Clinical Research Studies Research Articles

Medical Writing Bias in Myeloma Clinical Research: A Comprehensive Analysis

Background Previous studies investigating associations between pharmaceutical funding and clinical trial results have found ties between pharmaceutical sponsorship and results favoring the sponsor's interests. There are no studies examining potential sponsorship bias within the field of multiple myeloma (MM). Addressing sponsorship bias is essential to ensure reliability, validity, and ethical conduct of clinical research in the field of MM. This study analyzes potential sponsorship bias in MM specifically regarding use of medical writers that are employees of or directly funded by pharmaceutical companies among published clinical research studies of drugs approved to treat MM from January 2000 - March 2023. Methods Clinical study papers from PubMed between January 2000 and March 2023 were analyzed if at least 1 of the 10 following drugs were evaluated: bortezomib (BORT), carfilzomib (CARF), daratumumab (DARA, elotuzumab (ELO), isatuximab (ISA), ixazomib (IXA), lenalidomide (LEN), panobinostat (PAN), pomalidomide (POM), and selinexor (SELI), and the manufacturer of the drug(s) sponsored the study (N=1466). Papers were considered to contain potential medical writing bias if the paper was written by employees of the manufacturer of the drug(s) or medical writers directly funded by the manufacturer. Papers were analyzed by year, drug, and journal in which it was published. Results From 2000 - March 2006, no potential writing bias occurred. In 2007, it first became apparent when 4% (2/53) of papers showed bias which has increased as follows: 2008 - 2012 [14% (41/300)], 2013 - 2017 [25% (100/405)], 2018-2022 [33% (171/521)], and increased to 44% (12/27) in 2023. We also analyzed writing bias according to the specific drugs from January 2000 - March 2023 with the following rates of potential bias: ISA 93% (26/28), IXA 77% (36/47), DARA 76% (63/83), ELO 71% (17/24), SELI 62% (8/13), POM 55% (27/49), PAN 50% (9/18), BORT 47% (47/100), LEN 46% (75/163) and CARF 32% (15/47). Potential writing bias was also determined according to the specific medical journal in which the paper was published from 2000 - March 2023. Blood and British Journal of Haematology have the highest number of potentially biased manuscripts at 42 and 30, respectively, representing 25% (42/142) and 21% (30/143) of the papers published, respectively. New England Journal of Medicine and Lancet have high percentages of potential writing bias at 33% (9/27) and 46% (6/13), respectively. Many journals have 100% (n=6) but these sources only had 1 paper meeting the study criteria. Conclusion Since 2000, we have observed an alarming increase in the rate of clinical research papers evaluating drugs approved to treat MM which have been written by pharmaceutical company employees or medical writers directly funded by them. Notably, nearly half (44%) of papers published this year showed potential writing bias. Rates varied greatly between different drugs with ISA, IXA and DARA showing the highest rates of writing bias whereas BORT, LEN and CARF showed the lowest rates. Specific journals including Blood and British Journal of Haematology both show high numbers of papers with potential writing bias; and, furthermore, a high percentage of papers published in high impact journals such as the New England Journal of Medicine and Lancet show this type of potential bias. This practice of allowing medical writing to be carried out by those with direct ties to the pharmaceutical company is likely to result in the publication of papers with results and conclusions regarding the efficacy and safety of drugs that are biased which compromises their scientific integrity and objectivity.

Navigating the Complexities of Traumatic Encephalopathy Syndrome (TES): Current State and Future Challenges.

Chronic traumatic encephalopathy (CTE) is a unique neurodegenerative disease that is associated with repetitive head impacts (RHI) in both civilian and military settings. In 2014, the research criteria for the clinical manifestation of CTE, traumatic encephalopathy syndrome (TES), were proposed to improve the clinical identification and understanding of the complex neuropathological phenomena underlying CTE. This review provides a comprehensive overview of the current understanding of the neuropathological and clinical features of CTE, proposed biomarkers of traumatic brain injury (TBI) in both research and clinical settings, and a range of treatments based on previous preclinical and clinical research studies. Due to the heterogeneity of TBI, there is no universally agreed-upon serum, CSF, or neuroimaging marker for its diagnosis. However, as our understanding of this complex disease continues to evolve, it is likely that there will be more robust, early diagnostic methods and effective clinical treatments. This is especially important given the increasing evidence of a correlation between TBI and neurodegenerative conditions, such as Alzheimer's disease and CTE. As public awareness of these conditions grows, it is imperative to prioritize both basic and clinical research, as well as the implementation of necessary safe and preventative measures.

Data-Driven Precision Nutrition Improves Clinical Outcomes and Risk Scores for IBS, Depression, Anxiety, and T2D

Many studies have shown that foods and nutritional ingredients play an important role in healthy human homeostasis, either directly or via the microbiome. We have developed an objective, integrated, and automated approach to personalized food and supplement recommendations that is powered by artificial intelligence and individualized molecular data from the gut microbiome, the human host, and their interactions. The process starts with a clinically validated transcriptomic analysis of a person’s stool (and some cases also blood) sample. These molecular data are converted into personalized nutritional recommendations (foods and supplements) using algorithms derived from clinical research studies and domain knowledge. We describe an application of our precision nutrition technology platform to human populations with irritable bowel syndrome (IBS), depression, anxiety, and type 2 diabetes (T2D). In these pilot interventional studies, our precision nutrition program achieved significant improvements in clinical outcomes of IBS (39% for severe IBS), depression (31% for severe depression), anxiety (31% for severe anxiety), and the risk score for T2D (>30% reduction relative to the control arm). These data support the integration of data-driven precision nutrition into the standard of care.

Biomarkers in Acute Myocarditis and Chronic Inflammatory Cardiomyopathy: An Updated Review of the Literature.

Myocarditis is a disease caused by cardiac inflammation that can progress to dilated cardiomyopathy, heart failure, and eventually death. Several etiologies, including autoimmune, drug-induced, and infectious, lead to inflammation, which causes damage to the myocardium, followed by remodeling and fibrosis. Although there has been an increasing understanding of pathophysiology, early and accurate diagnosis, and effective treatment remain challenging due to the high heterogeneity. As a result, many patients have poor prognosis, with those surviving at risk of long-term sequelae. Current diagnostic methods, including imaging and endomyocardial biopsy, are, at times, expensive, invasive, and not always performed early enough to affect disease progression. Therefore, the identification of accurate, cost-effective, and prognostically informative biomarkers is critical for screening and treatment. The review then focuses on the biomarkers currently associated with these conditions, which have been extensively studied via blood tests and imaging techniques. The information within this review was retrieved through extensive literature research conducted on major publicly accessible databases and has been collated and revised by an international panel of experts. The biomarkers discussed in the article have shown great promise in clinical research studies and provide clinicians with essential tools for early diagnosis and improved outcomes.

Defining the landscape of patient harm after osteopathic manipulative treatment: synthesis of an adverse event model.

In the United States, osteopathic manipulative treatment (OMT), is a popular complementary physical health approach for the treatment of neuromusculoskeletal disorders. However, post-OMT adverse events (AEs) are poorly defined in terms of frequency, severity, and temporal evolution. To date, no benchmark for patient safety exists. To improve understanding in this field, we set out to model the landscape of patient harm after OMT. We conducted a comprehensive search of all available primary clinical research studies reporting on the occurrence of post-OMT AEs in nonpregnant, adult outpatients treated by an osteopathic physician in the United States. The methodology of eligible studies was then reviewed to select those containing the minimum required dataset to model the post-OMT AEs. The minimum required dataset consisted of four model parameters: 'post-OMT interval', 'OMT encounters with post-OMT interval assessment', 'AEs preceded by an OMT encounter', and 'AE severity.' We used the dataset extracted from selected studies to calculate a patient safety benchmark defined as the incidence rate of AEs per 100 post-OMT interval-days. From 212 manuscripts that we identified, 118 primary clinical research studies were assessed for eligibility. A total of 23 studies met inclusion criteria for methodological review, of which 13 studies passed and were selected for modeling. Mild AEs were the most frequent, accounting for n = 161/165 (98%) of total AEs observed in the literature. The cumulative incidence of mild AEs was also significantly greater (P = 0.01) than both moderate and severe grades. The benchmark incidence rate was 1.0 AEs per 100 post-OMT interval-days. The majority of post-OMT AEs observed in the primary clinical literature were of mild severity. Modeling of the combined dataset on post-OMT AEs allowed for the derivation of a patient safety benchmark that, to date, has not been established in the field of osteopathic manipulative medicine. Additional research is needed to improve model resolution during the post-OMT period. This work conceptualized a model for identifying and grading post-OMT AEs, which should facilitate future comparisons between institutions in order to continually improve patient safety standards in the field of osteopathic manipulative medicine.

A systematic approach for calibrating a Monte Carlo code to a treatment planning system for obtaining dose, LET, variable proton RBE and out-of-field dose

Objective. While integration of variable relative biological effectiveness (RBE) has not reached full clinical implementation, the importance of having the ability to recalculate proton treatment plans in a flexible, dedicated Monte Carlo (MC) code cannot be understated . Here we provide a step-wise method for calibrating dose from a MC code to a treatment planning system (TPS), to obtain required parameters for calculating linear energy transfer (LET), variable RBE and in general enabling clinical realistic research studies beyond the capabilities of a TPS. Approach. Initially, Pristine Bragg peaks (PBP) were calculated in both the Eclipse TPS and the FLUKA MC code. A rearranged Bortfeld energy-range relation was applied to the initial energy of the beam to fine-tune the range of the MC code at 80% dose level distal to the PBP. The energy spread was adapted by dividing the TPS range by the MC range for dose level 80%–20% distal to the PBP. Density and relative proton stopping power were adjusted by comparing the TPS and MC for different Hounsfield units. To find the relationship of dose per primary particle from the MC to dose per monitor unit in the TPS, integration was applied to the area of the Bragg curve. The calibration was validated for spread-out Bragg peaks (SOBP) in water and patient treatment plans. Following the validation, variable RBE were calculated using established models. Main results. The PBPs ranges were within ± mm threshold, and a maximum of 5.5% difference for the SOBPs was observed. The patient validation showed excellent dose agreement between the TPS and MC, with the greatest differences for the lung tumor patient. Significance. A procedure for calibrating a MC code to a TPS was developed and validated. The procedure enables MC-based calculation of dose, LET, variable RBE, advanced (secondary) particle tracking and more from treatment plans.

Improved Biorepository to Support Sickle Cell Disease Genomics and Clinical Research: A Practical Approach to Link Patient Data and Biospecimens from Muhimbili Sickle Cell Program, Tanzania.

In Africa, sickle cell disease phenotypes' genetic contributors remain understudied due to the dearth of databases that pair biospecimens with demographic and clinical details. The absence of biorepositories in these settings can exacerbate this issue. This article documents the physical verification process of biospecimens in the biorepository, connecting them to patient clinical and demographic data and aiding in the planning of future genomic and clinical research studies' experience from the Muhimbili Sickle Cell Program in Dar es Salaam, Tanzania. The biospecimen database was updated with the current biospecimen position following the physical verification and then mapping this information to its demographic and clinical data using demographic identifiers. The biorepository stored 74,079 biospecimens in three -80°C freezers, including 63,345 from 5159 patients enrolled in the cohort between 2004 and 2016. Patients were identified by a control (first visit), entry (when confirmed sickle cell homozygous), admission (when hospitalized), and follow-up numbers (subsequent visits). Of 63,345 biospecimens, follow-ups were 46,915 (74.06%), control 8067 (12.74%), admission 5517 (8.71%), and entry 2846 (4.49%). Of these registered patients, females were 2521 (48.87%) and males were 2638 (51.13%). The age distribution was 1-59 years, with those older than 18 years being 577 (11.18%) and children 4582 (88.82%) of registered patients. The notable findings during the process include a lack of automated biospecimen checks, laboratory information management system, and tubes with volume calibration; this caused the verification process to be tedious and manual. Biospecimens not linked to clinical and demographic data, date format inconsistencies, and lack of regular updating of a database on exhausted biospecimens and updates when biospecimens are moved between positions within freezers were other findings that were found. A well-organized biorepository plays a crucial role in answering future research questions. Enforcing standard operating procedures and quality control will ensure that laboratory users adhere to the best biospecimen management procedures.

Impact of Medication Reconciliation in Oncology Early Phase Studies: A Drug-Drug Interaction Retrospective Study.

This study aims to investigate the impact of medication reconciliation (MR) conducted by pharmacists before patient enrollment and the initiation of investigational treatments. By implementing MR, the primary objective is to evaluate the extent to which the inclusion of patients with prohibited or not recommended concomitant medications in clinical trials can be significantly reduced. The study included all patients who participated in clinical trials and underwent MR between September 1, 2015, and September 1, 2020. To identify prohibited or monitored drugs, protocols and investigator's brochures provided by the sponsor were meticulously reviewed and taken into consideration. MR was performed for 501 patients, uncovering 35% of the medications they were currently taking. Through the pharmaceutical analysis, a total of 346 drug-drug interactions (DDIs) were identified, of which 188 required monitoring and 158 were strictly prohibited. More than half of the prohibited medications were herbal drugs. A significant portion of these prohibited drugs were discontinued, with only 6% being replaced by suitable alternatives. The implementation of MR played a crucial role in the identification of 51% of the prohibited or monitored drugs that were initially overlooked by oncologists. MR is a highly effective measure aimed at reducing the risk of DDIs with investigational drugs, thereby minimizing protocol deviations and enhancing patient care. Sponsors of clinical trials value its implementation and recognize the substantial benefits it brings to the entire trial process. Consequently, many sponsors willingly provide funding to investigational sites that adopt MR as part of their standard practice, acknowledging its critical role in ensuring patient safety and maintaining data integrity throughout the course of clinical research studies.

Clinical Applications and Review of Acupoint GV-1

The Governing Vessel (GV)-1 acupoint is known as Hou-hai in veterinary medicine and Chang-qiang in humans. Due to the perineum location, the clinical applications for GV-1 are very limited in humans and clinical research studies have also been insufficient compared to other acupoints. In contrast, the GV-1 acupoint in animals is convenient to locate and the results are significant for treating many digestive disorders which include diarrhea and constipation, as well as perianal diseases. Acupuncture at GV-1 can affect the function of many Zang-fu organs and according to both clinical studies and research has important diverse effects. Clinical benefits include treatment of gastrointestinal tract disease, perianal/perineal diseases, retained placenta, childbirth/labor/delivery, anesthesia recovery, epilepsy and behavior/cognition. In the present article, the varied clinical applications and research into the effects of GV-1 will be discussed both in veterinary medicine and human medicine.

Pomegranate effects on the health aspects of women during peri- and postmenopause: A systematic review and meta-analysis.

Pomegranate is widely used to preserve human health and help prevent many kinds of diseases. This study aims to review and assess the effects of pomegranate on women's health during and after menopause. PubMed, Web of science, Cochrane, Scopus, and Google Scholar were searched up to the end of 2022 with no language or study type restriction. All types of clinical research studies (randomized clinical trial [RCT], pre-post, case report, and case series) were included. The Cochrane RoB 2.0 tool was used for quality assessment of RCTs. A summary of intervention's effects for each study was provided by calculating standardized mean differences and accompanying 95% confidence interval using random effect model. Weighted mean differences and heterogeneity between studies were assessed using Hedges's method and Cochran's Q test, respectively. Pomegranate can significantly improve hot flashes severity and menopause symptoms and decrease FSH. It significantly improves high-density lipoprotein but not low-density lipoprotein, body mass index, and weight. Most of our results are inconclusive, and the small sample sizes and the lack of blinding and randomization have led to an increased risk of bias. Pomegranate can decrease menopause symptoms, but more well-designed studies, with bigger sample sizes are needed to establish its other clinical benefits for menopausal women.

Exploring Different Sensor Technologies for Infrasonic Cardiac Monitoring: A Review

Infrasonic cardiac monitoring is a non-invasive technique used to detect and monitor cardiac activity by analysing infrasound waves produced by the heart. This technique has several advantages over traditional methods, including the ability to detect changes in infrasound waves that may indicate abnormalities in cardiac function. Infrasonic cardiac monitoring has been used in clinical settings, research studies, and emergency situations and has the potential to revolutionize the field of cardiology by providing a non-invasive method of detecting and monitoring cardiac activity. While there are some challenges associated with this technique, ongoing research and technological advancements hold promise for addressing these challenges and improving the accuracy, reliability, and accessibility of infrasonic cardiac monitoring. This paper aims to provide an introductory overview of infrasonic cardiac monitoring, including its principles, methods, challenges, and future prospects.

Management of fraudulent participants in online research: Practical recommendations from a randomized controlled feasibility trial.

Fraudulent participation is an escalating concern for online clinical trials and research studies and can have a significant negative impact on findings. We aim to shed light on the risk and to provide practical recommendations for detecting and managing such instances. The FREED-Mobile (FREED-M) study is an online, randomized controlled feasibility trial to assess a digital early intervention for young people (aged 16-25) in England or Wales with eating problems. The trial involved baseline (week 0), post-intervention (week 4), and follow-up (week 12) surveys, alongside weekly modules provided over 4 weeks on the study website. Study completers were compensated with £20 shopping vouchers. Despite the complexity of the trial design, two instances of fraudulent sign-ups occurred in January and March 2023. To counter this, we developed a "fraudulent participants protocol" following internal investigations and discussions with collaborators. The implementation of prevention measures such as reCAPTCHA updates, IP address review, and changes in reimbursement effectively halted further fraudulent sign-ups. Our protocol facilitated the systematic identification and withdrawal of suspected or clear fraudsters and was demonstrably robust at distinguishing between fraudsters and genuine responders. All remote, online trials or studies are at risk of fraudulent participation. Drawing from our experience and existing literature, we offer practical recommendations for researchers considering online recruitment and data collection. Vigilance and the integration of deterrents, and data quality checks into the study design from the outset are advised to safeguard research integrity. Fraudulent participation in digital research can have asignificant impact on research findings, potentially leading to biased resultsand misinformed decisions. We developed an effective protocol for theprevention, identification, and management of fraudulent participants. Bysharing our insights and recommendations, we hope to raise awareness of thisissue and provide other researchers with the knowledge and strategies necessaryto safeguard research integrity moving forward.

Development and initial validation of the Orthotic Patient-Reported Outcomes-Mobility (OPRO-M): An item bank for evaluating mobility of people who use lower-limb orthoses.

Lower limb orthoses (LLOs) are externally-applied leg braces that are designed to improve or maintain mobility in people with a variety of health conditions that affect lower limb function. Clinicians and researchers are therefore often motivated to measure LLO users' mobility to select or assess the effectiveness of these devices. Patient-reported outcome measures (PROMs) can provide insights into important aspects of a LLO user's mobility for these purposes. However, few PROMs are available to measure mobility of LLO users. Those few that exist have issues that may limit their clinical or scientific utility. The objective of this study was to create a population-specific item bank for measuring mobility of LLO users. Previously-developed candidate items were administered in a cross-sectional study to a large national sample of LLO users. Responses from study participants (n = 1036) were calibrated to a graded response statistical model using Item Response Theory methods. A set of 39 items was found to be unidimensional, locally independent, and function without bias due to characteristics unrelated to mobility. The set of final calibrated items, termed the Orthotic Patient-Reported Outcomes-Mobility (OPRO-M) item bank, was evaluated for initial evidence of convergent, divergent, and known groups construct validity. OPRO-M was strongly correlated with existing PROMs designed to measure aspects of physical function. Conversely, OPRO-M was weakly correlated with PROMs that measured unrelated constructs, like sleep disturbance and depression. OPRO-M also showed an ability to differentiate groups with expected mobility differences. Two fixed-length short forms were created from the OPRO-M item bank. Items on the short forms were selected based on statistical and clinical criteria. Collectively, results from this study indicate that OPRO-M can effectively measure mobility of LLO users, and OPRO-M short forms can now be recommended for use in routine clinical practice and research studies.

36 Disparities in General Mental Status Between Lower and Higher SES Ethnically Diverse Older Adults

Objective:To investigate differences in performance on a widely used cognitive screener between community-dwelling older adults from two disparate socioeconomic groups.Participants and Methods:Participants were part of a larger study of cognitive screening in healthy older adults. The total sample (N=79, 69.6% female, 19% White/Caucasian, 12.7% Asian, 43% Latino/a, 25.3% Black/African-American) consisted of community-dwelling adults (Mage=73.1 years [SD=7.2] and Meducation=14.3 years [SD=2.6]) who were initially recruited via social media, flyers, and general community announcements. A lack of ethnic minority participants resulted in a two-year commitment to reach communities of color via visits and provision of health literacy to local religious and community programs. Continuous contact with leaders/gatekeepers helped establish research study credibility and forge a stronger sense of trust among ethnically diverse participants in the greater Houston, TX, area. Testing was initially conducted at the clinical study site. Due to low participation rates among people of color, greater effort was placed on tailored strategies to overcome economic and time constraints (i.e., schedule/time conflicts, lack of transportation, inability to pay for parking). To fit the priorities and needs of the participants, testing was also conducted at their homes (25.3%) and nearby religious and community centers (22.8%). Participants identifying as Latino/a or Black were predominantly recruited and tested at their local community center (as requested by gatekeepers/participants) to increase access to the study, in contrast to Caucasian participants. Median income estimates were used to stratify participants by socioeconomic status (SES) based on zip codes into low SES (L-SES) or high SES (H-SES) groups.Results:Participants from the L-SES group had significantly lower total scores on the MoCA than their H-SES counterparts, t(77J=2.837, p=0.003, g=0.696. The average MoCA total score for participants from the L-SES group was 2.64 points lower. The observed differences in MoCA total score when stratifying by ethnicity may be attributable to differences in education level and SES, which are known risk factors for cognitive impairment and will be further examined upon recruitment completion.Conclusions:Studies have found that ethnically diverse older adults not only encounter more barriers to accessing quality health care but also experience disparities in brain health research. Communities of color comprise a sizeable portion of our older adults but have been traditionally underrepresented in clinical research, limiting the generalizability of research findings to clinical treatment. Socioeconomic deprivation has been identified as one of several barriers to research engagement for people of color, placing ethnic communities at increased risk for under- or misdiagnosis and limited access to medical intervention. Preliminary findings have implications for the recruitment of ethnically diverse groups in clinical research. Given the growing racial and ethnic diversity among the United States population, we must do our due diligence to increase understanding of participation and recruitment barriers for racial/ethnic individuals. Tailored community outreach and engagement strategies may be effective in improving the inclusion of ethnically diverse populations and facilitating recruitment and retention in clinical research studies.

Development of Pharmacovigilance System in India and Paradigm of Pharmacovigilance Research: An Overview.

The drugs are projected to cure, prevent and treat diseases; however, there are also chances of mild or severe adverse drug reactions (ADRs) in the patients. Pharmacovigilance (PV) enhances the approach to safe medicines and healthcare, but integration into public healthcare remains a challenge in many countries. The Pharmacovigilance Programme of India (PvPI) is a nationwide programme launched by the Ministry of Health and Family Welfare (MoHFW), Government of India, on 14 July 2010. It is currently run by the Indian Pharmacopoeia Commission (IPC). Presently, 567 ADR Monitoring Centres (AMC) are functioning under PvPI across India. The Central Drugs Standard Control Organization (CDSCO), under the Directorate General of Health Services (DGHS), and the Ministry of Health, Family & Welfare (MoHFW) Government of India is the National Regulatory Authority (NRA) of India. This review aims to trace the development of PV in India and its status among the top ADR reporting countries, with a focus on the current status of the studied ADR in different regions in India. Among the top 20 countries enthusiastic about sending ICSR per million population between 2015 and 2020, India shares 2% of the total ICSRs in VigiBase. India is now being recognized as a hub of global clinical trials and clinical research studies. Hence, it is the need of the hour in India to have a dynamic PV network system with an efficient and prudent operation method. Nevertheless, in India, PV programs are at an early stage on par with other countries, and only because of underreporting of ADRs. However, in the future, PvPI may appear as a big dashboard for ADR reporting culture in India as it continuously works hard to improve patients and drug safety.

The 29th Annual Prostate Cancer Foundation Scientific Retreat Report.

The 29th Annual Prostate Cancer Foundation (PCF) Scientific Retreat was held from October 27 to 29, 2022, at the Omni La Costa Resort in Carlsbad, CA. This was the first-ever hybrid PCF Retreat. The Annual PCF Scientific Retreat is a prominent international scientific gathering centered on groundbreaking, unpublished, and influential studies in basic, translational, and clinical prostate cancer research. It also covers research from related fields with a strong potential for influencing prostate cancer research and patient care. Key areas of research that were focused on at the 2022 PCF Retreat included: (i) the contributions of molecular and genomic factors to prostate cancer disparities; (ii) novel clinical trial updates; (iii) lessons from primary prostate cancer; (iv) lessons from single-cell studies; (v) genetic, epigenetic, epitranscriptomic and posttranslational mechanisms and clinical heterogeneity in prostate cancer; (vi) biology of neuroendocrine and lineage-plastic prostate cancer; (vii) next generation prostate cancer theranostics and combination therapies; (viii) the biology and therapeutic potential of targeting phosphoinositide 3-kinases pathways; (ix) combining immunomodulatory treatments for prostate cancer; (x) novel gamma delta (γδ) T-cell therapy platforms for oncology; and (xi) lessons from other cancers. This article provides a summary of the presentations from the 2022 PCF Scientific Retreat. By disseminating this knowledge, we hope to enhance our understanding of the present research landscape and guide future strides in both prostate cancer research and patient care.

Evaluation of an Acne Severity Grading Self-Assessment System Suitable for the Thai Population - A Pilot Study.

Patient self-assessment is a potential tool in clinical practice to obtain subjective information of acne severity also in clinical trials to assess the general population in research and epidemiologic studies. The patient self-evaluation of acne severity has not yet been developed in Thailand. We aimed to validate an acne severity grading self-assessment suitable for the Thai population. A pilot study was conducted in 77 volunteers with acne lesions. We developed the Thai Global Evaluation Acne Scale (TGEA) and Thai Global Acne Grading System (TGAGS) by translating and adapting the original version. Patient self-assessment of acne severity was performed in two rounds. A training session about acne was provided to all participants lesions before starting the second round. Reliability between the self-assessment and clinician assessment of acne severity was statistically assessed. For TGEA, 48.05% participants rated their acne severity corresponded with the clinicians (Cohen's kappa coefficient, kappa = 0.26). After receiving the training, 79.22% subjects responded their acne severity corresponded with the clinicians (kappa = 0.66). For TGAGS, 77.92% patients who answered their acne severity corresponded with the clinicians (kappa = 0.52). After receiving the training, 94.80% participants responded their acne severity corresponded with the clinicians (kappa = 0.89). For raw score of the TGAGS, the intraclass correlation coefficient (ICC) during the self-assessment of acne severity compared to the clinician assessments was 0.54 and it increased to 0.79 after the training. Due to the almost perfect reliability, we suggested that TGAGS is a reliable subjective self-assessment of acne severity suitable for the Thai population. The training is essential in enhancing the reliability of this instrument. Our study's findings can facilitate clinical practice and research studies.

2 Clinical Validity and Cut-Off Scores of a Brief Neuropsychological Battery for a Large Rural Population in Community Setting

Objective:There is a dearth of an appropriate standardized tool to assess neuropsychological functions in rural population, which has low literacy rates, are culturally diverse, and have limited access to healthcare resources. The NIREH Neuropsychological Battery for Rural Population (NINB-RP) is a relatively brief and easy-to-administer battery comprising multiple tests that are modified or adopted as per rural community settings to evaluate verbal learning, fine coordination, attention efficiency, executive task, concentration, and visual attention, mental flexibility, and motor coordination in rural populations. The present study aimed to examine the clinical validity and establish cut-off scores for impairment of neuropsychological functions for different age, gender, and education levels of NINB-RP in a rural community in central India.Participants and Methods:This was a prospective cross-sectional study conducted in participants aged > 18 years (n=2952, M: F=1407:1545) recruited through a stratified sampling technique from 23 randomly selected villages from central India. The data of nine neuropsychological tests [(Finger and Tweezer dexterity test (FDT, TDT); Digit Forward and Backward test (DFT, DBT); Serial subtraction test (SST); Trail Making-A and B; Finger Tapping test (FTT); and Letter Digit Substitution test, LDST)] from 215 cognitively impaired and 2737 healthy control subjects were analyzed. The tests were performed in a village school/community hall or an outdoor camp. Independent sample t-test, Chi-square test, and Receiver Operating Characteristic (ROC) curve were used to calculate the area under the curve (AUC), cut-off scores, and sensitivity (ST)/specificity (SP) values for seven conditions, i.e., gender (male vs. female), age groups (up to 49 years and above 50 years); and educational levels (illiterate, intermediate and college). For those variables where ST/SP values were lower than 0.70, a unique cut-off score was calculated for the entire sample, adjusting by age and educational levels.Results:A significant difference in mean (median) scores between the healthy control and cognitively impaired groups were observed in all tests except Trail Making A and B and LDST. The AUC for most of the tests ranged from 0.70 to 0.81, and the ST/SP values ranged from 69-73% and 65-75%, respectively. The results showed that most tests of NINB-RP reached moderate to good sensitivity and specificity for gender, age and education levels, except for DBT for females, above 50 years, and illiterate and intermediate education groups. FDT for males [AUC: 0.85 (95%CI0.80-0.91], ST/SP=76/82%] and females [(AUC=0.78 (95%CI0.74-0.82), ST/SP=71/70%], TDT for intermediate education group [AUC=0.82 (95%CI0.60-1.00), ST/SP=86/83%] and FTT for less than 49 years age group [AUC=0.75 (95%CI0.67-0.84), ST/SP=71/76%] were the most useful tests to discriminate among healthy control and cognitively impaired rural population.Conclusions:The present study is an attempt to establish the cut-off scores of a neuropsychological battery for a large rural population in the community setting. The proposed cut-off values might be helpful in clinical assessment in rural areas where clinical neuropsychology services are not readily available. NINB-RP can be a valuable tool for clinical research studies in rural communities. Further studies on similar samples in other countries need to be undertaken.

72 Bringing Neuropsychology to the Community: Adaptation of a Rey Osterreith Complex Figure Scoring System for Use in Large-Scale Community-Based Clinical Trials

Objective:The Rey Osterreith Complex Figure (ROCF) is a neuropsychological task used to measure visual-motor integration, visual memory, and executive functioning (EF) in autistic youth. The ROCF is a valued clinical tool because it provides an insight into the way an individual approaches and organizes complex visual stimuli. The constructs measured by the ROCF such as planning, organization, and working memory are highly relevant for research in, but the standardized procedures for scoring the ROCF can be challenging to implement in large scale clinical trials due to complex and lengthy scoring rubrics. We present preliminary data on an adaptation to an existing scoring system that provides quantifiable scores, can be implemented with reliability, and reduces scoring time.Participants and Methods:Data was taken from two large-scale clinical trials focusing on EF in autistic youth. All participants completed the ROCF following standard administration guidelines. The research team reviewed commonly used scoring systems and determined that the Boston Qualitative Scoring System (BQSS) was the best fit due to its strengths in measuring EF, the process-related variables generated, and the available normative data. Initially, the BQSS full scoring system was used, which resulted in comprehensive scores but was not feasible due to the time required (approximately 1-1.5 hours per figure for research assistants to complete scoring). Then, the BQSS short form was used, which was successful at solving the timing problem, but resulted in greater subjectivity in the scores impacting the team’s ability to become reliable. Independent reliability could not be calculated for this version because of the large number of discrepancies among scorers which included 2 neuropsychologists and 4 research assistants. A novel checklist was then developed that combined aspects of both scoring systems to help promote objectivity and reliability. In combination with this checklist the team created weekly check in meetings where challenging figures could be brought to discuss. Independent reliability was calculated amongst all research assistant team members (n=4) for the short form and novel checklist. Reliability was calculated based on (1) if the drawing qualified for being brought to the whole team and (2) individual scores on the checklist.Results:Independent reliability was calculated for 10 figures scored utilizing the novel checklist by a team of 4 trained research assistants. All scorers were able to achieve 80% reliability with a high average (80-86%). Study team members reported that scoring took less time taking on average 30-45 minutes per figure.Conclusions:Inter-rater reliability was strong on the checklist the study team created, indicating its potential as a useful adaptation to the BQSS scoring system that reduces time demands, making the tool feasible for use in large-scale clinical research studies with initially positive reliability factors. The checklist was easy to use, required little training and could be completed quickly. Future research should continue to examine the reliability of the checklist and the time it takes to complete. Additionally, the ROCF should be studied more broadly in research and examined as a potential outcome measure for large scale research studies.

Clinical research in hospital pharmacy during the fight against COVID-19

The health crisis resulting from the rapid spread of SARS-CoV-2 worlwi-de, added to the low evidence of currently used treatments has led to the development of a large number of clinical trials (CT) and observational studies. Likewise, important measures have been adopted in healthcare and research centers aimed at halting the pandemic as soon as possible.The objective of this study is to gather the main aspects of the clinical research studies undertaken by the Pharmacy Department (PD) of Spain during the COVID-19 crisis.The decision of the Spanish Society of Hospital Pharmacy (SEFH) to sponsor CTs made it possible that 13% of Pharmacy Department (PD) had been led at least one CT. The Spanish Agency for Medicines and Medical Devices (AEMPS), in coordination with Institutional Review Boards, has adopted a fast-track review procedure to accelerate authorizations for CTs related to the treatment or prevention of COVID-19. There have also been numerous public and private calls for financing research projects aimed at contributing to the fight against this virus.Despite the pandemic, actions have been taken to continue ongoing CTs and studies while the safety and well-being of patients are guaranteed. More specifically, the AEMPS and the European Medicines Agency (EMA) have issued guidelines that incorporate changes to CT protocols that will have to be applied until the pandemic is over.In this health emergency, the scientific community has found itself in a race against time to generate evidence. It is at this moment that hospital pharmacists emerge as key players in clinical research and are contributing to a rational, effective and safe healthcare decision-making.