Treatment Sequencing in Advanced BRAF-Mutant Melanoma Patients: Current Practice in the United States.

Background: Treatment of advanced BRAF-mutant melanoma has changed dramatically in the past 3 years thanks to the approval of new immunotherapy and targeted therapy agents. Objectives: The goal of our survey was to investigate when immunotherapy and targeted therapy are used in the management of advanced melanoma patients and whether differences exist between the types of setting. Methods: Oncologists from academic centers, community-based centers, and private clinics were invited to participate in an online survey. Survey questions addressed the proportion of BRAF-mutant patients per treatment line, proportion of patients on targeted therapy and immunotherapy available in the United States, and reasons for prescribing each drug class. Results: A total of 101 physicians completed the survey, of which 47 worked in a private clinic, 33 in an academic center, and 21 in a community-based center. Academic center participants tended to see more severe patients (P < .001) and had more patients in second-line treatment than participants from other setting types. In addition, academic center physicians had more patients in clinical trials (P < .001), and they prescribed the ipilimumab and nivolumab combination more frequently. In terms of sequencing, all participants used targeted therapy for severe or rapidly progressing patients and immunotherapy for those who were less severe or slowly progressing. Conclusions: The findings illustrate the differences in treatment approach per type of setting, with patients in academic centers more likely to receive recently approved products or to be enrolled in clinical trials than those in community-based settings.

Building a drug development database: challenges in reliable data availability.

CONTEXT: Policy and legislative efforts to improve the biomedical innovation process must rely on a detailed and thorough analysis of drug development and industry output. OBJECTIVE: As part of our efforts to build a publicly-available database on the characteristics of drug development, we present work undertaken to test methods for compiling data from public sources. These initial steps are designed to explore challenges in data extraction, completeness and reliability. Specifically, filing dates for Investigational New Drugs (IND) applications with the U.S. Food and Drug Administration (FDA) were chosen as the initial objective data element to be collected. MATERIALS AND METHODS: FDA's Drugs@FDA database and the Federal Register (FR) were used to collect IND dates for the 587 New Molecular Entities (NMEs) approved between 1994 and 2014. When available, the following data were captured: approval date, IND number, IND date and source of information. RESULTS: At least one IND date was available for 445 (75.8%) of the 587 NMEs. The Drugs@FDA database provided IND dates for 303 (51.6%) NMEs and the FR contributed with 297 (50.6%) IND dates. Out of the 445 NMEs for which an IND date was obtained, 274 (61.6%) had more than one date reported. DISCUSSION: Key finding of this paper is a considerable inconsistency in reliably available or reported data elements, in this particular case, IND application filing dates as assembled from publicly-available sources. CONCLUSION: Our team will continue to focus on finding ways to collect relevant information to measure impact of drug innovation.

A global perspective on assisted reproductive technology fertility treatment: an 8-country fertility specialist survey.

BACKGROUND: Procedures that may optimize success in achieving live births from assisted reproductive technology (ART) continue to be examined. Not yet considered are the perspectives of fertility specialists regarding important developments in the fertility treatment field, current unmet needs, and anticipated future advances. In the current study, an 8-country survey of fertility specialists was conducted to provide a comprehensive, global depiction of fertility treatments across different regions. METHODS: Fertility specialists from France, Germany, Italy, Spain, the United Kingdom (UK), the United States (US), China, and Japan were invited to participate in an online survey. Participants were eligible if they personally managed ≥25 patients/month who were experiencing difficulty conceiving, and if they had performed ART fertility treatment with ≥1 patient in the previous month. Quantitative questions addressed the number of patients seen, main infertility causes, number of cycles performed, ART procedure type, and ART outcomes. Qualitative questions covered diagnostic trends, unmet needs, important advances, and expected future developments. RESULTS: The number of fertility specialists who completed the survey included 29 in France, 33 in Germany, 23 in Italy, 38 in Spain, 34 in the UK, 91 in the US, 50 in China, and 65 in Japan. Patient volume increased over the prior 2 years according to 67 % (242/363) of the fertility specialists. As expected, ART outcomes all declined with age in all countries. ART outcomes varied by country, with the highest implantation, pregnancy, and live birth rates reported by fertility specialists in the US and China and the lowest rates reported in France and Italy. The most frequently reported unmet needs in fertility treatment were financial coverage, improved implantation rate, and egg donation. Most frequently named future advancements expected to change the fertility treatment field included improved embryo selection through imaging and/or metabolomics, improved embryo implantation rate, and use of preimplantation genetic diagnosis. CONCLUSIONS: This study, which follows a rigorous survey methodology, elucidates the current state of fertility specialists' practices and perspectives on the global fertility treatment field, which highlights differences and similarities among countries. This research may inform further studies and procedural developments that might better improve and standardize ART.

Evaluation of Segmentation, Rotation, and Geographic Delivery Approaches for Deployment of Multiple First-Line Treatment (MFT) to Respond to Antimalarial Drug Resistance in Africa: A Qualitative Study in Seven Sub-Sahara Countries.

BACKGROUND: Several studies recently confirmed the emergence of resistance to antimalarial drugs in sub-Saharan Africa. Multiple first-line treatment (MFT) is one of the measures envisaged to respond to the emergence and spread of this resistance. The aim of this study was to identify the perceived advantages and disadvantages of several MFT deployment strategies and to better understand potential implementation drivers and barriers. METHODS: A qualitative survey was conducted in seven sub-Saharan countries amongst key opinion leaders, national decision makers, and end users. A total of 200 individual interviews were conducted and findings were analyzed following a thematic inductive approach. RESULTS: From a policy perspective, the new MFT intervention would require endorsement at the global, national, and regional levels to ensure its inclusion in guidelines. Funding of the MFT intervention could be a bottleneck due to costs associated with additional training of healthcare workers, adaptation of drug delivery mechanisms, and higher costs of drugs. Concerning the MFT deployment strategies, a slight preference for the segmentation strategy was expressed over the rotation and geographic approaches, due to the perception that a segmentation approach is already in place at country level. CONCLUSIONS: The findings highlighted the need for a collective approach to MFT deployment through the engagement of stakeholders at all levels of malaria management.

Perception of Malaria Chemoprevention Interventions in Infants and Children in Eight Sub-Saharan African Countries: An End User Perspective Study.

Preventive chemotherapy interventions have been identified as key tools for malaria prevention and control. Although a large number of publications have reported on the efficacy and safety profile of these interventions, little literature exists on end-user experience. The objective of this study was to provide insights on the perceptions and attitudes towards seasonal malaria chemoprevention (SMC) and intermittent preventive treatment of infants (IPTi) to identify drivers of and barriers to acceptance. A total of 179 in-depth qualitative interviews were conducted with community health workers (CHWs), health center managers, parents of children receiving chemoprevention, and national decision makers across eight countries in sub-Saharan Africa. The transcribed verbatim responses were coded and analyzed using a thematic approach. Findings indicate that, although SMC is largely accepted by end users, coverage remained below 100%. The main causes mentioned were children's absenteeism, children being sick, parents' reluctance, and lack of staff. Regarding IPTi, results from participants based in Sierra Leone showed that the intervention was generally accepted and perceived as efficacious. The main challenges were access to water, crushing the tablets, and high staff turnover. SMC and IPTi are perceived as valuable interventions. Our study identified the key elements that need to be considered to facilitate the expansion of these two interventions to different geographies or age groups.

How Oncologists Perceive the Availability and Quality of Information Generated From Patient-Reported Outcomes (PROs).

BACKGROUND: Despite increased incorporation of patient-reported outcome (PRO) measures into clinical trials, information generated from PROs remains largely absent from drug labeling and electronic health records, giving rise to concerns that such information is not adequately informing clinical practice. OBJECTIVE: To evaluate oncologists' perceptions concerning the availability and quality of information generated from PRO measures. Additionally, to identify whether an association exists between perceptions of availability and attitudes concerning quality. METHOD: An online, 11-item questionnaire was developed to capture clinician perspectives on the availability and use of PRO data to inform practice. The survey also asked respondents to rate information on the basis of 4 quality metrics: "usefulness," "interpretability," "accessibility," and "scientific rigor." RESULTS: Responses were received from 298 of 1301 invitations sent (22.9% response rate). Perceptions regarding the availability of PRO information differed widely among respondents and did not appear to be linked to practice setting. Ratings of PRO quality were generally consistent, with average ratings for the 4 quality metrics between "satisfactory" and "good." A relationship was observed between ratings of PRO data quality and perceptions of the availability. CONCLUSION: Oncologists' attitudes toward the quality of information generated from PRO measures are favorable but not enthusiastic. These attitudes may improve as the availability of PRO data increases, given the association we observed between oncologists' ratings of the quality of PRO information and their perceptions of its availability.

Persisting disparities between sexes in outcomes of ruptured abdominal aortic aneurysm hospitalizations.

We sought to describe and analyze discrepancies between sexes in the outcomes of patients hospitalized for ruptured abdominal aortic aneurysms (rAAA) by conducting a retrospective analysis of the Nationwide Inpatient Sample. The review included all adult patients (≥18 years old) hospitalized with a primary diagnosis of rAAA between January 2002 and December 2014. In-hospital mortality differences between females and males were analyzed overall and separately among those receiving endovascular AAA repair (EVAR) or open AAA repair (OAR). In-hospital mortality for females declined from 61.0% in 2002 to 49.0% in 2014 (P for trend <0.001), while mortality for males declined from 48.6% in 2002 to 32.2% in 2014 (P for trend <0.001). Among those receiving EVAR, females were significantly more likely to die in the hospital than males (adjusted odds ratio [OR], 1.44; 95% CI, 1.12-1.84). In addition, the odds of mortality among those receiving OAR were higher for females than males (adjusted OR, 1.14; 95% CI: 1.00-1.31). These data provide evidence that despite overall decreasing trends in mortality for both sexes, females remain at higher risk of death compared with males regardless of surgical repair procedure.

Considerations on bringing warehoused HCV patients into active care following interferon-free, direct-acting antiviral drug approval.

OBJECTIVES: Until recently, lack of efficacious and tolerable hepatitis C virus (HCV) treatments prompted patient warehousing until better treatment options became available. We investigated whether the introduction of ledipasvir/sofosbuvir precipitated patient return to clinics, thereby changing HCV clinic dynamics. METHODS: Online questionnaire responses indicated the volume of HCV patients followed, the proportion of warehoused patients and those who were proactively offered new options, methods for identifying and contacting patients, and insurance authorization/reimbursement-related information. RESULTS: Of 168 practices surveyed, 19% indicated no patient warehousing in the previous 3 years; 81% had warehoused 40% of patients; 92% were able to handle their patient load; and 82% had not changed practices to accommodate more HCV patients in the previous 12 months. Of the 35% of patients who were ledipasvir/sofosbuvir-eligible, 50% already completed/are completing therapy, 21% were not treated due to insurance denial, and 19% were awaiting responses from insurance companies. CONCLUSIONS: Launch of a new treatment did not overburden HCV practices. Patients eligible to receive new treatments were being treated, but pre-authorization processes and reimbursement denials reduced the numbers of treated patients.

Global perspective on colonoscopy use for colorectal cancer screening: A multi-country survey of practicing colonoscopists.

OBJECTIVES: To examine colorectal cancer screening practices among colonoscopy specialists from 5 countries and inform public health needs in improvement of the ongoing global crisis in colorectal cancer. METHODS: An online survey among colonoscopy specialists was conducted in France, Germany, the United Kingdom, Japan, and the United States. The survey covered topics on colonoscopy practices in the screening as well as in the treatment setting, as well as expected trends. RESULTS: Participating colonoscopy specialists included 114 physicians from the United States, 81 from France, 80 from Germany, 80 from the United Kingdom, and 156 from Japan. Survey results revealed that 59%-73% of colonoscopies were performed in patients aged 50-75 years old, with 15%-23% performed in patients <50 years old. The proportion of patients with age-based versus symptom-based first colorectal cancer screening varied by country and age. Sedation protocols varied by country; however, rate of incomplete colonoscopy was low in all countries. The proportion of negative first colonoscopies decreased with age in all countries. CONCLUSIONS: This multi-country survey of real-world clinical practices suggests a need for improved participation in population age-based colorectal cancer screening and possibly younger age of screening initiation than currently recommended by guidelines. The variation among countries in the proportion of patients who received their first colonoscopy due to age-based colorectal cancer screening versus symptom-based initial colonoscopy indicates that population-based screening initiatives and improved health outcomes will benefit from public health awareness programs.

Variability in the therapeutic management of advanced ovarian cancer patients: a five-country survey of oncologists.

BACKGROUND: Advanced ovarian cancer patients have a poor prognosis, mainly because the disease is diagnosed at a late stage. A number of therapeutic approaches, such as neoadjuvant and maintenance therapies, have been developed to try to improve treatment outcome. In parallel, the targeted therapies bevacizumab and olaparib have recently been approved for ovarian cancer treatment. The goal of our survey was to provide a comprehensive, global depiction of advanced ovarian cancer treatments across different regions. PATIENTS AND METHODS: Oncologists from France, Italy, Germany, the UK, and the USA were invited to participate in an online survey. Participants were eligible if they personally managed at least 15 ovarian cancer patients. Quantitative questions addressed the proportion of patients in neoadjuvant, treatment, and maintenance settings; proportion of BRCA-positive patients; and the type of treatment prescribed per setting and per line of therapy, depending on the patient's BRCA status. RESULTS: A total of 138 respondents completed our survey in Europe and 132 in the USA. The proportions of patients in treatment, maintenance, and remission were identical across each country and line of treatment at 60%, 20%, and 20%, respectively. The proportion of BRCA-tested patients ranged from 45% in Italy to 73% in the USA, with 10% (UK)-21% (Italy) of tested patients having a positive status. Levels of bevacizumab and olaparib prescriptions differed based on the country, line of treatment, and setting, with a significant share of patients receiving both drugs outside of their approved indications for ovarian cancer treatment. CONCLUSION: This survey provides real-world data on how advanced ovarian cancer patients are currently treated: 1) BRCA testing was not performed systematically, which raises concerns regarding access to treatment and 2) absence of consensus regarding which chemotherapeutic regimens or targeted therapy to use in different stages of the disease.

Idiopathic pulmonary fibrosis: Physicians' perceptions of patient treatment with recently approved drugs.

Idiopathic pulmonary fibrosis (IPF) is a rare, chronic and ultimately fatal disease for which only palliative treatments existed until recently. Between 2011 and 2015, two new drugs, pirfenidone and nintedanib, were approved in the US and Europe for the treatment of IPF, providing hope for patients. The objectives of our work were to understand physicians' expected use of these new treatments in the US and Europe, and to estimate their potential. To achieve this goal, we conducted surveys amongst US and European Union (EU) pulmonologists caring for patients with IPF. There was a significant difference between EU and US physicians in the treatment of patients with mild disease with pirfenidone; the EU physicians anticipated using pirfenidone for 57% of their patients with mild disease, whereas the US pulmonologists anticipated using it for 34% of their patients (p = 0.01). Regarding patients with severe disease, the US pulmonologists anticipated treating 74% with either pirfenidone (46%) or nintedanib (28%), whereas the EU pulmonologists treated 28% with pirfenidone and anticipated treating 20% with nintedanib. These findings suggest treatment with pirfenidone and nintedanib based on disease severity may vary between US and EU physicians, which may affect patient outcomes.

Improving pharmaceutical innovation by building a more comprehensive database on drug development and use.

New drugs and biologics have had a tremendous impact on the treatment of many diseases. However, available measures suggest that pharmaceutical innovation has remained relatively flat, despite substantial growth in research and development spending. We review recent literature on pharmaceutical innovation to identify limitations in measuring and assessing innovation, and we describe the framework and collaborative approach we are using to develop more comprehensive, publicly available metrics for innovation. Our research teams at the Brookings Institution and Deerfield Institute are collaborating with experts from multiple areas of drug development and regulatory review to identify and collect comprehensive data elements related to key development and regulatory characteristics for each new molecular entity approved over the past several decades in the United States and the European Union. Subsequent phases of our effort will add data on downstream product use and patient outcomes and will also include drugs that have failed or been abandoned in development. Such a database will enable researchers to better analyze the drivers of drug innovation, trends in the output of new medicines, and the effect of policy efforts designed to improve innovation.