1) obtain a consensus on terminology and theoretical models used, to ensure that all researchers and clinicians are at the same starting point; (2) determine the clinical importance of response shift; (3) determine the best way to measure and adjust for response shift as a clinically important confounder; (4) ascertain how response shift can best be identified when response shift is the focus of clinical treatment; and (5) establish what methods can be used to translate response shift knowledge into real-world settings.ConclusionsWith the adoption of these research priorities, we anticipate that the theories and processes of response shift will be better understood, current methods to analyze this phenomenon will be improved while new ones may also be developed, and the clinical importance and impact of response shift in measuring changes in health-related quality of life (HRQL) will be determined.

Doxepin rinse for management of mucositis pain in patients with cancer: one week follow-up of topical therapy.

This study assessed the effectiveness of oral doxepin rinse for mucositis-related pain management in patients following 1 week of repeated dosing. Patients with oral mucositis due to head and neck radiation therapy or hematopoietic stem cell transplant (HSCT) were recruited to participate in a 1-week follow-up study. Subjects who gave informed consent rinsed with doxepin (5 ml) during the initial visit and were then told to use doxepin rinse over the next week as needed, three to six times per day, and return for a follow-up visit. At each visit, mucositis was scored using the Oral Mucositis Assessment Scale and oral pain was assessed using a visual analogue scale before and after rinsing. The use of a systemic analgesic was recorded, and side effects were documented. At the follow-up visit, subjects were also asked to retrospectively report average pain scores they experienced over the past week, 5 and 15 minutes following rinse. Nine subjects were enrolled in the study. Statistically significant reductions in pain scores were reported for 2 hours following doxepin rinse during the initial visit (p < .05). Patients recalled that their pain significantly dropped within 5 minutes of rinsing over the week of repeated dosing (p < .05). At the follow-up visit, subjects reported statistically significant pain reduction 5 minutes after doxepin rinsing (p < .05). These results indicate that doxepin rinsing continues to produce reduced intensity of pain levels over a 1-week span of repeated dosing.

Oral Doxepin Rinse: The Analgesic Effect and Duration of Pain Reduction in Patients with Oral Mucositis Due to Cancer Therapy

This research expands on our prior study, in which we assessed pain reduction after topical doxepin rinse in patients with oral mucositis resulting from cancer and cancer therapy. We continued to enroll patients with painful oral mucositis attributable solely to cancer therapy and performed further analysis on the duration of pain reduction. Fifty-one patients with oral mucositis were enrolled. Mucositis was scored and oral pain was assessed with a visual analog scale before doxepin oral rinse (5 mg/mL) and at regular intervals up to 4 h after rinsing. Of those who reported pain reduction, 95% did so within 15 min of rinsing with doxepin. In the total sample, the average patient reported a 70% maximum decrease in pain (P < 0.0001). Recurrence of pain was slow and at the conclusion of the study 19 patients (37%) still reported a reduction from baseline pain. With this censored data we used Cox-proportional hazards to determine what variables best explained longer duration of pain reduction. Our final model determined that more severe baseline pain, worse mucosal erythema score, or a larger relative maximum reduction in pain were all associated with a slower rate of pain recurrence after oral rinsing (all P < 0.01).

Cost of care for early- and late-stage oral and pharyngeal cancer in the California Medicaid population†

This study documents the direct medical costs associated with treating oral and pharyngeal squamous cell carcinoma (OSCC) as early‐ or late‐stage disease according to the current standard of care.

A Budget Impact Model of Hemophilia Bypassing Agent Prophylaxis Relative to Recombinant Factor VIIa On-Demand

BACKGROUND Hemophilia patients use factor-clotting concentrates (factor VIII for hemophilia A and factor IX for hemophilia B) for improved blood clotting. These products are used to prevent or stop bleeding episodes. However, some hemophilia patients develop inhibitors (i.e., the patients immune system develops antibodies against these factor concentrates). Hence, these patients do not respond well to the factor concentrates. A majority of hemophilia patients with inhibitors are managed on-demand with the following bypassing agents: recombinant factor VIIa (rFVIIa) and activated prothrombin complex concentrate (aPCC). The recently published U.S. registries Dosing Observational Study in Hemophilia (DOSE) and Hemostasis and Thrombosis Research Society (HTRS) reported higher rFVIIa on-demand use for bleed management than previously described. OBJECTIVE To estimate aPCC and rFVIIa prophylaxis costs relative to rFVIIa on-demand treatment cost based on rFVIIa doses reported in U.S. registries. METHODS A literature-based cost model was developed assuming a base case on-demand annual bleed rate (ABR) of 28.7 per inhibitor patient, which was taken from a randomized phase 3 clinical trial. The doses for rFVIIa on-demand were taken from the median dose per bleed reported by the DOSE and HTRS registries. Model inputs for aPCC and rFVIIa prophylaxis (i.e., dosing and efficacy) were derived from respective randomized clinical trials. Cost analysis was from the U.S. payer perspective, and only direct drug costs were considered. The drug cost was based on the Medicare Part B 2014 average sale price (ASP). Two-way sensitivity and threshold analyses were performed by simultaneously varying on-demand ABR, prophylaxis efficacy, and unit drug cost. In addition to studying relative costs associated with on-demand and prophylaxis treatments, relative cost per bleeding episode avoided were also calculated for aPCC and rFVIIa prophylaxis treatments. The prophylaxis efficacy reported in the trials were used to determine the number of bleeding episodes avoided. RESULTS Based on the median on-demand dose of 695 mcg per kg per bleed, reported by the DOSE registry, the annual rFVIIa on-demand cost was

Analysis of oral lesion biopsies identified and evaluated by visual examination, chemiluminescence and toluidine blue

34,009 per kg of body weight. The annual rFVIIa on-demand cost was

The efficacy of oral lumenoscopy™ (ViziLite®) in visualizing oral mucosal lesions

22,020 per kg of body weight when the median dose of 450 mcg per kg per bleed reported by the HTRS registry was considered. The annual cost rose to

Opinions Regarding the Academy of Managed Care Pharmacy Dossier Submission Guidelines: Results of a Small Survey of Managed Care Organizations and Pharmaceutical Manufacturers

38,461 per kg of body weight when the rFVIIa on-demand dose of 786 mcg per kg per bleed among patients infusing an initial dose ≥ 250 mcg per kg was considered. The aPCC (85 units per kg per every other day) and rFVIIa (90 mcg per kg per every day) annual prophylaxis costs were

Management of pain in cancer patients with oral mucositis: follow-up of multiple doses of doxepin oral rinse.

26,536 and

Separating gains and losses in health when calculating the minimum important difference for mapped utility measures

60,700, respectively. Also, aPCC and rFVIIa prophyaxis treatments were estimated to prevent a total of 20.8 and 12.9 annual bleeding episodes, respectively. When compared with the on-demand dose of 695 mcg per kg per bleed (DOSE registry), the annual aPCC and rFVIIa prophylaxis costs were 21.9% lower and 78.4% higher, respectively. Additionally, aPCC prophylaxis saved