Background : MCL is an aggressive B-cell non-Hodgkin lymphoma with poor prognosis. Pts with R/R MCL typically experience low overall response rates (ORRs) and short remissions. Bruton tyrosine kinase ...(BTK) is a clinically validated target in MCL. Acalabrutinib (ACP-196) is a highly selective, potent, covalent inhibitor of BTK with minimal off-target activity. The Phase 2 ACE-LY-004 study assessed acalabrutinib monotherapy in R/R MCL pts.
Methods: Eligible pts were aged ≥18 y with confirmed MCL, ECOG PS ≤2, and had relapsed after or were refractory to 1-5 prior therapies. Exclusion criteria included prior BTK or BCL-2 inhibitor exposure and concomitant warfarin or equivalent vitamin K antagonists. Acalabrutinib was administered orally at 100 mg twice daily until progressive disease (PD) or unacceptable toxicity. The primary endpoint was ORR (complete response CR + partial response) by investigator assessment based on the Lugano Classification (Cheson, et al. 2014). Secondary endpoints included ORR by Independent Review Committee (IRC) assessment, duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, pharmacokinetics (PK) and pharmacodynamics. Time to response (TTR) was an exploratory endpoint.
Results: 124 pts from 9 countries were treated. Median age was 68 y (range 42-90) with 65% aged ≥65 y. Baseline characteristics included ECOG PS ≤1 (93%), bulky lymph nodes ≥10 cm (8%), extranodal involvement (73%) and intermediate/high risk simplified MCL International Prognostic Index scores (44%/17%). Median number of prior therapies was 2 (range 1-5); 24% were refractory to the most recent prior treatment. Acalabrutinib PK parameters indicated rapid absorption and elimination. Median BTK target occupancy at steady state was 99% 4 h after dosing and 95% at trough (12 h after dosing). As of Feb 28, 2017, median time on study was 15.2 mo (range 0.3-23.7). Investigator-assessed ORR was 81% (95% CI, 73%-87%), with 40% (95% CI, 31%-49%) achieving CR (Table). High concordance (91% and 94%) was observed between investigator- and IRC-assessed ORR and CR, respectively. ORR and CR rates were consistent across prespecified subgroups of age, tumor bulk (≥10 cm) and number/type of prior treatment. Median TTR was 1.9 mo (range 1.5-4.4). Median DOR was not reached (NR); the 12-mo DOR was 72% (95% CI, 62%-80%). DOR by best response is shown in the figure. Median PFS and OS were NR. The 12-mo PFS and OS rates were 67% (95% CI, 58%-75%) and 87% (95% CI, 79%-92%), respectively. The most frequent adverse events (AEs; ≥20%) were primarily Grade 1/2 and included headache (38%), diarrhea (31%), fatigue (27%) and myalgia (21%). Grade 3/4 AEs (≥5%) included neutropenia (10%), anemia (9%) and pneumonia (5%). There were no cases of atrial fibrillation and 1 case of Grade 3 hypertension (1%), The most common bleeding events were contusion (13%) and petechiae (9%); all bleeding events were Grade 1/2 except one event of Grade 3 gastrointestinal (GI) hemorrhage occurring in 1 pt (1%) with a history of a GI ulcer. Tumor lysis syndrome (Grade ≥3) was reported in 3 pts (2%) and all cases occurred after treatment discontinuation due to disease progression. Second primary malignancies occurred in 8 pts (6%), 4 of which were skin neoplasms. One Grade 5 AE was reported in a pt with a history of aortic stenosis who died of worsening aortic stenosis not considered related to study treatment. Median relative dose intensity (ratio of actual to planned cumulative dose during drug exposure period) was 99% (range 27%-100%). Treatment discontinuation was primarily due to PD (31%) and AE (6%). AEs leading to discontinuation occurred in only one pt each and were aortic stenosis, B-cell lymphoma (DLBCL), blood blister and petechiae (both in 1 pt with Grade 3 acute coronary syndrome which was treated with Plavix, resulting in blood blister/petechiae formation considered related), dyspnea and leukostasis syndrome (in the same pt), noncardiac chest pain, pulmonary fibrosis and thrombocytopenia. At cutoff, 56% of pts remain on treatment.
Conclusions: In R/R MCL pts, treatment with single-agent acalabrutinib resulted in high ORR and CR rates, with durable and clinically meaningful responses. A favorable safety profile was also demonstrated, with a low frequency and severity of AEs and few discontinuations due to AEs. Given this favorable benefit-risk profile, acalabrutinib represents a promising treatment option for R/R MCL.
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Wang:Celgene: Honoraria, Research Funding; Karus: Research Funding; Juno Therapeutic: Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Oncoceutics: Research Funding; BeiGene: Research Funding; Oncternal: Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Kite Pharma: Research Funding; Asana: Research Funding; Acerta Pharma: Consultancy, Honoraria, Research Funding; Novartis: Research Funding; Karyopharm: Research Funding. Rule:TG Therapeutics: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Napp: Consultancy; Kite: Consultancy; Astra-Zeneca: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding. Zinzani:Gilead Sciences: Consultancy; Astellas: Consultancy; Bristol-Myers Squibb: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Lundbeck: Consultancy; Merck: Consultancy; Mundipharma: Consultancy; Nordic Nanovector: Consultancy; Roche: Consultancy; Sandoz: Consultancy; Verastem: Consultancy; Takeda: Consultancy; Servier: Consultancy. Goy:Pharmacyclics / J&J: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding. Casasnovas:Roche: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; BMS: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Smith:Acerta Pharma: Research Funding; Seattle Genetics: Research Funding; Genentech: Research Funding; Merck Sharp and Dohme Corp: Research Funding; Janssen R&D LLC: Research Funding; Pharmacyclics: Research Funding; Portola Pharmaceuticals: Research Funding. Lamy:Roche: Consultancy, Honoraria. Morschhauser:Celgene: Consultancy, Honoraria; Servier: Consultancy; Janssen: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Gilead: Consultancy. Shah:Amgen: Other: Unscripted Interview used for marketing purposes, Speakers Bureau; Incyte: Research Funding; Pfizer: Consultancy; Jazz: Consultancy; Baxalta: Consultancy; Celgene: Consultancy, Other: Unscripted interview used for marketing purposes. Davies:Gilead: Consultancy, Honoraria, Other: Travel expenses to attend conference, Research Funding; Takeda: Consultancy, Honoraria, Other: Travel expenses to attend conference, Research Funding; Bayer: Research Funding; Acerta Phamra: Research Funding; Karyopharma: Honoraria, Research Funding; Celgene: Honoraria, Other: Advisory Board, travel expenses to attend conference, Research Funding; GSK: Research Funding; Janssen: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; CTI: Consultancy, Honoraria, Other: Travel expenses to attend conference; Seattle Genetics: Research Funding. Eek:Ramsey Private Hospital Albury Wodonga: Membership on an entity's Board of Directors or advisory committees; Border Medical Oncology: Employment. Dupuis:Roche: Consultancy. Jacobsen:Merck: Consultancy; Seattle Genetics: Consultancy; Spectrum: Consultancy; Pharmacyclics: Consultancy. Kater:Dept Hematology, Academic Medical Center, Amsterdam, the Netherlands: Employment; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche/Genentech: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Research Funding; Acerta Pharma: Research Funding; Pfizer: Research Funding; Morphosys: Research Funding; Sandoz Novartis: Research Funding; Celtrion: Research Funding; Gilead: Research Funding; TG Therapeutics: Research Funding; Merck: Research Funding. Covey:Acerta: Employment, Equity Ownership; Astra-Zeneca: Equity Ownership. Dua:Acerta Pharma: Employment. Hamdy:Acerta Pharma: Employment, Equity Ownership, Patents & Royalties: Acalabrutinib related patents. Huang:Acerta Pharma: Employment. Izumi:Acerta Pharma: Employment, Equity Ownership. Patel:Acerta Pharma: Employment. Slatter:Astra Zeneca: Equity Ownership; Acerta Pharma: Employment. Jurczak:Nordic Nanovector: Membership on an entity's Board of Directors or advisory committees, Research Funding; Servier: Membership on an entity's Board of Directors or advisory committees, Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Research Funding; Merck: Research Funding; Sandoz Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Research Funding; Celtrion: Research Funding; Jagiellonian University: Employment; Spectrum: Membership on an entity's Board of Directors or advisory committees, Research Fun
Objective
This paper reflects on the recent growth of cancer research being conducted through some of Australia's rural centres. It encompasses work being done across the fields of clinical, ...translational and health services research.
Design
This is a collaborative piece with contributions from rural health researchers, clinical and cancer services staff from several different regions.
Conclusion
The past decade has seen an expansion in cancer research in rural and regional Australia driven in part by the recognition that cancer patients in remote areas experience poorer outcomes than their metropolitan counterparts. This work has led to the development of more effective cancer networks and new models of care designed to meet the particular needs of the rural cancer patient. It is hoped that the growth of cancer research in regional centres will, in time, reduce the disparity between rural and urban communities and improve outcomes for cancer patients across both populations.
Abstract The objective of this study was to examine the agreement between health care professionals’ (HCPs) and patients’ evaluation of health-related quality of life (HRQOL) issues for cancer ...patients with bone metastases. A total of 413 patients and 152 HCPs were interviewed across five centres worldwide. Mean scores were almost always higher for HCPs than for patients. Patients and HCPs agreed that four issues affect HRQOL of bone metastases patients profoundly: ‘long-term (chronic) pain’, ‘difficulty in carrying out usual daily tasks’, ‘able to perform self-care’ and ‘able to perform role functioning’. A substantial difference was found with respect to the perceived importance of psychosocial and somatic issues. Patients emphasised psychosocial issues with a particular focus on ‘worry’ about loss of mobility, dependence on others and disease progression, HCPs however rated ‘symptom’ issues as more important, specifically those related to ‘pain’. In conclusion, patients and HCPs agreed that pain and physical/role functioning are important to the HRQOL of cancer patients with bone metastases, but patients also emphasized the importance of psychosocial issues to HRQOL. This information has been an important component in the development of a health-related quality of life questionnaire for patients with bone metastases (EORTC QLQ-BM 22).
Background: In the pivotal FIRST trial, a randomized, international, multicenter phase 3 study, continuous Rd compared with melphalan-prednisone-thalidomide (MPT) improved progression-free survival ...(PFS) which was the primary endpoint (HR = 0.72; P < 0.01). The interim overall survival (OS) analysis showed a 22% reduction in risk of death with continuous Rd vs. MPT (HR = 0.78; P = 0.02) (Facon, Blood 2013). This analysis evaluates outcomes based on age, which was a stratification parameter, and compared pts aged ≤ 75 yrs and > 75 yrs.
Methods: Pts with NDMM were randomized to continuous Rd until progressive disease (PD) (N = 535); 18 cycles (72 weeks wks) of Rd (Rd18; N = 541); or 12 cycles (72 wks) of MPT (N = 547). Starting doses were reduced in pts aged > 75 yrs: dexamethasone (20 vs. 40 mg), melphalan (0.20 vs. 0.25 mg/kg), and thalidomide (100 vs 200 mg). The primary endpoint was PFS (continuous Rd vs. MPT) and the secondary endpoint were OS, overall response rate, time to response, duration of response, time to Tx failure, time to 2nd AMT, health-related quality of life, safety.
Results: The proportion of pts aged > 75 yrs was > 34% across treatment (Tx) arms. In pts ≤ 75 yrs, 37% had ISS stage III vs. 51% in > 75 yrs. ECOG score ≥ 1 was observed in 74% and 69% of pts aged > 75 and ≤ 75 yrs, respectively. Severe renal impairment (CrCl < 30 mL/min) was observed in 14% of pts > 75 vs. 7% in ≤ 75 yrs. PFS and OS outcomes favored continuous Rd over MPT in both age groups. With a median follow-up of 37 months (mos), PFS was 27.4 mos in continuous Rd pts vs. 21.8 mos in MPT pts aged ≤ 75 yrs (HR = 0.68; P < 0.001); a trend for improved PFS was also seen for pts aged > 75 yrs (HR = 0.81; P = 0.11) (Table 1). PFS for continuous Rd vs. Rd18 pts was also increased in both age groups (HR = 0.68; P < 0.001 and HR = 0.75; P = 0.03, respectively). Response rates were consistently higher with continuous Rd vs. MPT in pts aged ≤ 75 yrs (77% vs. 66%; P < 0.001) and > 75 yrs (71% vs. 55%; P < 0.001). Duration of response with continuous Rd was longer vs. MPT in pts aged ≤ 75 yrs (40 vs. 22 mos) and pts > 75 yrs (31 vs. 24 mos). The interim analysis of OS showed an improved trend for continuous Rd vs. MPT in pts aged ≤ 75 yrs (HR = 0.77; P = 0.06) and > 75 yrs (HR = 0.80; P= 0.16). Grade 3–4 adverse events (AEs) in ≥ 10% of pts were similar across age subgroups (Table 2). Tx discontinuation due to AEs was comparable across the Tx groups and independent of age.
Conclusions:Regardless of age (≤ 75 vs. > 75 yrs), continuous Rd was effective, increased PFS and interim OS, and was generally well tolerated vs. MPT in NDMM pts. Duration of response was improved with continuous Rd vs. MPT and Rd18, irrespective of age, and with a more profound benefit observed in younger pts. Continuous Rd represents a new clinical option and standard of care for these pts in the first-line setting.
Abstract 81. Table 1PFS, OS and ResponseAged ≤ 75 yrsAged > 75 yrsAll ptsITT populationContinuous Rd (n = 349)Rd18 (n = 348)MPT (n = 359)Continuous Rd (n = 186)Rd18 (n = 193)MPT (n = 188)Continuous Rd (n = 535)Rd18 (n = 541)MPT (n = 547)Median PFS, mos27.421.321.821.219.419.225.520.721.2PFS HR (95% CI); P-valueContinuous Rd vs. Rd180.68 (0.55–0.83); P < 0.010.75 (0.58–0.98); P = 0.030.70 (0.60–0.82); P < 0.01Continuous Rd vs. MPT0.68 (0.56–0.83); P < 0.010.81 (0.62–1.05); P = 0.110.72 (0.61–0.85); P < 0.014-yr OS, %666158474739595651OS HR (95% CI); P-valueContinuous Rd vs. Rd180.88 (0.67–1.16); P = 0.360.94 (0.69–1.29); P = 0.700.90 (0.73–1.10); P = 0.31Continuous Rd vs. MPT0.77 (0.59–1.01); P = 0.060.80 (0.59–1.09); P = 0.160.78 (0.64–0.96); P = 0.02Response rate (≥ PR), %777766716655757362Duration of response (≥ PR), mos402322312024352222CI, confidence interval; ITT, intent to treat; PR, partial response.
Table 2Grade 3–4 AEs Observed in ≥ 10% of PtsAged ≤ 75 yrsAged > 75 yrsSafety population, %Continuous Rd (n = 347)Rd18 (n = 348)MPT (n = 357)Continuous Rd (n = 185)Rd18 (n = 192)MPT (n = 184)Neutropenia282547282940Thrombocytopenia8913977Anemia181220192317Leukopenia5611458Infections292116292320DVT and/or PE1068784Peripheral sensory neuropathy1110108Tx discontinuation due to AEs281828322530DVT, deep-vein thrombosis; PE, pulmonary embolism.
Hulin:Celgene: Honoraria. Off Label Use: Lenalidomide used in newly diagnosed multiple myeloma patients. Facon:Celgene: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Belch:Janssen, Celgene, Onyx: Honoraria. Petrucci:Celgene, Janssen-Cilag, Sanofi, Bristol-Myers Squibb: Honoraria. Dührsen:Celgene: Honoraria, Research Funding. Song:Celgene: Consultancy, Honoraria, Research Funding. Houck:Celgene: Employment. Chen:Celgene: Employment. Ervin-Haynes:Celgene: Employment.
Locoregional recurrence is a harbinger of disseminated disease, and historically the estimated 5-year survival when treated with local therapy only varies between 21% and 37%. The role of systemic ...treatment after local treatment is unclear at present. The authors investigated the results of systemic chemotherapy for these patients after complete local surgical resection. Data on 80 patients were evaluable for toxicity, time to treatment failure (TTF), and survival. Sixty-four patients received doxorubicin-based treatments, four received methotrexate-based combinations, and 12 received tamoxifen only. Among the 68 patients treated with cytostatics, there were two possible treatment-related deaths. Two patients developed grade 3 neutropenia, four developed grade 3 vomiting, and 42 had grade 2 toxicity. The 2- and 5-year disease free survival at a mean follow-up period of 5.5 years were 56% and 38%, respectively. The projected median TTF was 32 months (95% confidence interval, 23-82). Two- and 5-year overall survival were 86% and 62%, respectively, with a projected median survival of 93 months (7.75 years; 95% confidence interval, 64-177). These results show systemic therapy improved TTF and survival for patients with stage IV, no-evidence-of-disease breast cancer. Randomized studies are needed to confirm these findings and define optimal therapy.
Abstract
Aims
The non-invasive myocardial work index (MWI) has been validated in patients without aortic stenosis (AS). A thorough assessment of methodological limitations is warranted before this ...index can be applied to patients with AS.
Methods and results
We simultaneously measured left ventricular pressure (LVP) by using a micromanometer-tipped catheter and obtained echocardiograms in 20 patients with severe AS. We estimated LVP curves and calculated pressure–strain loops using three different models: (i) the model validated in patients without AS; (ii) the same model, but with pressure at the aortic valve opening (AVO) adjusted to diastolic cuff pressure; and (iii) a new model based on the invasive measurements from patients with AS. Valvular events were determined by echocardiography. Peak LVP was estimated as the sum of the mean aortic transvalvular gradient and systolic cuff pressure. In same-beat comparisons between invasive and estimated LVP curves, Model 1 significantly overestimated early systolic pressure by 61 ± 5 mmHg at AVO compared with Models 2 and 3. However, the average correlation coefficients between estimated and invasive LVP traces were excellent for all models, and the overestimation had limited influence on MWI, with excellent correlation (r = 0.98, P < 0.001) and good agreement between the MWI calculated with estimated (all models) and invasive LVP.
Conclusion
This study confirms the validity of the non-invasive MWI in patients with AS. The accuracy of estimated LVP curves improved when matching AVO to the diastolic pressure in the original model, mirroring that of the AS-specific model. This may sequentially enhance the accuracy of regional MWI assessment.
Graphical Abstract
Graphical Abstract
Synopsis of the study design, key findings, and conclusions. Estimations and calculations based on Model 1 (red-dashed line) and Model 2 (blue-dashed line), where the pressure at AVO is adjusted to the diastolic cuff pressure and invasively measured LVP (grey line). AVC, aortic valve closure; AVO, aortic valve opening; MVC, mitral valve closure; MVO, mitral valve opening; LVP, left ventricular pressure; STE, speckle-tracking echocardiography.
In the phase 3 SOLO2 trial (ENGOT Ov-21), maintenance therapy with olaparib tablets significantly prolonged progression-free survival (primary endpoint) compared with placebo in patients with a ...germline BRCA1 or BRCA2 (BRCA1/2) mutation and platinum-sensitive, relapsed ovarian cancer who had received two or more lines of previous chemotherapy. The most common subjective adverse effects included fatigue, nausea, and vomiting, which were typically low grade and self-limiting. Our a-priori hypothesis was that maintenance olaparib would not negatively affect health-related quality of life (HRQOL) and additionally that the prolongation of progression-free survival with olaparib would be underpinned by additional patient-centred benefits.
In SOLO2, 196 patients were randomly assigned to olaparib tablets (300 mg twice daily) and 99 to placebo. Randomisation was stratified by response to previous chemotherapy (complete vs partial) and length of platinum-free interval (>6–12 vs >12 months). The prespecified primary HRQOL analysis evaluated the change from baseline in the Trial Outcome Index (TOI) score during the first 12 months of the study. To be assessable, patients had to have an evaluable score at baseline and at least one evaluable follow-up form. Secondary planned quality-of-life (QOL) analyses included the duration of good quality of life (defined as time without significant symptoms of toxicity TWiST and quality-adjusted progression-free survival QAPFS). Efficacy and QOL outcomes were analysed in all randomly assigned patients (the full analysis set), and safety outcomes were analysed in all randomly assigned patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01874353, and is closed to new participants.
The adjusted average mean change from baseline over the first 12 months in TOI was −2·90 (95% CI −4·13 to −1·67) with olaparib and −2·87 (–4·64 to −1·10) with placebo (estimated difference −0·03; 95% CI −2·19 to 2·13; p=0·98). Mean QAPFS (13·96 SD 10·96 vs 7·28 5·22 months; difference 6·68, 95% CI 4·98–8·54) and mean duration of TWiST (15·03 SD 12·79 vs 7·70 6·42 months; difference 7·33, 95% CI 4·70–8·96) were significantly longer with olaparib than with placebo.
Olaparib maintenance therapy did not have a significant detrimental effect on HRQOL compared with placebo. There were clinically meaningful patient-centred benefits in both TWiST and QAPFS despite the adverse effects associated with olaparib. These patient-centred endpoints support the improvement in progression-free survival, the primary endpoint in SOLO2, and should be included in future trials of maintenance therapies.
AstraZeneca.
The aim of this study was to develop a toolset that can be used by site managers to assess and monitor natural attenuation processes in sediments contaminated with legacy hydrophobic organic ...contaminants. The toolset is composed of sediment traps to measure quality and deposition rate of incoming sediment under different hydrodynamic conditions, sediment cores to show trends in sediment bed concentrations over time, and passive samplers attached to a porewater probe frame to assess the mobility of buried contaminants and possible contaminant flux from sediment. These three tools were used together for the first time to assess the mobility of dichlorodiphenyltrichloroethane (DDT) contaminants in sediment in Pallanza Bay, Lake Maggiore, Italy. Depositing sediment and sediment cores were consistent in showing that DDT-contaminated sediment is undergoing burial by cleaner sediment. Elevated DDT concentrations from historical contamination seemed to be effectively buried and immobilized by ongoing deposition by cleaner sediment, because the positive flux from the elevated DDT concentration in the sediment porewater should not advance towards the sediment surface. The monitoring toolset introduced in this study enabled us to more effectively assess ongoing natural attenuation processes and provide more risk relevant data than traditional methods used in monitored natural recovery projects, such as bulk sediment concentrations from sediment cores. Our field assessment results suggest that incoming sediment from the Toce River have reduced DDT concentrations in the sediment compared to historic levels, and will continue to do so in locations where higher DDT concentrations are found within the bioactive layer.
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•Toolset demonstrates natural attenuation processes for contaminated sediments.•Natural recovery occurring faster in areas with higher deposition rates.•Buried DDT contaminants are effectively immobilized by clean sediment deposition.
Introduction
There is a need to understand how patients assess perceived benefits and risks of treatments.
Objectives
The study aimed to (i) elucidate how patients evaluate treatment experiences and ...(ii) develop a brief patient-reported outcome (PRO) instrument for use across disease areas for perceived benefit–risk evaluation of a new medicine in a clinical trial setting.
Methods
Concepts relating to patient-perceived benefit–risk were identified from literature reviews and qualitative concept elicitation interviews with patients across a variety of primary medical conditions. Draft instrument items were developed from identified concepts and evaluated for clarity, relevance and appropriateness of response options in cognitive interviews. Items were iteratively revised to address patient feedback.
Results
Qualitative interviews were conducted with 47 patients (primary condition: 20 oncological, 12 respiratory, 10 metabolic, 5 cardiovascular), of whom 32 contributed to concept elicitation and 42 to cognitive debriefing. Elicited concepts could be grouped into four medication-related categories: effectiveness of treatment, burden of side effects, convenience of use and overall acceptance/satisfaction. Cost, trial experience and altruism were additional concept categories unrelated to medication. The final instrument contained one item each on the medication’s effectiveness, side effects and convenience, and an overall item capturing patient benefit–risk assessment. An upfront question was included to separate out non-medication aspects of patients’ experiences.
Conclusion
We developed a brief PRO instrument, the Patient Global Impression of Benefit–Risk (PGI-BR), which can be applied across disease areas to assess patient views of benefit–risk of a new medicine in the clinical trial setting.
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