Landscape Of Clinical Research Research Articles

Head and Neck Cancer Research Ethics: A Primer

ABSTRACT The rapidly evolving landscape of clinical research in head and neck cancer promises scientific discovery that will benefit patients and stand to improve the human condition for years to come. However, it is imperative that the head and neck oncology research community remains cognizant of the ethical conundrums posed by novel clinical investigation and respects and honors the primacy of the patients and participants upon whom such discoveries depend. It is as vital as ever to revisit the ethical debates of the past, the novel issues of the present, and potential ethical concerns of the future, to ensure research subject protection and respect evolves at the same pace as the research enterprise itself. Herein, we review the basic ethical principles required of human subjects research, the regulatory landscape, and selected emerging debates with relevant examples for head and neck providers and researchers. How to cite this article Smith JD, Spector-Bagdady K, Shuman AG. Head and Neck Cancer Research Ethics: A Primer. Int J Head Neck Surg 2017;8(2):49-56.

Business analysis for a sustainable, multi-stakeholder ecosystem for leveraging the Electronic Health Records for Clinical Research (EHR4CR) platform in Europe

IntroductionThe Electronic Health Records for Clinical Research (EHR4CR) technological platform has been developed to enable the trustworthy reuse of hospital electronic health records data for clinical research. The EHR4CR platform can enhance and speed up clinical research scenarios: protocol feasibility assessment, patient identification for recruitment in clinical trials, and clinical data exchange, including for reporting serious adverse events. Our objective was to seed a multi-stakeholder ecosystem to enable the scalable exploitation of the EHR4CR platform in Europe, and to assess its economic sustainability. Materials and methodsMarket analyses were conducted by a multidisciplinary task force to define an EHR4CR emerging ecosystem and multi-stakeholder value chain. This involved mapping stakeholder groups and defining their unmet needs, incentives, potential barriers for adopting innovative solutions, roles and interdependencies. A comprehensive business model, value propositions, and sustainability strategies were developed accordingly. Using simulation modelling (including Monte Carlo simulations) and a 5-year horizon, the potential financial outcomes of the business model were forecasted from the perspective of an EHR4CR service provider. ResultsA business ecosystem was defined to leverage the EHR4CR multi-stakeholder value chain. Value propositions were developed describing the expected benefits of EHR4CR solutions for all stakeholders. From an EHR4CR service provider’s viewpoint, the business model simulation estimated that a profitability ratio of up to 1.8 could be achieved at year 1, with potential for growth in subsequent years depending on projected market uptake. ConclusionsBy enhancing and speeding up existing processes, EHR4CR solutions promise to transform the clinical research landscape. The ecosystem defined provides the organisational framework for optimising the value and benefits for all stakeholders involved, in a sustainable manner. Our study suggests that the exploitation of EHR4CR solutions appears profitable and sustainable in Europe, with a growth potential depending on the rates of market and hospital adoption.

The Schistosomiasis Clinical Trials Landscape: A Systematic Review of Antischistosomal Treatment Efficacy Studies and a Case for Sharing Individual Participant-Level Data (IPD).

BackgroundSchistosomiasis control mainly relies on preventive chemotherapy with praziquantel (PZQ) distributed through mass drug administration. With a target of 260 million treatments yearly, reliably assessing and monitoring efficacy is all-important. Recommendations for treatment and control of schistosomiasis are supported by systematic reviews and meta-analyses of aggregated data, which however also point to limitations due to heterogeneity in trial design, analyses and reporting. Some such limitations could be corrected through access to individual participant-level data (IPD), which facilitates standardised analyses.MethodologyA systematic literature review was conducted to identify antischistosomal drug efficacy studies performed since 2000; including electronic searches of the Cochrane Infectious Diseases Group specialised register and the Cochrane Library, PubMed, CENTRAL and Embase; complemented with a manual search for articles listed in past reviews. Antischistosomal treatment studies with assessment of outcome within 60 days post-treatment were eligible. Meta-data, i.e. study-level characteristics (Schistosoma species, number of patients, drug administered, country, etc.) and efficacy parameters were extracted from published documents to evaluate the scope of an individual-level data sharing platform.Principal findingsOut of 914 documents screened, 90 studies from 26 countries were included, enrolling 20,517 participants infected with Schistosoma spp. and treated with different PZQ regimens or other drugs. Methodologies varied in terms of diagnostic approaches (number of samples and test repeats), time of outcome assessment, and outcome measure (cure rate or egg reduction rate, as an arithmetic or geometric mean), making direct comparison of published data difficult.ConclusionsThis review describes the landscape of schistosomiasis clinical research. The volume of data and the methodological and reporting heterogeneity identified all indicate that there is scope for an individual participant-level database, to allow for standardised analyses.

Life after transplant: are we becoming high maintenance in AML?

Allogeneic hematopoietic cell transplantation (allo-HCT) for patients with AML is increasingly able to impact the historically poor outcomes in this disease. Nonetheless, even with transplant, the rates of post-HCT relapse are unacceptably high, and remain a great challenge in the treatment of patients with AML. Maintenance therapies after allo-HCT, given to patients at high risk of relapse or with evidence of minimal residual disease (MRD), may provide a way to reduce relapse rates and improve survival. New therapies may offer acceptable toxicity profiles in the post-HCT setting, and investigations are ongoing using hypomethylating agents, histone deacetylase inhibitors, immunomodulatory drugs, targeted tyrosine kinase inhibitors, drug-antibody conjugates and cellular therapies. Future directions in the field of post-HCT therapies may include better risk stratification with MRD, as well as the exploitation of novel mechanisms such as immune checkpoint inhibition and modified chimeric antigen receptor (CAR) T cells. In this mini review, we discuss the current landscape of clinical research in post-HCT maintenance therapies, as well as future therapeutic strategies of interest. Although there is great potential for post-HCT agents to improve AML outcomes, these will need to be evaluated prospectively through well-designed randomized clinical trials.

Idiopathic pulmonary fibrosis: Recent advances on pharmacological therapy

Idiopathic pulmonary fibrosis (IPF) is the most common and lethal of the idiopathic interstitial pneumonias with an estimated 5-year survival of approximately 20%. In the last two decades our understanding of disease pathogenesis has substantially evolved and novel compounds have been developed consequent to the increasing knowledge of the mechanisms underlying disease pathobiology. The disease appears to be driven - following chronic injury - by abnormal/dysfunctional alveolar epithelial cells that promote fibroblast recruitment and proliferation, resulting in scarring of the lung and irreversible loss of function. With very few exceptions, clinical trials evaluating novel potential therapies have provided disappointing results. More recently, pirfenidone and nintedanib, two compounds with pleiotropic mechanisms of action, have proven effective in slowing functional decline and disease progression in IPF patients with mild to moderate functional impairment, highlighting the importance of timely diagnosis and administration of treatment in early stages of disease. However, due to the complexity and uncertainties intrinsic to IPF, it is essential that each therapeutic strategy be tailored to the individual patient, after evaluation of potential benefits and risks. This article provides an overview of the most recent clinical trials in IPF and discusses how their results are going to change the clinical and clinical research landscape in IPF. A number of agents with high potential are currently being tested and many more are ready for clinical trials. Their completion is critical for achieving the ultimate goal of curing patients with IPF.

Cutting the cord from myelodysplastic syndromes: chronic myelomonocytic leukemia-specific biology and management strategies.

Chronic myelomonocytic leukemia (CMML) is a troublesome hematologic malignancy characterized by peripheral blood monocytosis, marrow dysplasia, cytopenias, frequent extramedullary involvement by clonal cells, and a propensity for progression to acute myeloid leukemia. Although previously considered a subtype of the myelodysplastic syndromes (MDS), CMML is now recognized as a distinct entity with unique biologic and clinical features. This change has created a scientific and clinical research landscape that makes it difficult to discern CMML-specific validated conclusions versus speculative extrapolation from more general MDS data. Here, we review recent biologic observations that support the current CMML WHO classification, such as the high frequency of SRSF2 and ASXL1 mutations compared with MDS and critical dependence of CMML cells on granulocyte-macrophage colony-stimulating factor signaling. In addition, we discuss CMML-specific prognostic tools and therapeutic results of agents developed for MDS in patients with CMML. The present review focuses on evidence supporting CMML ontology and identifies key clinical differences in the management of CMML and that of MDS subtypes.

An Analysis of Information Technology Adoption by IRBs of Large Academic Medical Centers in the United States.

The clinical research landscape has changed dramatically in recent years in terms of both volume and complexity. This poses new challenges for Institutional Review Boards' (IRBs) review efficiency and quality, especially at large academic medical centers. This article discusses the technical facets of IRB modernization. We analyzed the information technology used by IRBs in large academic institutions across the United States. We found that large academic medical centers have a high electronic IRB adoption rate; however, the capabilities of electronic IRB systems vary greatly. We discuss potential use-cases of a fully exploited electronic IRB system that promise to streamline the clinical research work flow. The key to that approach utilizes a structured and standardized information model for the IRB application.

European perspective for effective cancer drug development

Health systems and the clinical research landscape evolve continuously owing to increased risk aversion, scrutiny by funding bodies, and costs of clinical trials. In this context, however, current drug development procedures are far from optimal, as exemplified by the late-stage failure of several drugs. The identification of new drugs urgently requires approaches based on a solid understanding of cancer biology, and that will support the design of robust confirmatory trials. The complexity and the costs of drug development are now beyond the knowledge and operational capacity of single organisations, therefore, a drastic deviation from the traditional path of drug discovery and new forms of multidisciplinary partnerships are needed to succeed in this sector. The European Organisation for Research and Treatment of Cancer (EORTC) proposes the use of collaborative molecular screening platforms (CMSPs) as a new approach to tackle this issue. These CMSPs have the advantage of optimizing the expertise of several partners and combining efforts alongside with cost-sharing models for efficient patient selection. This article describes some of the challenges to advancing drug development and improving medical treatments and how these hurdles can be overcome.

Issues in clinical research for metastatic breast cancer

Technical advances and progresses in tumor biology hold promise for the advent of new anticancer agents. These changes are impacting the conduct and design of clinical trials. This review describes the changing landscape of clinical research in metastatic breast cancer (MBC). Clinical trials in breast cancer that started between 2007 and 2011 were analyzed. In the metastatic setting, 72% (n = 479) of these studies evaluated targeted therapies and 21% (n = 139) conventional treatments. During this period, the number of phase II trials decreased over time, whereas biology-driven studies, although small in terms of absolute number, now represent 15% of the total. Nevertheless, genomic segments are too rare to allow conventional drug development and require changes in the way clinical trials are being done. Several options are being explored to address this challenge: develop large consortium, perform molecular screening in larger populations, develop clinical trials testing algorithm for treatment decision, and no longer drugs. The landscape of clinical research in MBC is changing with the development of molecular medicine. Research institutions and cooperative groups will need to adapt to this changing landscape in clinical research.

How can innovative forms of clinical research contribute to deliver affordable cancer care in an evolving health care environment?

As health care costs are constantly rising and governments are reforming their healthcare systems there is an urgent need to reshape the European clinical research landscape. To bridge the translational gap extensive research to understand the mechanism of the agents and of the disease has to be performed and the real benefit of drugs needs to be assessed independently. Furthermore, meaningful data for reimbursement strategies will be a major goal of future clinical trials as well.Therefore, a new integrated model of clinical cancer research is needed to optimise the R&D process. Strategies to ensure that we can gather robust and relevant data about the effectiveness of various healthcare interventions have to be developed to provide optimal patient care within the limits of a healthcare budget.

The role of comparative effectiveness research in transfusion medicine clinical trials: proceedings of a National Heart, Lung, and Blood Institute workshop

Comparative effectiveness research (CER) is the study of existing treatments or ways to deliver health care to determine what intervention works best under specific circumstances. CER evaluates evidence from existing studies or generates new evidence, in different populations and under specific conditions in which the treatments are actually used. CER does not embrace one research design over another but compares treatments and variations in practice using methods that are most likely to yield widely generalizable results that are directly relevant to clinical practice. Treatments used in transfusion medicine (TM) are among the most widely used in clinical practice, but are among the least well studied. High-quality evidence is lacking for most transfusion practices, with research efforts hampered by regulatory restrictions and ethical barriers. To begin addressing these issues, the National Heart, Lung, and Blood Institute convened a workshop in June 2011 to address the potential role of CER in the generation of high-quality evidence for TM decision making. Workshop goals were to: 1) evaluate the current landscape of clinical research, 2) review the potential application of CER methods to clinical research, 3) assess potential barriers to the use of CER methodology, 4) determine whether pilot or vanguard studies can be used to facilitate planning of future CER research, and 5) consider the need for and delivery of training in CER methods for researchers.

Pharmaceutical Medicine in Germany

Pharmaceutical Medicine has a long-standing history in Germany, but is still not yet a legitimate subspecialty of medicine according to the official list of medical specialities issued by the German Medical Association. This short article provides background information on the German Association of Pharmaceutical Medicine and addresses key points of the current landscape of clinical research in Germany.

The Acupuncture Trialists— Collaboration: Individual Patient Data Meta-Analysis of Chronic Pain Trials

The purpose of clinical trials of acupuncture is to help clinicians and patients make decisions about treatment. But using acupuncture trials to aid clinical decisions is not straightforward. Take the case of a patient consulting an evidence-based physician for chronic low back pain and asking whether acupuncture might be of value. The doctor searches MEDLINE and, as of May 2009, finds 65 English-language randomised trials. Even if the doctor were to obtain copies of all of these trials, he or she would find that the results were inconsistent. Some report acupuncture to be superior to sham (placebo) acupuncture1 while others show evidence that acupuncture is superior to no treatment but not sham2 and still others conclude that acupuncture is no better than usual care.3 Clearly what is needed is a meta-analysis to synthesise the results from the different studies. Indeed, many meta-analyses of acupuncture for chronic pain have been published. These studies have tended to come to somewhat indeterminate conclusions, such as “there is limited evidence that acupuncture is more effective than no treatment for chronic pain; and inconclusive evidence that acupuncture is more effective than placebo”.4 This appears to be because, until recently, acupuncture research was dominated by small trials of questionable quality. The landscape of clinical acupuncture research has recently been dramatically altered by the publication of several large, high quality trials. These include the two NHS funded trials of acupuncture chronic headache disorders (n = 401)5 and back pain (n = 241)6 and the German Acupuncture Randomised Trials (ART) studies2 7 8 9 which randomised 300 patients each in four separate trials on osteoarthritis, chronic low back pain, migraine and chronic tension headache. But even these trials are dwarfed by the German Acupuncture (GERAC) trials which accrued close to 1000 patients each in trials …

Scrutinizing the Clinical Trials Process for Improved Patient Protection—A New Role for Applied Anthropologists?

With the recent extraordinary move by pharmaceutical giant Merck to pull its top-selling drug Vioxx from the worldwide market, the importance of protecting the public from potentially serious drug related side effects has taken center stage. As the news media highlights the cardiac dangers for patients taking COX-2 inhibitors, it has become apparent that clinical research around the world is in need of more methodological rigor. Clinical research could be enhanced if the contributions and divergent thought processes of field based disciplines are included in the development of these research protocols. As this global debate ensues, it is timely to consider how anthropologists can take a more active role to improve the design, execution, and coordination of clinical trials domestically and abroad. Recently, the Society for Medical Anthropology has advocated that anthropologists participate in shaping the ethical landscape of basic, applied, and clinical research. In an article called, "Bioethics and Anthropology: A Call for partnership." Kathleen M. MacQueen, Ph.D., MPH raises the important question: "How do we protect against exploitation without unduly constraining much needed health research that could, in fact, benefit vulnerable populations?"

The changing landscape of breast cancer clinical research: ESMO-Award lecture, ECCO-9 Hamburg, 18 September 1997

Clinical research for breast cancer is moving in three new directions following: 1) a critical analysis of three decades of randomized clinical trials for early disease; 2) increasing awareness of this lethal disease among women, generating women's associations which are pressing for improved breast cancer education, screening and treatment; 3) an exponential growth in our understanding of breast cancer molecular biology, leading to a number of innovative therapies with new targets in the cancer cell or its environment. It is the remarkable work of the Oxford Group which has finally vindicated the use of our three main weapons against breast cancer micro-metastases, namely tamoxifen, chemotherapy and ovarian ablation. There is now consensus that clinical research in the adjuvant setting may gain speed and efficiency through intergroup collaboration. Such an 'Intergroup' has been recently created in Europe and will collaborate with the American-Canadian Intergroup. Women's associations have only recently stepped forward to demand better care, and more effective therapies: they are becoming new partners in identifying critical issues in breast cancer research. Medical oncologists involved in breast cancer research are facing a new challenge: the optimal integration of traditional breast cancer therapies, namely endocrine treatments and chemotherapy, and entirely new strategies targeting signal transduction, apoptosis or angiogenesis. In view of the above, there is no doubt that we are entering a new and exciting era in breast cancer clinical research.

1284 - The changing landscape of breast cancer clinical research

1284 - The changing landscape of breast cancer clinical research