Health Care Regulatory Agencies Research Articles

Protocol for the development of a core outcome set for clinical trials in primary sclerosing cholangitis

BackgroundPrimary sclerosing cholangitis (PSC) is a progressive immune-mediated liver disease, for which no medical therapy has been shown to slow disease progression. However, the horizon for new therapies is encouraging,...

A “Do No Harm” Novel Safety Checklist and Research Approach to Determine Whether to Launch an Artificial Intelligence–Based Medical Technology: Introducing the Biological-Psychological, Economic, and Social (BPES) Framework

Given the impact artificial intelligence (AI)-based medical technologies (hardware devices, software programs, and mobile apps) can have on society, debates regarding the principles behind their development and deployment are emerging. Using the biopsychosocial model applied in psychiatry and other fields of medicine as our foundation, we propose a novel 3-step framework to guide industry developers of AI-based medical tools as well as health care regulatory agencies on how to decide if a product should be launched-a "Go or No-Go" approach. More specifically, our novel framework places stakeholders' (patients, health care professionals, industry, and government institutions) safety at its core by asking developers to demonstrate the biological-psychological (impact on physical and mental health), economic, and social value of their AI tool before it is launched. We also introduce a novel cost-effective, time-sensitive, and safety-oriented mixed quantitative and qualitative clinical phased trial approach to help industry and government health care regulatory agencies test and deliberate on whether to launch these AI-based medical technologies. To our knowledge, our biological-psychological, economic, and social (BPES) framework and mixed method phased trial approach are the first to place the Hippocratic Oath of "Do No Harm" at the center of developers', implementers', regulators', and users' mindsets when determining whether an AI-based medical technology is safe to launch. Moreover, as the welfare of AI users and developers becomes a greater concern, our framework's novel safety feature will allow it to complement existing and future AI reporting guidelines.

An AI-driven clinical care pathway to reduce 30-day readmission for chronic obstructive pulmonary disease (COPD) patients

Healthcare regulatory agencies have mandated a reduction in 30-day hospital readmission rates and have targeted COPD as a major contributor to 30-day readmissions. We aimed to develop and validate a simple tool deploying an artificial neural network (ANN) for early identification of COPD patients with high readmission risk. Using COPD patient data from eight hospitals within a large urban hospital system, four variables were identified, weighted and validated. These included the number of in-patient admissions in the previous 6 months, the number of medications administered on the first day, insurance status, and the Rothman Index on hospital day one. An ANN model was trained to provide a predictive algorithm and validated on an additional dataset from a separate time period. The model was implemented in a smartphone app (Re-Admit) incorporating four input risk factors, and a clinical care plan focused on high-risk readmission candidates was then implemented. Subsequent readmission data was analyzed to assess impact. The areas under the curve of receiver operating characteristics predicting readmission with ANN is 0.77, with sensitivity 0.75 and specificity 0.67 on the separate validation data. Readmission rates in the COPD high-risk subgroup after app and clinical intervention implementation saw a significant 48% decline. Our studies show the efficacy of ANN model on predicting readmission risks for COPD patients. The AI enabled Re-Admit smartphone app predicts readmission risk on day one of the patient’s admission, allowing for early implementation of medical, hospital, and community resources to optimize and improve clinical care pathways.

Colombian Consensus on the Treatment of Placenta Accreta Spectrum (PAS)

Colombian Consensus on the Treatment of Placenta Accreta Spectrum (PAS)

Role of Drone Technology Helping in Alleviating the COVID-19 Pandemic.

The COVID-19 pandemic, caused by a new coronavirus, has affected economic and social standards as governments and healthcare regulatory agencies throughout the world expressed worry and explored harsh preventative measures to counteract the disease’s spread and intensity. Several academics and experts are primarily concerned with halting the continuous spread of the unique virus. Social separation, the closing of borders, the avoidance of big gatherings, contactless transit, and quarantine are important methods. Multiple nations employ autonomous, digital, wireless, and other promising technologies to tackle this coronary pneumonia. This research examines a number of potential technologies, including unmanned aerial vehicles (UAVs), artificial intelligence (AI), blockchain, deep learning (DL), the Internet of Things (IoT), edge computing, and virtual reality (VR), in an effort to mitigate the danger of COVID-19. Due to their ability to transport food and medical supplies to a specific location, UAVs are currently being utilized as an innovative method to combat this illness. This research intends to examine the possibilities of UAVs in the context of the COVID-19 pandemic from several angles. UAVs offer intriguing options for delivering medical supplies, spraying disinfectants, broadcasting communications, conducting surveillance, inspecting, and screening patients for infection. This article examines the use of drones in healthcare as well as the advantages and disadvantages of strict adoption. Finally, challenges, opportunities, and future work are discussed to assist in adopting drone technology to tackle COVID-19-like diseases.

A Privacy-Preserving Medical Data Sharing Framework: Techniques, Applications, and Challenges

To improve patient outcomes and advance medical research, it is crucial that healthcare data are shared securely and effectively. It is difficult to communicate data while retaining confidentiality, though, due to the delicate nature of healthcare data and worries about patient privacy. Sensitive patient data must be safeguarded while facilitating secure data sharing, which calls for a framework that protects privacy. For implementing such a system, various methods like differential privacy, secure multi-party computation, and homomorphic encryption have been suggested. It is necessary to handle issues including interoperability problems, legal and ethical dilemmas, and technical difficulties. In order to create a framework for sharing medical data while protecting privacy, this study suggests a method that combines homomorphic encryption and blockchain technology. The suggested method offers a safe and effective means of exchanging and storing encrypted healthcare data while preserving data integrity and privacy. A multidisciplinary strategy combining cooperation between healthcare providers, data scientists, privacy experts, and regulatory agencies is necessary for the development and implementation of a medical data sharing framework that protects patient privacy. A privacy-preserving framework for medical data sharing can promote effective and secure data exchange for better healthcare outcomes by addressing the issues and utilizing the tools at hand.

Legal implications of antibiotic stewardship programs.

Infectious diseases professional societies, public health agencies, and healthcare regulatory agencies call for antibiotic stewardship programs (ASP) in many healthcare settings. However, medical legal implications of these programs remain largely uncharted territory. Although there is no legal precedent addressing issues of liability and standards of care on this subject, anticipating how the courts may assess questions of medical liability with respect to the various components of ASPs is important to define best practices in ASP operations, not only to manage the potential risk but also to improve patient care. This article seeks to address some of the common processes and interventions involved in antibiotic stewardship and the potential professional liability implications of these activities.

Machine Intelligence in Cardiovascular Medicine.

The computer science technology trend called artificial intelligence (AI) is not new. Both machine learning and deep learning AI applications have recently begun to impact cardiovascular medicine. Scientists working in the AI domain have long recognized the importance of data quality and provenance to AI algorithm efficiency and accuracy. A diverse array of cardiovascular raw data sources of variable quality-electronic medical records, radiological picture archiving and communication systems, laboratory results, omics, etc.-are available to train AI algorithms for predictive modeling of clinical outcomes (in-hospital mortality, acute coronary syndrome risk stratification, etc.), accelerated image interpretation (edge detection, tissue characterization, etc.) and enhanced phenotyping of heterogeneous conditions (heart failure with preserved ejection fraction, hypertension, etc.). A number of software as medical device narrow AI products for cardiac arrhythmia characterization and advanced image deconvolution are now Food and Drug Administration approved, and many others are in the pipeline. Present and future health professionals using AI-infused analytics and wearable devices have 3 critical roles to play in their informed development and ethical application in practice: (1) medical domain experts providing clinical context to computer and data scientists, (2) data stewards assuring the quality, relevance and provenance of data inputs, and (3) real-time and post-hoc interpreters of AI black box solutions and recommendations to patients. The next wave of so-called contextual adaption AI technologies will more closely approximate human decision-making, potentially augmenting cardiologists' real-time performance in emergency rooms, catheterization laboratories, imaging suites, and clinics. However, before such higher order AI technologies are adopted in the clinical setting and by healthcare systems, regulatory agencies, and industry must jointly develop robust AI standards of practice and transparent technology insertion rule sets.

Methods for Universal Authentication of Medical Devices

The need for effective means of authentication of medical devices has increased with the growing number of falsified in vitro diagnostics and devices being introduced across world markets. Such substandard products result in negative consequences ranging from harm to patients and/or failure to impart the desired clinical outcomes to a loss of public trust in healthcare providers and regulatory agencies. Herein, we discuss the growing specter of medical device falsification, related cybersecurity threats and selected novel approaches suggested for authentication.

BRCA1 and BRCA2 Gene Mutations and Colorectal Cancer Risk: Systematic Review and Meta-analysis.

Investigations of the associations with colorectal cancer have yielded conflicting results. The aim of our study was to synthesize the research on colorectal cancer risks in BRCA mutation carriers by means of a systematic review and quantitatively by means of meta-analyses overall and in subgroups of BRCA mutation carriers. We searched PubMed/MEDLINE, Embase, Cochrane, Scopus, and ProQuest Dissertation & Theses. Unadjusted odds ratios (ORs) were used to derive pooled estimates of colorectal cancer risk overall and in subgroups defined by mutation type (BRCA1 or BRCA2), cancer type (colorectal or colon cancer), study design (age-sex-adjusted or crude), and ascertainment method (ascertained or inferred genotyping). The associations were evaluated using random-effect models. All statistical tests were two-sided. Eighteen studies were included in the systematic review: five cohort studies with ascertained BRCA mutation, six cohort studies involving pedigree analysis, five case-control studies, and two kin-cohort studies. Of these, 14 were used in the meta-analysis, which revealed a statistically significant increased risk of colorectal cancer in overall BRCA mutation carriers (OR = 1.24, 95% confidence interval (CI) = 1.02 to 1.51, P = .03). In subgroup meta-analyses by BRCA type, BRCA1 mutation was associated with increased risk of colorectal cancer (OR = 1.49, 95% CI = 1.19 to 1.85, P < .001), but BRCA2 was not (OR = 1.10, 95% CI = 0.77 to 1.58, P = .61). In subgroup meta-analyses of studies reporting estimates adjusted for age and sex, an increased risk of colorectal cancer for BRCA1 (OR = 1.56, 95% CI = 1.23 to 1.98, P < .001), but not for BRCA2 (OR = 1.09, 95% CI = 0.75 to 1.58, P = .66) was observed. Analyses stratified by ascertainment method found no association between BRCA mutation and colorectal cancer risk. The meta-analysis results provide clinicians and health-care regulatory agencies with evidence of the increased risk of colorectal cancer in BRCA1 mutation carriers, but not in BRCA2.

A novel flash glucose monitoring system in patients with diabetes mellitus type 1 and 2: which are the pieces of evidence for payer decision-makers?

A rigorous health technology assessment is necessary to evaluate a new technology. However, healthcare regulatory agencies have less restrictive rules about medical devices, despite some recent warnings about this relevant matter. The evaluation should have at least two key issues, which require attention. The first one is its effectiveness, and the second one is its economic sustainability. In this paper, we deal with a novel glucose-sensing technology as a case study to examine the matter in depth. An evidence-based point of view is used to highlight this important issue.

Assessing improvement capability in healthcare organisations: a qualitative study of healthcare regulatory agencies in the UK.

ObjectivesHealthcare regulatory agencies are increasingly concerned not just with assessing the current performance of the organisations they regulate, but with assessing their improvement capability to predict their future performance trajectory. This study examines how improvement capability is conceptualised and assessed by healthcare UK regulatory agencies.DesignQualitative analysis of data from six UK healthcare regulatory agencies was conducted. Three data sources were analysed using an a priori framework of eight dimensions of improvement capability identified from an extensive literature review.SettingThe focus of the research study was the regulation of hospital-based care, which accounts for the majority of UK healthcare expenditure. Six UK regulatory agencies that review hospital care participated.ParticipantsData sources included interviews with regulatory staff (n = 48), policy documents (n = 90) and assessment reports (n = 30).InterventionNone—this was a qualitative, observational study.ResultsThis research study finds that of eight dimensions of improvement capability, process improvement and learning, and strategy and governance, dominate regulatory assessment practices. The dimension of service-user focus receives the least frequency of use. It may be that dimensions which are relatively easy to ‘measure’, such as documents for strategy and governance, dominate assessment processes, or there may be gaps in regulatory agencies’ assessment instruments, deficits of expertise in improvement capability, or practical difficulties in operationalising regulatory agency intentions to reliably assess improvement capability.ConclusionsThe UK regulatory agencies seek to assess improvement capability to predict performance trajectories, but out of eight dimensions of improvement capability, two dominate assessment. Furthermore, the definition and meaning of assessment instruments requires development. This would strengthen the validity and reliability of agencies’ assessment, diagnosis and prediction of performance trajectories, and support development of more appropriate regulatory performance interventions.

Breast Cancer Chemoprevention: A Network Meta-Analysis of Randomized Controlled Trials.

Several agents have been advocated for breast cancer primary prevention. However, few of them appear effective, the associated severe adverse effects limiting their uptake. We performed a comprehensive search for randomized controlled trials (RCTs) reporting on the ability of chemoprevention agents (CPAs) to reduce the incidence of primary breast carcinoma. Using network meta-analysis, we ranked CPAs based simultaneously on efficacy and acceptability (an inverse measure of toxicity). All statistical tests were two-sided. We found 48 eligible RCTs, enrolling 271 161 women randomly assigned to receive either placebo or one of 21 CPAs. Aromatase inhibitors (anastrozole and exemestane, considered a single CPA class because of the lack of between-study heterogeneity; relative risk [RR] = 0.468, 95% confidence interval [CI] = 0.346 to 0.634), arzoxifene (RR = 0.415, 95% CI = 0.253 to 0.682), lasofoxifene (RR = 0.208, 95% CI = 0.079 to 0.544), raloxifene (RR = 0.572, 95% CI = 0.372 to 0.881), tamoxifen (RR = 0.708, 95% CI = 0.595 to 0.842), and tibolone (RR = 0.317, 95% CI = 0.127 to 0.792) were statistically significantly associated with a therapeutic effect, which was restricted to estrogen receptor-positive tumors of postmenopausal women (except for tamoxifen, which is active also during premenopause). Network meta-analysis ranking showed that the new selective estrogen receptor modulators (SERMs) arzoxifene, lasofoxifene, and raloxifene have the best benefit-risk ratio. Aromatase inhibitors and tamoxifen ranked second and third, respectively. These results provide physicians and health care regulatory agencies with RCT-based evidence on efficacy and acceptability of currently available breast cancer CPAs; at the same time, we pinpoint how much work still remains to be done before pharmacological primary prevention becomes a routine option to reduce the burden of this disease.

Use of nicorandil is Associated with Increased Risk for Gastrointestinal Ulceration and Perforation- A Nationally Representative Population-based study.

Nicorandil is a vasodilatory drug used to relieve angina symptoms. Several healthcare products regulatory agencies have issued a warning associating the use of nicorandil and gastrointestinal (GI) ulceration. We aimed to evaluate the association between use of nicorandil and GI ulceration/perforation. A population-based cohort study involving 1 million randomly sampled participants in Taiwan’s National Health Insurance Research Database was carried out. We estimated the association between use of nicorandil and GI ulceration/perforation by a Cox proportional hazards regression model. A nicorandil-specific propensity score (PS) was also created for adjustment of 75 covariates and matching. 25.8% (183/710) of nicorandil-treated patients developed new GI ulcer events and 1.6% (20/1254) developed new GI perforation events in the three-year follow-up period, as compared to 9.3% (61,281/659,081) and 0.3% (2,488/770,537) in the general population comparator cohort. Patients treated with nicorandil were at significantly increased risk of GI ulcer (PS adjusted hazard ratio 1.43, 95% CI, 1.23 to 1.65, 6848 excess cases per 100,000 person years) or GI perforation (aHR 1.60, 95% CI 1.02–2.51, 315 excess cases per 100,000 person years) compared with the nicorandil unexposed population. Our finding may warn the clinicians to weigh the overall risk-benefit balance of nicorandil treatment in patients.

Seguridad cardiovascular de los antidiabéticos no insulínicos. Posicionamiento científico SEMERGEN

Diabetes increases the risk of both microvascular and macrovascular complications. Although reducing plasma glucose levels to recommended targets decreases the risk of microvascular outcomes, the effects of anti-diabetic drugs on macrovascular complications and cardiovascular death are of concern. In fact, it has been suggested that some anti-diabetic agents could even be harmful for cardiovascular outcomes.In this context, several health care regulatory agencies have established the need for performing clinical trials specifically designed to assess the cardiovascular safety of anti-diabetic drugs. The results of 2 clinical trials have recently been published that provide important information on the cardiovascular safety of dipeptidyl peptidase 4 (DPP-4) inhibitors.The aim of this document was to review the available evidence on the cardiovascular safety of non-insulin anti-diabetic drugs and provide practical recommendations on their use in this context.

The views of healthcare professionals, drug developers and regulators on information about older people needed for rational drug prescription.

BackgroundThe ICH E7 guideline intends to improve the knowledge about medicines in geriatric patients. As a legislative document, it might not reflect the needs of healthcare professionals. This study investigated what information healthcare professionals, regulatory agencies and pharmaceutical industries consider necessary for rational drug prescribing to older individuals.Methods and FindingsA 29-item-questionnaire was composed, considering the representation in trials, pharmacokinetics, efficacy, safety, and convenience of use in older individuals, with space for additions. Forty-three European professionals with an interest in medication for older individuals were included. In order to investigate their relevance, five items were included in a second questionnaire, with 11 control items. Median scores, differences between clinical and non-clinical respondents and response consistency were analysed. Consistency was present in 10 control items. Therefore, all items of the first questionnaire and the five additional items were analysed. Thirty-seven (86%) respondents returned the first questionnaire; 31/37 (84%) the second. Information about age-related differences in adverse events, locomotor effects, drug-disease interactions, dosing instructions, and information about the proportion of included 65+ patients was considered necessary by most respondents. Clinicians considered information significantly more important than the non-clinical respondents about the inclusion of 75+, time-until-benefit in older people, anticholinergic effects, drug-disease interactions, and convenience of use. Main study limitations are the focus on information for daily practice, while the ICH E7 guideline is a legislative document focused on market approval of a new medicine. Also, a questionnaire with a Likert scale has its limitations; this was addressed by providing space for comments.ConclusionsThis study reveals that items considered necessary are currently not included in the ICH E7 guideline. Also, clinicians’ and non-clinicians’ opinions differed significantly in 15% of the items. Therefore, all stakeholders should collaborate to improve the availability of information for the rational prescribing to older individuals.

Proceedings of the 12th national conference on anticoagulant therapy

The 12th National Conference of Anticoagulant Therapy sponsored by the Anticoagulation Forum (AC Forum) was held in Phoenix, Arizona on May 9–11, 2013. The AC Forum conference welcomed over 750 attendees allowing them an opportunity to network and learn among professional colleagues with expertise in the diagnosis and treatment of thrombotic disorders. With the ever-changing landscape of anticoagulant therapy in mind, this worthwhile conference allowed participants to get access to the most current evidence-based research on drug therapies and experience an outstanding roster of international expert speakers, whose presentations are published in these proceedings. Members were also given the opportunity to present abstracts of original research. In total, 54 abstracts were presented and they are also published in this issue of the Journal of Thrombosis and Thrombolysis. New this year, the AC Forum, in conjunction with Boston University School of Medicine Office of CME, is pleased the announce the opportunity for readers to earn. Continuing Education Credits (CME AMA PRA Category 1 Credits or ANCC Nursing Contact Hours) for those that chose to read the designated manuscripts and complete associated evaluations. The designated articles include ‘‘Assessing Bleeding Risk in Patients Taking Anticoagulants’’; ‘‘Impact of Target-Specific Oral Anticoagulants on Transitions of Care and Outpatient Care Models’’; and ‘‘Frequency of Monitoring, Non-Adherence, and Other Topics Dear to an Anticoagulation Clinic Provider’’. Please follow the instructions inside this journal for more information. Attendance at the 12th National Conference on Anticoagulant Therapy is not mandatory to participate and apply for these continuing education credits. The Anticoagulation Forum is a multidisciplinary nonprofit organization that works to improve the quality of care for patients taking antithrombotic medications. The goals of the AC Forum are to provide education and networking opportunities for health care professionals, promote the clinical application of evidence-based practice, facilitate research aimed at improving health outcomes, and inform healthcare policy, regulatory agencies, and industry about best practices. The AC Forum has over 5,500 members and represents over 1,800 anticoagulation services. In an effort to advance our mission of providing education and improving patient care, the AC Forum is proud of its new web-based program, the Anticoagulation Centers of Excellence, found at excellence.acforum.org. The site provides anticoagulation services with an opportunity to compare their practice to a rigorous set of standards of excellence in five key areas of patient care. The site also includes an exceptional, comprehensive library of anticoagulation resources including policies, procedures, guidelines, and toolkits. In addition to the Anticoagulation Centers of Excellence program, the AC Forum offers free webinar programs, a newsletter, grand rounds programs, and other educational opportunities. Please visit www.acforum.org for more information. D. A. Garcia (&) Division of Hematology, University of Washington, Seattle, WA, USA e-mail: davidg99@uw.edu

Use of objective efficacy criteria for evaluation of von willebrand factor/factor VIII concentrates

von Willebrand disease (VWD) is the most common inherited coagulation disorder and is typically treated by restoring the deficient von Willebrand factor (VWF) with exogenous VWF or by stimulating release of endogenous VWF with desmopressin. Assessment of treatment efficacy is complex because there are no standardized criteria or consistent methodology in their application. The traditionally used four-point Likert scale, with criteria that are not clearly defined or easily quantifiable, relies on a subjective rating of efficacy, and is thus open to observer bias. This article presents a novel approach to assessing efficacy of VWF replacement therapy. A new objective scoring system for assessment of the treatment efficacy of bleeding episodes (objective set of criteria for evaluation of treatment efficacy in VWD) was developed to assess a new-generation human plasma-derived VWF/coagulation factor VIII concentrate (Wilate). This manuscript analyzes the results obtained using a traditional subjective scoring system for hemostatic efficacy and compares them with results obtained when a specifically developed set of stringent objective and well defined success/failure criteria are applied in a clinical trial setting. This new assessment tool provided improved objectification of the subjective judgments obtained from the recipients of the replacement therapy. A validated tool like this could ultimately be applied to clinical comparability studies for the multiplicity of new generation replacement products, as healthcare providers, regulatory agencies, and manufacturers must now consider the additional benefits conveyed by treatment modalities, such as treatment duration, alternative dosing regimens, and treatment frequency. The objective criteria appear to be more robust and present a more conservative assessment of treatment efficacy while avoiding observer and recipient bias and inconsistencies. This new approach may be a more suitable alternative for hemostatic assessment of coagulation products in VWD patients than the currently used subjective methods.

Improving Hand Hygiene Practice Through Utilization of Automated Hand Hygiene Monitoring and Feedback Technology

Healthcare regulatory agencies identify effective hand hygiene as the single most important way to reduce infection risk, yet high levels of sustained hand hygiene compliance remain elusive in healthcare facilities. A 2010 Infection Control and Hospital Epidemiology study systematically reviewed 96 empirical studies on hand hygiene adherence and found the median for hand hygiene compliance was found to be only 40%, with 72% of the studies reporting compliance rates of 50% or less. This study describes the use of an automated hand hygiene monitoring to improve hand hygiene performance and positively affect patient perception of caregiver behavior.

ACCF/AHA 2011 Health Policy Statement on Therapeutic Interchange and Substitution

Preamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1291 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1291 1. Purpose of This Document . . . . . . . . . . . . . . .1291 2. Document Development Process . . . . . . . . . .1291 3. Definitions, Terminology, and Regulations . . .1292 1. Terminology . . . . . . . . . . . . . . . . . . . .1292 2. Generics . . . . . . . . . . . . . . . . . . . . . . . .1293 3. Bioequivalence . . . . . . . . . . . . . . . . . .1293 4. Biologics and Biosimilars. . . . . . . . . . .1294 2. Pharmacogenomics . . . . . . . . . . . . . . . . . . . . . . . .1295 3. Federal Regulations and State Laws . . . . . . . . . . .1296 4. Therapeutic Approaches . . . . . . . . . . . . . . . . . . . . .1296 1. Therapeutic Interchange . . . . . . . . . . . . . . . . .1296 2. Therapeutic Substitution . . . . . . . . . . . . . . . . .1297 3. Generic Substitution . . . . . . . . . . . …