Clinical Trial Funding Research Articles

Patient and public involvement in the design of an international clinical trial: real world experience

BackgroundThe value of patient and public involvement (PPI) during the earliest stages of clinical trial development, and prior to the award of substantive funding, is widely recognised. However, it is often under-resourced and PPI processes during this phase are rarely reported in detail. Having benefitted from seed funding to develop an international clinical trial proposal, we sought to describe and appraise PPI activities and processes that support pre-award co-development.MethodsA 12-month “accelerator” award facilitated development of a substantive funding application to deliver the Rheumatoid Arthritis Prevention PlatfORm Trial (RAPPORT), conceived to prioritise preventative interventions for people at risk of RA. PPI partners, including individuals at risk of rheumatoid arthritis (RA), RA patients, relatives and members of the public, provided feedback on key trial design issues through online meetings, a feedback form and emails. PPI processes employed during the one-year accelerator project were thereafter evaluated by PPI partners using an anonymous online feedback form with reference to National Institute of Health and Care Research (NIHR) UK standards for public involvement in research.ResultsSixteen out of the 25-strong PPI partner panel completed an online feedback form (64%). Respondents perceived PPI processes positively in relation to all NIHR standard domains. Several key facilitators and challenges were identified, including the need for adequate PPI funding during pre-award phases of research, strategies for creating an inclusive environment, flexibility around levels of involvement, and challenges in achieving representatively diverse participation, and the importance of communicating transparent processes for role-assignment and time-reimbursement.ConclusionsIn general, RAPPORT was considered an example of PPI well done, and in line with UK standards for public involvement in research. Facilitators and challenges of relevance for the development of future translational and clinical trial funding applications are highlighted.

Research prioritization in hernia surgery: a modified Delphi ACHQC and VHOC expert consensus

PurposeNumerous clinical practice guidelines and consensus statements have been published in hernia surgery, however, there is still a need for high-quality evidence to address remaining unanswered questions. The aim of this study was to conduct research priority setting through a modified Delphi process to identify a list of top research priorities in hernia surgery.MethodsA structured literature review of clinical practice guidelines was performed by the steering committee. Topics considered clinically significant, practical to study and lacking strong evidence were extracted and refined into a comprehensive list, then entered into a two-round Delphi survey for prioritization at the Abdominal Core Health Quality Collaborative (ACHQC) Quality Improvement Summit. In round 1, participants were instructed to select any topic that should be prioritized for future research. Topics were ranked according to the proportion of votes and the 25 highest-ranking topics were included in the second round. In round 2, participants were instructed to select only the top 10 topics for research prioritization.ResultsEleven clinical practice guidelines were reviewed. Eighty-seven topics were extracted by the steering committee and submitted for prioritization. After the first round, 25 of the highest-ranking topics were determined and included in the second round. A final list of 11 research questions was identified. The hernia types with the most research interest were inguinal and epigastric/umbilical hernias. Other topics of high interest were the management of diastasis recti, primary versus mesh repairs and expectant management versus surgical repair.ConclusionOur study provides a research agenda generated through expert consensus that may be used in the prioritization of the design and funding of clinical trials in hernia surgery.

Experience of Health professionals in the implementation of Clinical trials of Traditional Herbal Medicines: A cross-sectional study in Mali

Objective: The objective of this study was to determine the experience of health professionals in clinical trials of traditional herbal medicines in Mali. Material and methods: This was a cross-sectional study conducted from June to December 2022 among healthcare professionals in three randomly selected localities: the district of Bamako and the regions of Koulikoro and Sikasso. Data were collected by direct interview using an anonymous questionnaire. The Chi-square (χ2) test was used to assess factors associated with participation in clinical trials of traditional medicines. Results: The involvement of healthcare professionals in clinical trials of traditional medicines was low (3.5%) and was associated with age (p=0.021). The obstacles to conducting these trials reported by healthcare professionals were lack of funding and failure to take account of the specificities of traditional medicines in clinical trial regulations. Some healthcare professionals suggest ethnomedical evaluation of recipes proposed by traditional practitioners and the use of reverse pharmacology as alternatives. Conclusion: Research into traditional medicines could be given greater impetus by the long-term funding of clinical trials and by less costly alternatives such as the ethnomedical evaluation of recipes proposed by traditional healers and reverse pharmacology.

Impact of industry funding on atrial fibrillation clinical trials: insights and implications

Abstract Background/Introduction Commercial industry is an important source of funding for atrial fibrillation clinical trials, the implications of which have not been analyzed. Purpose The purpose of this study is to describe the characteristics of contemporary AF clinical trials and to evaluate their association with funding source. Methods We systematically assessed all completed atrial fibrillation trials registered in ClinicalTrials.gov between conception to September 1, 2022, and extracted publicly available information including funding source, trial size, race, ethnicity, sex, intervention, location, and publication status. Trial characteristics were compared using the Wilcoxon rank sum test and Fisher’s exact test for continuous and categorical variables, respectively. Results Of the 253 clinical trials assessed, 171 (68%) reported industry funding. Industry funding was associated with a greater median total enrollment (172 vs. 80; P < 0.001), publication rate (56.7% vs. 42.7%; P = 0.04), participation in device trials (48.0% vs. 24.4%; P < 0.001), and multicontinental recruitment location (25.2% vs. 2.4%; P < 0.001) when compared to non-industry funded clinical trials. However, industry funding was not associated with a significant difference in median impact factor (7.7 vs. 7.7; P = 0.723) or median number of citations (60.0 vs. 29.0; P = 0.09). The overall proportion of industry funded trials did not change over time (P = 1.00) since inception of the ClinicalTrials.gov database. Participant demographics remained relatively uniform over time across both industry-funded and non-industry-funded trials. Conclusion(s). Industry funded clinical trials in atrial fibrillation are often larger, more frequently published, multicontinental, and device-focused. Industry funding was found to be associated with significant differences in study enrollment, publication metrics, and study interventions. Insights from this study inform trial design, regulation, and policy considerations in the evolving landscape of AF research.TableFigure

Abstract PO2-11-09: European Lobular Breast Cancer Advocates: Bridging the Geographical Gaps in Lobular Breast Cancer Education and Awareness

Abstract Introduction In 2019, Invasive Lobular Cancer (ILC) Patient Advocates attended the 3rd meeting of the European Lobular Breast Cancer Consortium (ELBCC), a scientific community focused on lobular research and treatment. European Lobular Breast Cancer Advocates (ELBCA) now have a network of ILC patient advocates across Europe. ILC is classified by the World Health Organisation as the most common Special Type of Breast Cancer. In 2022 there were 576,300 diagnoses of breast cancer in Europe, 15% ~86,500 were ILC. ILC is a histologically distinct breast cancer with diverse presentations including a tendency to metastasize to unique locations. Current endocrine therapies may have different effectiveness for ILC making treatment challenging. Current imaging tools are often unreliable with up to 30% of ILC tumours not identified on mammograms and detection is often delayed. Challenges There are no standardised European diagnostic or treatment protocols for ILC. ELBCA addresses this with collaborative efforts between ILC medical professionals and researchers. It’s a major challenge because each European country has a different health care system and economic policy structure. It’s also a challenge to streamline the translation of clinically accurate information to European patients in their own language. Not all European countries are members of the EU, there are a minimum of 24 official European languages. Established European breast cancer patient organizations often don’t distinguish between different histological subtypes. Current European policy and administrative processes have hindered the formation of a not-for-profit Advocacy Organization. Without such an organization, fundraising and collaborative efforts with others is difficult. Conclusions ELBCA has made significant progress towards raising awareness and increasing knowledge of ILC across Europe. Our poster will expand on these accomplishments as well as the following goals: Work with European and International ILC research and patient communities to better understand this unique histological subtype. Elevate ILC research priorities and inform European policy to recognize ILC as a distinct disease. Enhance education of ILC among primary HCP’s and patients. Establish a recognized European ILC Advocacy Organization and collaborate with established BC organizations. Attend major BC research and clinical conferences. Lobby to achieve increased funding for ILC research and clinical trials. Citation Format: Siobhan Freeney, Helene Bonval, Esther Geven, Lori Petitti, Rian Terveer, Claire Turner, Cathrin Brisken, Patrick Derksen, Christine Desmedt, Thijs Koorman, ADRIAN LEE, Steffi Oesterreich, Anne Salomon, George Sflomos, Karen Van Baelen, Tone Lien, Damir Vareslija, Sabine Linn. European Lobular Breast Cancer Advocates: Bridging the Geographical Gaps in Lobular Breast Cancer Education and Awareness [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-11-09.

Using healthcare systems data for outcomes in clinical trials: issues to consider at the design stage

BackgroundHealthcare system data (HSD) are increasingly used in clinical trials, augmenting or replacing traditional methods of collecting outcome data. This study, PRIMORANT, set out to identify, in the UK context, issues to be considered before the decision to use HSD for outcome data in a clinical trial is finalised, a methodological question prioritised by the clinical trials community.MethodsThe PRIMORANT study had three phases. First, an initial workshop was held to scope the issues faced by trialists when considering whether to use HSDs for trial outcomes. Second, a consultation exercise was undertaken with clinical trials unit (CTU) staff, trialists, methodologists, clinicians, funding panels and data providers. Third, a final discussion workshop was held, at which the results of the consultation were fed back, case studies presented, and issues considered in small breakout groups.ResultsKey topics included in the consultation process were the validity of outcome data, timeliness of data capture, internal pilots, data-sharing, practical issues, and decision-making. A majority of consultation respondents (n = 78, 95%) considered the development of guidance for trialists to be feasible. Guidance was developed following the discussion workshop, for the five broad areas of terminology, feasibility, internal pilots, onward data sharing, and data archiving.ConclusionsWe provide guidance to inform decisions about whether or not to use HSDs for outcomes, and if so, to assist trialists in working with registries and other HSD providers to improve the design and delivery of trials.

Clinical trials landscape in a lower-middle-income country (Pakistan).

In recent times, there have been calls from within the developing nations for increased ownership by governmental research bodies and universities of the priority research setting and research that aligns with national health strategies. This is a review paper of the studies that have been published on clinical trials in developing countries, with a focus mainly on Pakistan. The literature review used online databases such as PubMed, Scopus, and Google Scholar, World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov trial registries to search for clinical trials conducted in Pakistan between January 2000 and December 2022 and analyzed. The results revealed that clinical research in Pakistan is hindered by a number of barriers, including a lack of funding, skilled personnel, and regulatory issues. Lack of funding is a common obstacle, and the majority of funding for clinical trials originates from Western countries or pharmaceutical companies established in the West. In conclusion, clinical studies in developing countries, especially in Pakistan, are hindered by a plethora of barriers, and to improve the current state, increasing funding, streamlining ethical approval procedures, simplifying regulatory systems, addressing cultural and religious concerns, and participating in global efforts to bridge the gap in health-based research are crucial.

Characteristics of Clinical Trials for Multiple Myeloma and CAR-T Cell Therapy: A Cross Sectional Analysis

Background: In recent decades novel CAR-T cell therapies have proven efficacious in the treatment of multiple myeloma, leading to FDA approval. As CAR-T cell therapies continue to be developed in clinical trials, it is important to assess trends over time that can inform drug development and relate to equitable access and representation. This cross-sectional study was conducted to analyze the characteristics of clinical studies for multiple myeloma and CAR-T cell therapy registered in ClinicalTrials.gov (CTG). Methods: All multiple myeloma clinical studies registered on CTG from September 27, 2007 to July 15, 2023 were identified using Advanced Search feature in ClinicalTrials.gov. Trial characteristics were assessed through relative frequency calculations. Odds ratio and 95% confidence intervals were determined for key characteristics and significance of findings. Results: Out of the 390,301 studies registered in CTG during this period, a mere 0.63% (2,457 studies) were conducted for multiple myeloma, compared to 1.61% (6,287 studies) for lymphoma and 1.46% (5,699 studies) for leukemia. Among these multiple myeloma studies, 85.47% (2,100 studies) were interventional and 14.82% (364 studies) were observational. Further, a total of 184 studies for CAR-T cell therapy in multiple myeloma were found in CTG registered during this period. Among these, 124 studies are still ongoing, constituting around 12.53% of the total 990 ongoing multiple myeloma studies. In multiple myeloma, around 51.98% (1276 studies) were industry sponsored, while 12.75% (313 studies) received funding from the National Institutes of Health (NIH) and other U.S. federal agencies (FA). The remaining 36.7% (901 studies) were funded by all others including individuals, universities and other research organizations. Similar funding trends were observed for 984 ongoing clinical studies. Notably, there were statistically significant differences in funding trends for CAR-T cell therapy within multiple myeloma studies. Industry funded a higher percentage for CAR-T cell therapy, 66.3%, compared to the overall 51.98% multiple myeloma studies that were industry sponsored. Further, NIH/ FA provided funding in 12.5% studies for CAR-T for CAR-T cell therapy, compared to a much lower 4.9% of all multiple myeloma studies. Interestingly, the premature discontinuation rates for CAR-T cell therapy clinical studies in multiple myeloma were significantly lower than those observed in overall multiple myeloma studies (OR 0.33; CI 0.177 to 0.611; p<0.01). This is promising for adherence in a heavily pretreated population. However, the proportion of studies with unknown status were significantly higher when compared to the overall multiple myeloma studies. (OR 2.84; 95% CI 1.94 to 4.18; p<0.01). There was no statistically significant difference between the unknown status and premature discontinuation rates of CAR-T cell therapy studies in multiple myeloma are myeloma compared to those in lymphoma. Conclusion: This cross-sectional study demonstrates that CAR T-cell therapy for multiple myeloma remains of prominent interest to industry followed by NIH and other U.S. funding organizations. There were significant trends noted that can inform drug development policy and relate to access and representation in trials. While the trends in the study discontinuation trends are promising, there is a need to address the proportion of studies with unknown status. Improved reporting and research into clinical trial funding and design will optimize efforts in developing cellular therapies for patients with myeloma.

Challenges and opportunities for continued access to effective antibiotics - what role for the EU?

Abstract Large pharmaceutical companies have withdrawn from antibiotic R&D because of the high risk of failure and because antibiotics are less profitable than other areas; small and medium-sized enterprises (SMEs), which now drive antibiotic R&D, face difficulty securing funding for preclinical and early clinical trials, and risk significant economic losses when launching new antibiotics. To reinvigorate the antibiotic pipeline, a holistic package of aligned incentives is required, which takes into account public health factors, improves return of investment while supporting SMEs, and considers operational feasibility including potential political, regulatory, legislative, industry and financial hurdles. This presentation will highlight the main options in this area. Improving access to effective antibiotics requires both short- and longer-term measures. Reducing regulatory administrative hurdles, engaging in good procurement practice, increasing joint purchasing efforts, and considering payment models that de-link revenue from sales can keep older (but effective) antibiotics on the market by ensuring their economic viability. Strengthening the mapping of production capacities and product availability can improve transparency and identify options for action, while stockpiling and strengthening manufacturing capacities within and outside of the EU can boost the supply chain itself. Concrete measures and their feasibility will be briefly presented. The EU has a major role to play by supporting antibiotic R&D and engaging with other international efforts to promote optimal deployment of incentives, by ensuring that the lack of access to appropriate and effective antibiotics is recognized as a threat to global health security, and by building on its relationships with international institutions to act as a facilitator in the global space towards ensuring synergies among existing structures, communicating the cost of inaction, and supporting national and regional initiatives. Speakers/Panelists Danilo Lo Fo Wong Division of Country Health Programmes, WHO/Europe, Copenhagen, Denmark Malin Grape Ministry of Health and Social Affairs, Stockholm, Sweden Lieven De Raedt Federal Public Service Health, Food Chain Safety and Environment, Brussels, Belgium

SAT656 Weight Reduction After 6 Months Of Setmelanotide Treatment In Patients With Hypothalamic Obesity

Abstract Disclosure: C.L. Roth: Other; Self; Received research support from Rhythm Pharmaceuticals, Inc. A.H. Shoemaker: Advisory Board Member; Self; Received payments from Rhythm Pharmaceuticals, Inc and Saniona for advisory boards and lectures. Other; Self; Received research support from Rhythm Pharmaceuticals, Inc. M. Gottschalk: Advisory Board Member; Self; Received compensation for consulting and participation on advisory boards from Rhythm Pharmaceuticals, Inc. Other; Self; Received funding for clinical trials from Rhythm Pharmaceuticals, Inc. J. Miller: Other; Self; Received research support from Harmony Biosciences, Rhythm Pharmaceuticals, Inc, Soleno Therapeutics, and Tryp Therapeutics. G. Yuan: Employee; Self; Employee of Rhythm Pharmaceuticals, Inc. Stock Owner; Self; Has company-awarded RSU and options. S. Malhotra: Employee; Self; Employee of Rhythm Pharmaceuticals, Inc. Stock Owner; Self; Stockholder in in Rhythm Pharmaceuticals, Inc. C. Scimia: Employee; Self; Employee of Rhythm Pharmaceuticals, Inc. Stock Owner; Self; Has company-awarded RSU and options. M. Abuzzahab: Advisory Board Member; Self; Received compensation for advisory board participation from Consynance, Endo Pharmaceutical, Pfizer, and Rhythm Pharmaceuticals, Inc. Consulting Fee; Self; Received compensation for consulting from Consynance, Endo Pharmaceutical, Pfizer, and Rhythm Pharmaceuticals, Inc. Speaker; Self; Received compensation for speaking engagements from Consynance, Endo Pharmaceutical, Pfizer, and Rhythm Pharmaceuticals, Inc. Other; Self; Received research support from Ascendis, Levo Pharmaceuticals, Lumos, NovoNordisk, Rhythm Pharmaceuticals, Inc, Saniona, and Soleno. Background: Hypothalamic obesity (HO) is an acquired form of severe obesity characterized by rapid and excessive weight gain resulting from insult to the hypothalamus—primarily caused by tumor invasion, resection, or radiotherapy—that can impair melanocortin-4 receptor (MC4R) pathway signaling. Treatment with setmelanotide, an MC4R agonist, resulted in weight loss and hunger reduction at 16 weeks in a Phase 2 trial of patients with HO. Here, we report changes in age-appropriate weight-related parameters after 6 months of treatment with setmelanotide in patients with HO who entered a long-term extension (LTE) trial. Methods: A Phase 2, multicenter, open-label study (NCT04725240) examined the efficacy and safety of 16-week setmelanotide treatment in patients aged ≥6 to ≤40 years with a clinical diagnosis of HO. Patients who met the primary endpoint of ≥5% body mass index (BMI) reduction from baseline at Week 16 or experienced investigator-determined clinically meaningful benefit and demonstrated adequate safety were eligible to enroll in the LTE trial (NCT03651765). We assessed the proportion of patients who achieved ≥10% BMI reduction as well as changes in age-appropriate weight-related parameters (ie, mean percent change in body weight for adults [aged ≥18 years] and mean change in BMI Z score and percent of the 95th BMI percentile [%BMI95] for children [aged <18 years]) from index trial baseline to Month 6 of setmelanotide treatment. Results: Of 18 patients originally enrolled in the index trial, 14 (77.8%) continued into the LTE and 13 (72.2%) had received ≥6 months of setmelanotide treatment at the time of this analysis. HO was diagnosed in these patients secondary to treatment of craniopharyngioma (n=11), hypothalamic hamartoma (n=1), and juvenile pilocytic astrocytoma (n=1). At Month 6, 11 of 13 patients (84.6% [90% confidence interval, 59.0%–97.2%) achieved ≥10% BMI reduction from index trial baseline; the remaining 2 patients achieved ≥5% reduction from baseline at Month 6. In adults (n=2), the mean (standard deviation [SD]) percent change in body weight from baseline to Month 6 was −16.2% (7.2%). In children (n=11), the mean (SD) change from baseline in BMI Z score was −1.7 (1.1) and in %BMI95 was −34.8 (14.9) percentage points at Month 6. The most frequent adverse events were nausea (n=9 [69.2%]), skin hyperpigmentation (n=5 [38.5%]), and vomiting (n=4 [30.8%]). Four serious adverse events were reported in 2 patients (Clostridium difficile colitis in 1 patient; malaise, septic shock, and influenza in 1 patient) and were determined not related or unlikely related to study drug. Conclusions: In a heterogeneous population of patients with HO secondary to treatment of hypothalamic tumors, 6 months of setmelanotide treatment was associated with sustained meaningful improvements in weight and BMI with no new safety signals. Presentation: Saturday, June 17, 2023

Characterizing Clinical Trials in Plastic and Reconstructive Surgery: A Systematic Review of ClinicalTrials.gov From 2007 to 2020.

Clinical trials form the backbone of evidence-based medicine. ClinicalTrials.gov is the world's largest clinical trial registry, and the state of clinical trials in plastic and reconstructive surgery (PRS) within that database has not been comprehensively studied. To that end, we explored the distribution of therapeutic areas that are under investigation, impact of funding on study design and data reporting, and trends in research patterns of all PRS interventional clinical trials registered with ClinicalTrials.gov. Using the ClinicalTrials.gov database, we identified and extracted all clinical trials relevant to PRS that were submitted between 2007 and 2020. Studies were classified based on anatomic locations, therapeutic categories, and specialty topics. Cox proportional hazard was used to calculate adjusted hazard ratios (HRs) for early discontinuation and results reporting. A total of 3224 trials that included 372,095 participants were identified. The PRS trials grew at an annual rate of 7.9%. The therapeutic classes most represented were wound healing (41.3%) and cosmetics (18.1%). Funding for PRS clinical trials is largely provided through academic institutions (72.7%), while industry and US government constituted a minority. Industry-funded studies were more likely to be discontinued early than those funded by academics (HR, 1.89) or government (HR, 1.92) and to be nonblinded and nonrandomized. Academic-funded studies were the least likely to report results data within 3 years of trial completion (odds ratio, 0.87). A gulf exists in the representation of different PRS specialties among clinical trials. We highlight the role of funding source in trial design and data reporting to identify a potential source of financial waste and to stress the need for continued appropriate oversight.

The effect of the COVID-19 pandemic on US Food and Drug Administration-funded clinical trials and natural history studies for rare diseases

BackgroundSince 1983, the Orphan Product Grants Program, administered by the US Food and Drug Administration, provides funding for clinical trials and natural history studies in rare diseases. The COVID-19 pandemic created new challenges in rare disease product development. This study sought to determine the effects of the pandemic on rare disease studies using data from grantees of this program, and determine lessons learned that can potentially be applied to future trials in rare diseases. MethodsAll grants that were being funded by the Orphan Products Grants Program between March 2020 and March 2021 were included in the study. Data was gathered from grantees and described the effects of the pandemic on multiple aspects of the studies including enrollment, patient follow-up, protocol, and budget. ResultsThere were 62 grants active during the study period, and of these 54 (87%) were clinical trials and 8 (13%) were natural history studies. 94% of the grantees reported their studies being affected by the COVID-19 pandemic, and the addition of virtual capabilities was reported by 34 (55%) of grantees. ConclusionsThis study suggested two important lessons learned. First, virtual capabilities, when appropriate, can be an important component of trials because they decrease the travel burden on participants and reduce in-person risks, which should increase patient recruitment and retention. Second, building in flexibility in clinical trials is critical in the post-COVID era and could include increasing the use of multi-site trials, clinical networks, and innovative designs and collaborations to speed up trials without compromising study data.

A call to address structural barriers to Hispanic/Latino representation in clinical trials on Alzheimer's disease and related dementias: A micro-meso-macro perspective.

This perspective paper addresses the US Hispanic/Latino (herein, Latino) experience with regards to a significant public health concern-the underrepresentation of Latino persons in Alzheimer's disease and related dementias (AD/ADRD) clinical trials. Latino individuals are at increased risk for AD/ADRD, experience higher disease burden, and low receipt of care and services. We present a novel theoretical framework-the Micro-Meso-Macro Framework for Diversifying AD/ADRD Trial Recruitment-which considers multi-level barriers and their impact on Latino trial recruitment. Based on a review of the peer-reviewed literature and our lived experience with the Latino community, we drew from our interdisciplinary expertise in health equity and disparities research, Latino studies, social work, nursing, political economy, medicine, public health, and clinical AD/ADRD trials. We discuss factors likely to impede or accelerate Latino representation, and end with a call for action and recommendations for a bold path forward. In the 200+ clinical trials conducted with over 70,000 US Americans, Latino participants comprise a fraction of AD/ADRD trial samples. Efforts to recruit Latino participants typically address individual- and family-level factors (micro-level) such as language, cultural beliefs, knowledge of aging and memory loss, limited awareness of research, and logistical considerations. Scientific efforts to understand recruitment barriers largely remain at this level, resulting in diminished attention to upstream institutional- and policy-level barriers, where decisions around scientific policies and funding allocations are ultimately made. These structural barriers are comprised of inadequacies or misalignments in trial budgets, study protocols, workforce competencies, healthcare-related barriers, criteria for reviewing and approving clinical trial funding, criteria for disseminating findings, etiological focus and social determinants of health, among others. Future scientific work should apply and test the Micro-Meso-Macro Framework for Diversifying AD/ADRD Trial Recruitment to examine structural recruitment barriers for historically underrepresented groups in AD/ADRD research and care.

Biofeedback Has Therapeutic Effects on Asthma, Although Additional Research Is Needed to Document Specificity

Asthma is a common disorder leading to significant disability and healthcare cost throughout the world. Although medical treatment is usually highly effective in controlling it, asthma medicines often have high costs and attendant side effects. Biofeedback is an inexpensive noninvasive alternative with minimal side effects. This paper reviews evidence for two validated biofeedback treatments for treating asthma, heart rate variability biofeedback (HRVB), and muscle relaxation with surface electromyographic biofeedback. In multiple studies, although most of them are of modest size, both methods have clinically meaningful results, often allowing decreases in the use of steroid medication. Further research is needed to prove which specific components of HRVB are responsible for clinical effects, and to determine asthma populations that can best benefit from these methods. Despite demonstrated effectiveness, few insurance schemes reimburse for biofeedback, and national guidelines consider it only as worthy of further investigation. Funding for the requisite large-scale clinical trials remains lacking, creating a limbo-like status quo for these useful methods.

Seventy Years of Antipsychotic Development: A Critical Review.

Since the mid-1950s discovery of the first effective antipsychotic medications (APM), we have only been able to improve the tolerability but not the overall efficacy of currently available APMs, as reflected by effectiveness trials in Europe and the United States. This inability to develop more effective APMs is attributable to multiple factors, including failure to create and use assessment tools to assess core symptom domains in schizophrenia, move beyond the dopaminergic hypothesis and to develop "me too" drugs, imposing ill-defined research domain criteria, and lacking federal funding for clinical trials. The classification of APMs is also confusing, including second-generation, partial agonists, and multimodal APMs in the same class of APMs, despite significant differences in their mechanisms of action. Other factors stagnating drug development include inadequate sample sizes to address heterogeneity, lack of statistical measures correlating with clinical significance, using the atheoretical basis of psychiatric diagnoses, failure to control placebo response, and high cost of newer and perhaps more tolerable APMs. Furthermore, there has been a failure to develop early predictors of antipsychotic response and various tools to optimize an APM response. Finally, some mental health providers are also responsible for the suboptimal use of APMs, by using excessive maintenance doses, often with irrational polypharmacy, further compromising effectiveness and medication adherence. However, some bright spots in antipsychotic development include improved tolerability of APMs and long-acting injectables to address the high prevalence of medication nonadherence. This review critically reviews 70 years of antipsychotic development, the reasons behind the failure to develop more effective APMs, and suggestions for future direction.

A 15 Year Evolution of Dichloroacetate-Based Metabolic Cancer Therapy: A Review with Case Reports

Despite Otto Warburg’s discovery of aerobic glycolysis in cancer cells in the 1920’s, the potential for developing therapeutics that targeted cancer cell metabolism was essentially ignored until 2007 when a groundbreaking publication was released from a group of Canadian researchers. Bonnet et al. (who paradoxically were not specialized in oncology) discovered that the generic drug dichloroacetate sodium (“DCA”) could reverse the Warburg phenotype in cancer cells in vitro and in vivo resulting in natural cancer cell suicide and tumour shrinkage in rats. This phenomenon was previously thought to be impossible as it was believed that mitochondria in malignant cells were permanently altered and unable to trigger apoptosis. Despite the fact that no large clinical trial of DCA as a cancer therapy was ever completed, a small number of doctors in North America and Europe rapidly translated this new knowledge into clinical cancer protocols through independent observational research and creative thinking. Since off-label drug use is permitted in most jurisdictions, clinicians initially began to use DCA in patients who had failed all conventional therapies. Over the years, further novel anti-cancer mechanisms of DCA were discovered such as angiogenesis inhibition, immune activation and cancer stem cell targeting. Around 2011, the work of Seyfried (USA) began to illuminate the importance of glutamine inhibition and suggested that a multi-energetic targeted approach was superior to glycolysis inhibition alone. A collaborative effort of the authors incorporating Seyfried’s concepts resulted in the creation of a new metabolic protocol named “MOMENTUM” (Metabolic, Oncologic, Multi-ENergetic Targeted, Universal, Modified). In this protocol, glucose and glutamine metabolism were targeted simultaneously with a combination of multiple natural and pharmacologic agents administered intravenously. Surprising preliminary clinical results in several difficult cancer cases confirmed that metabolic multi-targeted methods are extremely promising, and more so than metabolic monotherapy. Life threatening side effects of this approach to cancer management are virtually non-existent and therapy costs are manageable. A disappointing absence of industry funding for large clinical trials has not curtailed the development of the metabolic approach as a clinically viable methodology, proving that unadulterated medical science can conquer the ongoing push for multibillion-dollar economic reward.

OP57 The Identification Of Technological Innovations To Address The Challenge Of Antimicrobial Resistance Using Horizon Scanning Approaches

IntroductionInappropriate prescribing of antibiotics is a significant driver of antimicrobial resistance (AMR) which is a global health challenge. Technological innovations present an opportunity to reduce demand for antimicrobials through infection prevention, detection, and management. The National Institute for Health and Care Research (NIHR) Innovation Observatory (IO) has developed horizon scanning methods to identify promising innovations (devices/diagnostics/digital) and anticipate technological trends. Together these insights build a comprehensive landscape and presents a significant opportunity for decision-makers and HTAs to consider the clinical, financial, infrastructural, and logistical provisions to improve preparedness for the potential adoption of these future innovations.MethodsThe IO developed a detailed dataset of technologies by formulating search strategies for AMR, based on a comprehensive list of terms and input from expert panels. Primary and secondary sources were systematically scanned using a combination of traditional scanning methods, automated and novel artificial intelligence (AI)/machine learning techniques. Sources included clinical trial registries, MedTech news, academic sources, funding agencies, commercial sites, and regulatory authorities.ResultsOur global dataset identified over 3000 innovative preventative, detection, and monitoring technologies mapped across AMR clinical pathways (including sepsis, respiratory tract infections). Development activity largely concentrated in the United States of America and United Kingdom. Emerging trends included the application of novel materials to prevent infections (e.g., catheter coatings) and novel analytical techniques (e.g., biosensors, microfluidics, breath analysis) to support optimal patient treatment. Data analysis revealed a high proportion of technologies were diagnostic innovations addressing unmet needs such as rapid and accurate detection (including drug-resistant infections).ConclusionsThe rapid development and application of technological interventions presents an opportunity to strengthen national AMR strategies worldwide, through the adoption of new innovations. Improvements in exiting technologies, along with technological advancements have the potential to support appropriate prescribing of antimicrobials and thus address the rise in AMR.

Forty years of investment in HIV research: progress towards ending the HIV pandemic and preparation for future pandemics.

Forty years of investment in HIV research: progress towards ending the HIV pandemic and preparation for future pandemics.

Effect of dupilumab on Eustachian tube dysfunction in patients with chronic rhinosinusitis with nasal polyposis.

Peter H. Hwang: Speaker Bureau for Sanofi, Speakers Bureau and clinical trial funding for GlaxoSmithKline. All other authors declare no conflicts of interest.

Itch-free state in patients with atopic dermatitis treated with ruxolitinib cream: A pooled analysis from two randomized phase 3 studies

Itch-free state in patients with atopic dermatitis treated with ruxolitinib cream: A pooled analysis from two randomized phase 3 studies