Academic literature on the topic 'Multi-site clinical trials'

6619 Background: Current methods to assess trial sites for clinical trial participation are onerous, with unnecessary redundancies and “no-value” steps that impact clinical trial participation. This project assessed the impact of current sponsor and contract research organizations (CRO) methods to evaluate sites for trials. Methods: A survey was conducted with community- and academic-based trial sites. Samples of feasibility questionnaires (FQs) used by sponsors and CROs were also compiled. An ASCO sponsored multi-stakeholder meeting was held to identify strategies to more effectively assess trial sites. Results: 113 oncology practices (63 community, 50 academic) reported completing 11 FQs and 4 pre-study site visits (PSV) on average per month. On average, each FQ took 4 hours (528 hours/site and 59,664 hours for all respondents, annually) and each PSV took 10 hours (480 hours/site and 54,240 hours for all respondents, annually) to complete. Thus, the total staff hours required to complete site feasibility assessments was 113,904 annually. Respondents reported that content in both FQs (82%) and PSVs (91%) was redundant to information previously provided and FQs were redundant between different sponsors (86%). The 42 sample FQs had a median 45 questions (range 13 to 96). Respondents noted that sponsors/CROs provided insufficient study documentation to accurately complete FQs. It took 7 months on average from first contact to first patient enrolled. Respondents also provided feedback about standardizing and streamlining site qualification processes. Conclusions: The current methods of assessing site feasibility for clinical trials poses tremendous burden on site resources and is not sustainable. New methods are needed that standardize, harmonize, and streamline criteria and site assessments. Such changes will reduce burden and costs for all stakeholders, and will expedite and increase patient enrollment onto clinical trials.

Abstract The Accrual to Clinical Trials (ACT) network is a federated network of sites from the National Clinical and Translational Science Award (CTSA) Consortium that has been created to significantly increase participant accrual to multi-site clinical trials. The ACT network represents an unprecedented collaboration among diverse CTSA sites. The network has created governance and regulatory frameworks and a common data model to harmonize electronic health record (EHR) data, and deployed a set of Informatics for Integrating Biology and the Bedside (i2b2) data repositories that are linked by the Shared Health Research Information Network (SHRINE) platform. It provides investigators the ability to query the network in real time and to obtain aggregate counts of patients who meet clinical trial inclusion and exclusion criteria from sites across the United States. The ACT network infrastructure provides a basis for cohort discovery and for developing new informatics tools to identify and recruit participants for multi-site clinical trials.

Background Travel burden often substantially limits the ability of individuals to participate in clinical trials. Wide geographic dispersion of individuals with rare diseases poses an additional key challenge in the conduct of clinical trials for rare diseases. Novel technologies and methods can improve access to research by connecting participants in their homes and local communities to a distant research site. For clinical trials, however, understanding of factors important for transition from traditional multi-center trial models to local participation models is limited. We sought to test a novel, hybrid, single- and multi-site clinical trial design in the context of a trial for Juvenile Neuronal Ceroid Lipofuscinosis (CLN3 disease), a very rare pediatric neurodegenerative disorder. Methods We created a “hub and spoke” model for implementing a 22-week crossover clinical trial of mycophenolate compared with placebo, with two 8-week study arms. A single central site, the “hub,” conducted screening, consent, drug dispensing, and tolerability and efficacy assessments. Each participant identified a clinician to serve as a collaborating “spoke” site to perform local safety monitoring. Study participants traveled to the hub at the beginning and end of each study arm, and to their individual spoke site in the intervening weeks. Results A total of 18 spoke sites were established for 19 enrolled study participants. One potential participant was unable to identify a collaborating local site and was thus unable to participate. Study start-up required a median 6.7 months (interquartile range = 4.6–9.2 months). Only 33.3% (n = 6 of 18) of spoke site investigators had prior clinical trial experience, thus close collaboration with respect to study startup, training, and oversight was an important requirement. All but one participant completed all study visits; no study visits were missed due to travel requirements. Conclusions This study represents a step toward local trial participation for patients with rare diseases. Even in the context of close oversight, local participation models may be best suited for studies of compounds with well-understood side-effect profiles, for those with straightforward modes of administration, or for studies requiring extended follow-up periods.

11527 Background: Randomized controlled trials (RCTs) in oncology, which often establish the standard of care for cancer patients, do not necessarily enroll trial participants representative of the broader patient population. We sought to characterize age disparities for cancer patients enrolled on RCTs, and asked whether certain trial-related factors (such as industry sponsorship) predispose trials to larger age disparities between trial enrollees and the general population. Methods: All phase 3 RCTs in clinical oncology with results available were identified through ClinicalTrials.gov. Only randomized multi-arm trials assessing a therapeutic intervention for cancer patients were included. The scope of trials was limited to breast, colorectal, lung, and prostate disease sites. Trial participant median ages were compared to national SEER data for population median ages by disease site. Results: Three-hundred and two trials met inclusion criteria. For all trials, the trial median age was an average 6.23 years younger than the population median age (95% CI: -5.55 to -6.91 years, p < 0.001). Trials with industry sponsorship had significantly younger trial patient populations compared with non-industry-sponsored trials (mean difference from population -6.57 vs -4.48 years, p = 0.02). Younger patients were enrolled on trials evaluating targeted agents (p = 0.04), superiority-design trials (p = 0.02), and trials utilizing a surrogate primary endpoint (p = 0.03). By disease site, lung cancer trials enrolled the youngest patients relative to the population median (-8.98 years), followed by breast (-7.76 years), colorectal (-6.96 years), and prostate (+2.66 years, p < 0.001). Conclusions: Industry-funded clinical trials are associated with larger age disparities among trial participants; we believe this represents a novel finding both in clinical oncology and academic medicine more broadly. Underrepresentation of older patients on RCTs has major ramifications for the generalizability of results as well as equity of access to care; future efforts to address trial participant age disparities may focus on those trials at greatest risk for disparities based on the identified risk factors, including industry sponsorship.

Abstract Introduction Acute respiratory infections (ARI) result in substantial annual morbidity among military personnel and decrease operational readiness. Herein, we summarize the research efforts of the Infectious Disease Clinical Research Program (IDCRP) related to ARIs. Methods The ARI Research Area of the IDCRP was established in response to the 2009 emergence of pandemic influenza A/H1N1. That year, IDCRP investigators deployed the ARI Consortium Natural History Study (ARIC NHS), a multi-centered, longitudinal observational study to assess etiology, epidemiology, and clinical characteristics of influenza-like illness (ILI) and severe acute respiratory infections (SARI) in the U.S. military. The success of this initial effort spurred implementation of several new initiatives. These include the FluPlasma trial, designed to evaluate the efficacy of hyperimmune anti-influenza plasma for the treatment of severe influenza; the self-administered live-attenuated influenza vaccine (SNIF) trial, which assessed the immunogenicity and acceptance of a self-administered live-attenuated influenza vaccine in military personnel; the Study to Address Threats of ARI in Congregate Military Populations (ATARI), a prospective study of ILI transmission, etiology and epidemiology in recruits; and the Flu Breath Test (FBT) study, a preliminary study of exhaled volatile organic compounds (VOC) in influenza patients. In addition, the InFLUenza Patient-Reported Outcome (FLU-PRO) survey, a daily diary to measure influenza symptoms during clinical trials, was developed. Lastly, the Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED) study, a two-year randomized trial designed to compare the effectiveness of the three types of licensed vaccines, launched in Fall 2018. Results The on-going ARIC NHS has enrolled over 2000 ILI and SARI cases since its inception, providing data on burden and clinical manifestations of ARI in military personnel and their families. The FluPlasma 2 trial concluded subject enrollment in 2018. Preliminary results from ATARI study show a high frequency of respiratory viruses circulating during the first two weeks of recruit training. Based on assessment of FLU-PRO responses, which were found to be reliable and reproducible, the survey may be a useful tool in clinical trials and epidemiological studies. The Flu Breath Study will complete enrollment in 2019. Findings from PAIVED are intended to provide evidence needed for assessing influenza vaccination policy in the military. Conclusions The ARI burden in the armed services remains significant every year and the threat is dynamic given emergent and evolving threats, such as influenzas. With strong successes to date, future initiatives of the ARI Research Area will focus on interventional studies, ARI transmission dynamics in congregate military settings, and determinants of risk of pandemic influenza and other emergent respiratory viruses.

Background: Racial/ethnic minority groups remain underrepresented in clinical trials. Many strategies to increase minority recruitment focus on minority communities and emphasize common diseases such as hypertension. Scant literature focuses on minority recruitment to trials of less common conditions, often conducted in specialty clinics and dependent on physician referrals. We identified trust/mistrust of specialist physician investigators and institutions conducting medical research and consequent participant reluctance to participate in clinical trials as key-shared barriers across racial/ethnic groups. We developed a trust-based continuous quality improvement intervention to build trust between specialist physician investigators and community minority-serving physicians and ultimately potential trial participants. To avoid the inherent biases of non-randomized studies, we evaluated the intervention in the national Randomized Recruitment Intervention Trial (RECRUIT). This report presents the design of RECRUIT. Specialty clinic follow-up continues through April 2017. Methods: We hypothesized that specialist physician investigators and coordinators trained in the trust-based continuous quality improvement intervention would enroll a greater proportion of minority participants in their specialty clinics than specialist physician investigators in control specialty clinics. Specialty clinic was the unit of randomization. Using continuous quality improvement, the specialist physician investigators and coordinators tailored recruitment approaches to their specialty clinic characteristics and populations. Primary analyses were adjusted for clustering by specialty clinic within parent trial and matching covariates. Results: RECRUIT was implemented in four multi-site clinical trials (parent trials) supported by three National Institutes of Health institutes and included 50 associated specialty clinics from these parent trials. Using current data, we have 88% power or greater to detect a 0.15 or greater difference from the currently observed control proportion adjusting for clustering. We detected no differences in baseline matching criteria between intervention and control specialty clinics (all p values > 0.17). Conclusion: RECRUIT was the first multi-site randomized control trial to examine the effectiveness of a trust-based continuous quality improvement intervention to increase minority recruitment into clinical trials. RECRUIT’s innovations included its focus on building trust between specialist investigators and minority-serving physicians, the use of continuous quality improvement to tailor the intervention to each specialty clinic’s specific racial/ethnic populations and barriers to minority recruitment, and the use of specialty clinics from more than one parent multi-site trial to increase generalizability. The effectiveness of the RECRUIT intervention will be determined after the completion of trial data collection and planned analyses.

The body of work presented here is a compendium of the multiple steps required for an investigator initiated trial of an existing medication (Valproic Acid- VPA) for a new indication (Retinitis Pigmentosa – RP). The chapters are listed in logical and chronological order of the process. In order to access patient records an expedited Institutional Review Board (IRB) application for retrospective chart review was submitted (Chapter 1). These records enabled the statistical analysis which not only laid the framework for the trial design, but also became the basis for two manuscripts (Chapter 2). Protocol development informed by the preliminary human studies (Chapter 3) was an instrumental part of the Investigational New Drug (IND) application (Chapter 3.5). This protocol along with the extensive case report forms that detail the intended data to be collected are included in the IND application. Because the Phase II clinical trial proposed attempting to identify the specific RP mutations of the subjects utilizing a National Eye Institute (NEI) study that enabled free genotyping services, two IRB applications were submitted (Chapter 3.6). The first was for approval of the NEI genotyping protocol, the second involved the VPA intervention. Two very different sources of funding for this trial were attempted (Chapter 4) – the NIH via the Challenge Grant mechanism and a private eye disease foundation (Foundation Fighting Blindness). In Chapter 5 I detail the alternate study designs that were considered and developed for this trial (and ultimately abandoned). Finally, in Chapter 6, I formally detail my suggestions to aid in the development of a comprehensive investigator initiated core facility at UMMMC. The goal of this project was two-fold. The first was to learn the entire process of trial and protocol design both from a Umass Institutional perspective as well as from the perspective of the FDA. The second goal was the very real prospect of helping patients with a blinding disease. This work was successful on both counts. IRB approval was received for all the submitted applications. The complexity and uniqueness of many aspects of these submissions culminated in a comprehensive learning experience. The process of working with the Umass Research Pharmacy as well as developing the industry contacts and know-how to develop a workable and financially feasible placebo were both particularly important learning experiences. FDA approval of the IND submission was also received, and the process of pre-communication and delving into the considerable and ever-changing rules and regulations resulted in an extensive and valuable knowledge base. While the practicality of funding has limited the ability of this trial to move forward at this point, given the extensive framework laid by this body of work, we are actively pursuing other opportunities. The third outcome of this work, while not as intentional, was the considerable process of determining the specific competencies and infrastructure that exist at UMMMC to enable investigator initiated drug intervention studies. While this institution is clearly moving rapidly in the direction of translational research, the many needs of these studies are often only clearly understood when the process is specifically undertaken. In completing the approval of this Phase II clinical trial, I was not only able to better understand and define the existing capabilities of UMMMC for this kind of research, I was able to add to that infrastructure when the existing knowledge or skill set was not available. In this manner, I was able to inform and guide many of the support personnel who guided me and have become a part of the strategic direction of UMMMC towards clinical translational research.

Response-Adaptive (RA) designs are used to adaptively allocate patients in clinical trials. These methods have been generalized to include Covariate-Adjusted Response-Adaptive (CARA) designs, which adjust treatment assignments for a set of covariates while maintaining features of the RA designs. Challenges may arise in multi-center trials if differential treatment responses and/or effects among sites exist. We propose Site-Adjusted Response-Adaptive (SARA) approaches to account for inter-center variability in treatment response and/or effectiveness, including either a fixed site effect or both random site and treatment-by-site interaction effects to calculate conditional probabilities. These success probabilities are used to update assignment probabilities for allocating patients between treatment groups as subjects accrue. Both frequentist and Bayesian models are considered. Treatment differences could also be attributed to differences in social determinants of health (SDH) that often manifest, especially if unmeasured, as spatial heterogeneity amongst the patient population. In these cases, patient residential location can be used as a proxy for these difficult to measure SDH. We propose the Location-Adjusted Response-Adaptive (LARA) approach to account for location-based variability in both treatment response and/or effectiveness. A Bayesian low-rank kriging model will interpolate spatially-varying joint treatment random effects to calculate the conditional probabilities of success, utilizing patient outcomes, treatment assignments and residential information. We compare the proposed methods with several existing allocation strategies that ignore site for a variety of scenarios where treatment success probabilities vary.

This thesis investigated how the National Mutual Acceptance (NMA) model of single ethical review has currently impacted, and how it is likely to impact the future, on the research governance practices of public healthcare agencies participating in multi-site clinical trials. This study sought to describe the variables associated with the impact of the NMA through the theory of Institutional Isomorphism proposed by DiMaggio and Powell , which proposes that comparable organisations develop similarities in order to appear legitimate to their stakeholders. Consolidation is influenced by: coercive isomorphism, which involves pressures from other entities on which they are dependent; mimetic isomorphism, which refers to the tendency of an organisation to imitate a more successful organisation; and normative isomorphism, which is driven by professional pressures. Data was collected in two phases. Phase One focused on the collection of quantitative data relating to perceptions of the importance of research and the impact of the NMA. Phase Two involved collection of qualitative data to explore the reasons behind current irregularities in the NMA and expectations of the future. Although participants agreed that the NMA could provide isomorphic pressures, there were concerns regarding bureaucratic inconsistency that created uncertainty in the processes. The strongest isomorphic influence provided by the NMA was coercive pressure, which was also identified as a possible future mechanism. In contrast to findings in other literature, neither mimetic nor normative pressures were perceived as influential because emphasis on the practices of individual agencies prevented a coherent system from developing. The study made three contributions to Institutional Isomorphism theory. It identified the importance of robust coercive forces to allowing mimetic and normative forces to emerge. It also highlighted the need for agencies to recognise implications of research governance beyond their own organisational boundaries and the need to quantify the responsibilities of governance personnel to strengthen coercive impact. Recommendation included the need to address: organisational leadership of the NMA, to strengthen the knowledge base through education and training, the development of a stakeholder engagement framework and opportunities to expand the NMA. This research provides new insight into understanding research governance in the context of the Australian public healthcare sector and provides a model though which further exploration may be undertaken.

碩士
臺北醫學大學
醫務管理學研究所
96
This study mainly discusses the obstacles that research nurses of TCOG face when execute multi-center clinical trials, and in the end to give away suggestions to advance organizational development and performance of the nurses from the perspective of organization, process, and human resource management. We utilize qualitative research methodology. Firstly, we set interview guidelines, including how nurses perceive the way hospital and staff interacts with them, the operation obstacles, and their career planning. Secondly, we interview 11 research nurses and transcribe the content to transcripts. Thirdly, we analyze the content through grounded theory to explore the code and construct on the issues. In order to successfully complete their jobs, research nurses of TCOG consume their energy and patience on hospital’s complex administrative system, exercise their interpersonal impact to finish jobs, supply available information to medical staff, advocate patient’s right to support their terminal lives, complete mass paper work to assure the quality of trial, give concern and suggestion to TCOG and roles of nurses, and continuous learning to assure their competency. This study focuses on three perspectives of organization, process and human resource management. Organization perspective includes the policy of government and hospital, and how nurses evaluate the strategies now hospital utilizing. And the restructuring of TCOG on replaced diseases committees by study working groups, replaced member hospitals by collaborate hospitals, create Protocol Review Committee to improve review procedure. Process perspective includes the quality maintenance of case data. It needs to build standard operation procedure on patient out of reach, review and improve the operation of case follow up, and create monitor operation to guarantee the requirement of data quality assurance. Due to analyze work lording of research nurses, the most important task is to build their job description by protocols and sites. To ensure case report forms are designed to be as relevant and reasonable as possible, it is necessary to have research nurses’ involved in the planning of protocol. Human resource perspective includes the effective support and assistance from TCOG, human resource management and on-job-training program. In order to achieve effective support to research nurses, it also needs to build coordinator’s job description by protocols and evaluate manpower demanding accordingly. An activity can be feasible immediately to heighten the interest and involvement of research nurses is to change the pattern of nurse meeting. The application of group meeting assists coordinators getting better understanding the practice of certain hospital, promotes the communication between TCOG executive and research nurses, provides research nurses a space to discuss the research topics basis on their professional on oncology nursing. To approach an attractive work environment and long-term career opportunities, TCOG should provide funds for the research nurses to attend a major meeting of oncology nursing and when they are involved with an abstract or poster being presented. Research nurses play an important role of clinical trial because they are the one to connect and fully utilize resources. Executive of TCOG faces the biggest challenge how to plan and motivate these nurses, and ultimately improve the quality and efficiency of clinical trial under restricted resources.

The Manual of Infection Prevention and Control provides practical guidance on all aspects of healthcare-associated infections (HAIs). It outlines the basic concepts of infection prevention and control (IPC), modes of transmission, surveillance, control of outbreaks, epidemiology, and biostatistics. The book provides up-to-date advice on the triage and isolation of patients and on new and emerging infectious diseases, and with the use of illustrations, it provides a step-by-step approach on how to perform hand hygiene and how to don and take off personal protective equipment correctly. In addition, this section also outlines how to minimize cross-infection by healthcare building design and prevent the transmission of various infectious diseases from infected patients after death. The disinfection and sterilization section reviews how to risk assess, disinfect and/or sterilize medical items and equipment, antimicrobial activities, and the use of various chemical disinfectants and antiseptics, and how to decontaminate endoscopes. The section on the prevention of HAIs reviews and updates IPC guidance on the prevention of the most common HAIs, i.e. surgical site infections, infections associated with intravascular and urinary catheters, and hospital- and ventilator-acquired pneumonias. In view of the global emergence of antimicrobial resistance to the various pathogens, the book examines and provides practical advice on how to implement an antibiotic stewardship programme and prevent cross-infection against various multi-drug resistant pathogens. Amongst other pathogens, the book also reviews IPC precautions against various haemorrhagic and bloodborne viral infections. The section on support services discusses the protection of healthcare workers, kitchen, environmental cleaning, catering, laundry services, and clinical waste disposal services.

Deep brain stimulation (DBS) of the subcallosal cingulate cortex (SCC) has potential as a therapeutic intervention for patients with severe treatment-resistant depression (TRD). This chapter reviews the evolution of the research support for SCC DBS. It begins with a key publication that posited a putative neural circuit hypothesis for depression and TRD; this line of research culminated in identification of the SCC as a key node involved in the antidepressant response to somatic interventions. The clinical testing of SCC DBS is then reviewed, from the first proof-of-concept study up to a large, multi-site, randomized clinical trial. The next steps in SCC DBS research are then highlighted via a focus on two papers that describe the development and early testing of a circuit-based, imaging-guided approach to SCC DBS for TRD.

Chapter 8 provides examples of programs developed to optimize retention in HIV care that are based on principles of motivational interviewing (MI). Two programs are highlighted: iEngage, a recently evaluated intervention to promote early retention in HIV-care as part of a multi-site clinical trial, and 60-Mintues for Health, a piloted intervention approach for patients tenuously engaged in HIV-care. These programs, their theoretical underpinnings, and use of MI offer some importance insights about mobilizing MI in the context of HIV care. Consistent with MI, both programs are founded on patients’ autonomy and self-determination, with the interventionist acting as a guide to help patients achieve tailored goals while avoiding the righting-reflex and highlighting change talk.

The results of basic and translational research of the Department of Biomedical Research and Technology of Irkutsk Scientific Center of the Siberian Branch of the Russian Academy of Sciences in 2012–2016 The paper presents the results of interdisciplinary research carried out in 2012–2016. The review includes the study of molecular mechanisms of pathogenesis of reparative regeneration, experimental substantiation of methods of diagnosis and prognosis of systemic disturbances of regeneration process, carrying out clinical trials of medicinal products and the formation of observational studies in the field of personalized medicine, the preparation of practical recommendations on the testing of previously developed surgical methods of prevention or correction of postoperative recovery disorders. New data are obtained on the role of the MAP-kinase cascade in the process of regeneration of muscle tissue. It has been established, that with a significant increase of VEGF concentration at the site of the repair of ischemic myocardium, progenitor cells with the CD34+CD45+ phenotype appear, which opens up prospects for the development of biotechnology to restore the damaged myocardium with its own pool of progenitor cells. The new data on the role of growth factors in the post-infarction remodeling are found. It has been revealed, that in local increase of selenium concentration low intensity of mineralization of forming callus in the area of the damage is observed and the formation of bone regeneration slows down. Prospects for the use of nanocomposites of elemental selenium for modulation of reparative response are marked. The dynamics of the level of free circulating mitochondrial DNA (mtDNA) of blood in the early stages of experimental dyslipidemia has been studied. Atherogenic blood factors do not have a significant effect on the release of the mtDNA from dyslipidemia target cells. On the model of acute small-focal myocardial ischemia, we revealed the increase in the mtDNA levels. Prospects of broadcast of diagnostic mtDNA monitoring technology in myocardial ischemia have been marked. The mtDNA monitoring was first tested as a molecular risk pattern in acute coronary syndrome. In survived patients, the concentration of freely circulating mtDNA in blood plasma was 164 times lower. The probability of death of the patient with a high level of mtDNA (over 4000 copies/mL) was 50 % (logit analysis). Methodological level of translational research in the ISC SB RAS has increased due to effective participation in international multi-center clinical trials of drugs, mainly direct anticoagulants: fondaparinux, edoksabana, betriksabana. “Feedback broadcast” of the results of clinical trials of p38-kinase inhibitor, was carried out in the process of changing the model (initially – neuropathic pain) for coronary atherosclerosis. Technologies of pharmacogenetic testing and personalized treatment of diseases in the employees of the Irkutsk Scientific Center were applied. Step T2. Previously developed at the Irkutsk State Medical University and the Irkutsk Scientific Center of Surgery and Traumatologies approaches to surgical prevention and medicinal correction of postoperative hyposplenism were translated into practical health care. Thus, these results obtained in different areas of translational medicine will determine scientific topics of the department in future research cycle.

In Amyotrophic Lateral Sclerosis (ALS), neurons controlling voluntary muscles die, resulting in muscle weakness. Small animal studies have shown that neurons experience some regeneration when stem cells are injected into the ventral horn of the spinal cord [1]. These results led to large animal and human trials investigating the effects of injecting stem cells into the spinal cord. Direct injection is used for delivering cells as cells do not have to migrate to the therapy site and visual confirmation is possible [2]. This requires a multi-level laminectomy as well as dissection of the dura mater to expose the cell delivery site. In order to adopt this ALS treatment in regular clinical workflow, a minimally invasive alternative for spinal cord cell therapy is desirable. Image-guided needle targeting and positioning systems have been developed by numerous groups which use computed tomography or ultrasound for image guidance. However, MRI must be used for this ALS study because it is the only imaging system capable of visualizing the necessary anatomical locations for delivering cellular therapeutics to the spinal cord; the cell therapy target is the gray matter within the ventral horn of the spinal cord, and only MRI can detect the contrast between gray and white matter. Innomotion and NeuroArm have been used for MRI-guided interventions [3, 4] but they are complex, take a long time to set up, and take up a great deal of space in the MRI bore. An initial solution by our research group provided targeting solutions using an adjustable template on the spine, but was manually adjusted, targeted solely on a grid, and lacked a second rotation axis[5]. The presented device, SpinoBot, percutaneously directs therapeutics under MRI guidance into the spinal cord, allowing accurate and minimally invasive spinal therapies. This study examines the accuracy and workflow of MRI-guided cellular therapeutics injections using SpinoBot, a targeting and injection needle guidance system.

Background An estimated 292 million people are living with chronic hepatitis B virus (HBV) infection globally, including 223,000 people in Australia. HBV diagnosis and linkage of people living with HBV to clinical care is suboptimal in Australia, with 27% of people living with HBV undiagnosed and 77% not receiving regular HBV clinical care. This systematic review aimed to characterize population-level interventions implemented to enhance all components of HBV care cascade and analyse the effectiveness of interventions. Review questions Question 1: What population-level interventions, programs or policy approaches have been shown to be effective in reducing the incidence of hepatitis B; and that may not yet be fully rolled out or evaluated in Australia demonstrate early effectiveness, or promise, in reducing the incidence of hepatitis B? Question 2: What population-level interventions and/or programs are effective at reducing disease burden for people in the community with hepatitis B? Methods Four bibliographic databases and 21 grey literature sources were searched. Studies were eligible for inclusion if the study population included people with or at risk of chronic HBV, and the study conducted a population-level interventions to decrease HBV incidence or disease burden or to enhance any components of HBV care cascade (i.e., diagnosis, linkage to care, treatment initiation, adherence to clinical care), or HBV vaccination coverage. Studies published in the past 10 years (since January 2012), with or without comparison groups were eligible for inclusion. Studies conducting an HBV screening intervention were eligible if they reported proportion of people participating in screening, proportion of newly diagnosed HBV (participant was unaware of their HBV status), proportion of people received HBV vaccination following screening, or proportion of participants diagnosed with chronic HBV infection who were linked to HBV clinical care. Studies were excluded if study population was less than 20 participants, intervention included a pharmaceutical intervention or a hospital-based intervention, or study was implemented in limited clinical services. The records were initially screened by title and abstract. The full texts of potentially eligible records were reviewed, and eligible studies were selected for inclusion. For each study included in analysis, the study outcome and corresponding 95% confidence intervals (95%CIs) were calculated. For studies including a comparison group, odds ratio (OR) and corresponding 95%CIs were calculated. Random effect meta-analysis models were used to calculate the pooled study outcome estimates. Stratified analyses were conducted by study setting, study population, and intervention-specific characteristics. Key findings A total of 61 studies were included in the analysis. A large majority of studies (study n=48, 79%) included single-arm studies with no concurrent control, with seven (12%) randomised controlled trials, and six (10%) non-randomised controlled studies. A total of 109 interventions were evaluated in 61 included studies. On-site or outreach HBV screening and linkage to HBV clinical care coordination were the most frequent interventions, conducted in 27 and 26 studies, respectively. Question 1 We found no studies reporting HBV incidence as the study outcome. One study conducted in remote area demonstrated that an intervention including education of pregnant women and training village health volunteers enhanced coverage of HBV birth dose vaccination (93% post-intervention, vs. 81% pre-intervention), but no data of HBV incidence among infants were reported. Question 2 Study outcomes most relevant to the HBV burden for people in the community with HBV included, HBV diagnosis, linkage to HBV care, and HBV vaccination coverage. Among randomised controlled trials aimed at enhancing HBV screening, a meta-analysis was conducted including three studies which implemented an intervention including community face-to-face education focused on HBV and/or liver cancer among migrants from high HBV prevalence areas. This analysis demonstrated a significantly higher HBV testing uptake in intervention groups with the likelihood of HBV testing 3.6 times higher among those participating in education programs compared to the control groups (OR: 3.62, 95% CI 2.72, 4.88). In another analysis, including 25 studies evaluating an intervention to enhance HBV screening, a pooled estimate of 66% of participants received HBV testing following the study intervention (95%CI: 58-75%), with high heterogeneity across studies (range: 17-98%; I-square: 99.9%). A stratified analysis by HBV screening strategy demonstrated that in the studies providing participants with on-site HBV testing, the proportion receiving HBV testing (80%, 95%CI: 72-87%) was significantly higher compared to the studies referring participants to an external site for HBV testing (54%, 95%CI: 37-71%). In the studies implementing an intervention to enhance linkage of people diagnosed with HBV infection to clinical care, the interventions included different components and varied across studies. The most common component was post-test counselling followed by assistance with scheduling clinical appointments, conducted in 52% and 38% of the studies, respectively. In meta-analysis, a pooled estimate of 73% of people with HBV infection were linked to HBV clinical care (95%CI: 64-81%), with high heterogeneity across studies (range: 28-100%; I-square: 99.2%). A stratified analysis by study population demonstrated that in the studies among general population in high prevalence countries, 94% of people (95%CI: 88-100%) who received the study intervention were linked to care, significantly higher than 72% (95%CI: 61-83%) in studies among migrants from high prevalence area living in a country with low prevalence. In 19 studies, HBV vaccination uptake was assessed after an intervention, among which one study assessed birth dose vaccination among infants, one study assessed vaccination in elementary school children and 17 studies assessed vaccination in adults. Among studies assessing adult vaccination, a pooled estimate of 38% (95%CI: 21-56%) of people initiated vaccination, with high heterogeneity across studies (range: 0.5-93%; I square: 99.9%). A stratified analysis by HBV vaccination strategy demonstrated that in the studies providing on-site vaccination, the uptake was 78% (95%CI: 62-94%), significantly higher compared to 27% (95%CI: 13-42%) in studies referring participants to an external site for vaccination. Conclusion This systematic review identified a wide variety of interventions, mostly multi-component interventions, to enhance HBV screening, linkage to HBV clinical care, and HBV vaccination coverage. High heterogeneity was observed in effectiveness of interventions in all three domains of screening, linkage to care, and vaccination. Strategies identified to boost the effectiveness of interventions included providing on-site HBV testing and vaccination (versus referral for testing and vaccination) and including community education focussed on HBV or liver cancer in an HBV screening program. Further studies are needed to evaluate the effectiveness of more novel interventions (e.g., point of care testing) and interventions specifically including Indigenous populations, people who inject drugs, men who have sex with men, and people incarcerated.