Drug Development Clinical Trials Research Articles

Test-retest and interrater reliability of experimental within-subject variability of pain reports as assessed by the focused analgesia selection test.

Within-subject variability (WSV) of pain intensity reports has been shown to predict the placebo response. The focused analgesia selection test (FAST), which allows to experimentally assess WSV of pain reports, has been used as a screening tool to identify participants who are likely to have a strong placebo response in drug-development clinical trials. Yet, the reliability of FAST has not been reported. To assess test-retest and interrater reliability of the FAST outcomes. To mimic pharma-sponsored clinical trials, we enlisted inexperienced assessors who underwent limited training. Healthy volunteers performed the FAST twice within a week and were randomly assigned to either the test-retest group or the interrater group. T-tests, partial Pearson correlations, intraclass correlations (ICC), and Bland-Altman plots were generated to assess FAST outcomes' reliability. Sixty-three participants completed the study and were assigned to the test-retest (N = 33) or interrater (N = 30) arms. No statistically significant differences in the FAST outcomes were detected between the 2 sessions, except for the FAST covariance (FAST CoV) in the interrater assessment (P = 0.009). Test-retest reliabilities of the FAST-main outcomes were r = 0.461, ICC = 0.385 for the FAST R 2 and r = 0.605, ICC = 0.539 for the FAST ICC and in the interrater cohort, they were FAST R 2: r = 0.321, ICC = 0.337 and FAST ICC: r = 0.355, ICC = 0.330. Using inexperienced assessors, the FAST outcomes test-retest ranged from moderate to strong, whereas the interrater reliability ranged from weak to poor. These results highlight the importance of adequately training study staff members before using this tool in multicentre clinical trials.

Regulatory compliance and readability of informed consent forms in industry-sponsored drug development clinical trials.

An informed consent form is essential in drug development clinical trials. This study aimed to evaluate regulatory compliance and readability of informed consent forms currently being used in industry-sponsored drug development clinical trials. This descriptive, cross-sectional study evaluated the informed consent forms of industry-sponsored drug development clinical trials conducted at the Faculty of Medicine, Chiang Mai University, between 2019 and 2020. The informed consent form's compliance with the three major ethical guidelines and regulations (i.e. International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use E6(R2) Good Clinical Practice; Declaration of Helsinki; and the revised Common Rule) were analyzed. The document length and the readability scores (using Flesch Reading Ease and Flesch-Kincaid Reading Grade) were assessed. Of 64 reviewed informed consent forms, the average page length was 22.0 ± 7.4 pages. More than half of their length was mainly devoted to three elements: trial procedures (22.9%), risks and discomforts (19.1%), and confidentiality and the limit of confidentiality (10.1%). Although most of the required elements of the informed consent form content were included in most informed consent forms, we identified four elements with often missing information in the form: aspects of research that are experimental (n = 43, 67.2%), involvement of whole-genome sequencing (n = 35, 54.7%), commercial profit sharing (n = 31, 48.4%), and posttrial provisions (n = 28, 43.8%). The informed consent forms in industry-sponsored drug development clinical trials were long but incomplete. Our findings draw attention to ongoing challenges in industry-sponsored drug development clinical trials, where deficient informed consent form quality continues to exist.

Reviews of drug candidates for COVID-19

The Outbreak of coronavirus disease 2019 (COVID-19) has become a global pandemic since December 2019. In order to combat the COVID-19, researchers have carried out many related experiments, including the pathogenesis of virus, to understand the structure and mechanism of the novel coronavirus. In addition, they have conducted in vitro and clinical trials for drug development. In this paper, the possible drug targets are discussed from the perspective of inhibiting virus entry into cells and inhibiting virus replication. In addition, the structure of the virus and its mechanism of entry into host cells are reviewed. Through this review, drug researchers can have a comprehensive understanding of the potential targets being investigated.

European Union Regulation on clinical trials and Regulation on medical devices: A common soil for future development

The recent European Union (EU) Regulations on clinical trial on medicinal products (MPs) (2014/536) and on medical devices (MD) (2017/745) represent potential improvement for the European health system and may offer advantages to the citizens. As Regulations, they are immediately applicable in Member States overruling national laws, being an advantage for stakeholders (e.g. sponsors and investigators) and Europe becomes de facto one homogeneous place for research and development of medicines and medical devices. This perspective commentary focuses on the most relevant methodological and regulatory aspects of the recent Regulation on clinical trials for drug development and how it may indirectly impact on substance-based medical devices (SBMD). The article highlights the innovations associated with the 2017/745 Regulation, especially to the area of SBMD, which represent a novelty among MDs. Since SBMDs share some aspects of medicines, they will increasingly undergo research in the future related to the performance and safety claims, via post-marketing surveillance. Importantly, SBMD’s Consumers are rapidly increasing due to their usage to treat some common symptoms, which not necessarily need conventional medicines. “Frontiers in Drug Safety and Regulation” created a section to reflect this rapidly-changing scenario and host reports on SBMD in a scientific environment. This initiative is also a reflection of the recent regulation on SBMDs. Thus, the improvement of clinical research through the new EU Regulation on clinical trials may become useful also to the new requirements for SBMD. A novel editorial initiative will further contribute to implement the EU Regulation providing adequate scientific dissemination.

Regulatory and Clinical Expert Perspective of the 2022 FDA Draft Guidance “Celiac Disease: Developing Drugs for Adjunctive Treatment to a Gluten-Free Diet”

Regulatory and Clinical Expert Perspective of the 2022 FDA Draft Guidance “Celiac Disease: Developing Drugs for Adjunctive Treatment to a Gluten-Free Diet”

Secukinumab is effective in the treatment of recalcitrant palmoplantar psoriasis and palmoplantar pustular psoriasis in a daily practice setting

Secukinumab is effective in the treatment of recalcitrant palmoplantar psoriasis and palmoplantar pustular psoriasis in a daily practice setting

Clinical Trial in a Dish for Space Radiation Countermeasure Discovery

NASA aims to return humans to the moon within the next five years and to land humans on Mars in a few decades. Space radiation exposure represents a major challenge to astronauts’ health during long-duration missions, as it is linked to increased risks of cancer, cardiovascular dysfunctions, central nervous system (CNS) impairment, and other negative outcomes. Characterization of radiation health effects and developing corresponding countermeasures are high priorities for the preparation of long duration space travel. Due to limitations of animal and cell models, the development of novel physiologically relevant radiation models is needed to better predict these individual risks and bridge gaps between preclinical testing and clinical trials in drug development. “Clinical Trial in a Dish” (CTiD) is now possible with the use of human induced pluripotent stem cells (hiPSCs), offering a powerful tool for drug safety or efficacy testing using patient-specific cell models. Here we review the development and applications of CTiD for space radiation biology and countermeasure studies, focusing on progress made in the past decade.

Underrepresentation of Minorities and Lack of Race Reporting in Ulcerative Colitis Drug Development Clinical Trials.

Lay Summary Historically, inflammatory bowel disease trials report high rates of White patients enrollment. To promote initiatives toward diversifying the enrolled population, we assessed the reporting of race and ethnicity of patients enrolled in pharmaceutical clinical trials for ulcerative colitis.

P404 Underrepresentation of minorities and lack of race reporting in ulcerative colitis drug development clinical trials

Abstract Background Historically, inflammatory bowel disease (IBD) trials report high enrollment rates for white-caucasian patients. To promote initiatives towards diversifying patients enrolled in clinical trials, we assessed the reporting of race/ethnicity of patients enrolled in pharmaceutical clinical trials for ulcerative colitis (UC). Methods A previous systematic review of all placebo-controlled trials in adult patients with UC examining different therapeutic drug classes was performed from inception to December 2020. Trial and patient characteristics were summarized according to the type of variable. Categorical variables were summarized by displaying the number and percentage of trials or participants for each category. Continuous variables were summarized by displaying the weighted mean, weighted standard deviation, and range. Means and standard deviations (SD) were weighted by the number of participants in each trial. Results Descriptive statistics of trial and patient characteristics for, 95 induction trials and, 29 maintenance trials are summarized in Table, 1. Race was reported in, 37.9% (36/95) of induction studies, with most participants being White (86.3%;, 8610/9976). Furthermore, 21/36 (58.3%) studies reported race as White vs. non-White participants; and, 15/36 (41.7%) studies provided further breakdown, including Black (115/3414 patients [3.4%]), Asian (448/4136 patients [10.8%]), and “Other” (127/4136 patients [3.1%]). Moreover, 3/36 studies misreported race as ethnicity and, only, 3/36 studies reported ethnicities correctly, classifying patients as Hispanic/Latinx vs. Non-Hispanic/Latinx. For maintenance trials, 34.5% (10/29) studies reported race, with majority of participants being White (85.6%;, 2778/3246). Additionally, 6/10 studies reported only a White vs. non-White participants comparison, while, 4/10 reported other races, including Black (45/1145 patients [3.9%]), Asian (40/888 patients [4.5%]), and “Other” (26/1145 patients [2.3%]). No studies reported ethnicity. Conclusion Given the increasing burden of IBD in developing countries, differences amongst racial and ethnic groups are important to understand since they can influence disease phenotype, response to therapy, and safety outcomes.1 We found poor race reporting in UC clinical trials and observed that the vast majority of participants enrolled were White. These findings suggest that the population prevalence of UC amongst different racial groups is not reflected in clinical trial populations, being important to raise awareness of the existing barriers that prevent patients from accessing clinical trials. Reporting of race and ethnicity in UC clinical trials should be mandatory, and a requirement to enroll a certain percentage of non-White patients should be considered.2

Testing in the workplace: finding a path through a pandemic.

Testing in the workplace: finding a path through a pandemic.

Home-based Digital Assessments with Applied Sentiment & Emotion AI Capture Improved Quality-of-life in Asthma Patients.

With the rise of digital transformation in the pharmaceutical industry, digital therapeutics are being integrated in drug development clinical trials. In the TWINKLE study, information about asthmatic patients' disease control and quality-of-life (QoL) was measured by daily video recording, in conjunction with daily electronic questionnaires and home-based spirometry. From the video messages, sentiment and emotion AI was applied to detect subtle QoL changes in asthmatic patients after receiving treatments. Sentiment scores, derived from patients' daily messages via natural language processing, correlated strongly with metrics of lung functions and outcomes of electronic questionnaires. However, video-derived emotional analysis exhibited strong interpersonal variations and systematic biases, yet still showed utility in detecting QoL changes after personalized calibration and signal aggregation. Compared to traditional patient-reported outcomes, all three categories of digital measurements were able to detect significantly improved asthma control from patients who responded to treatments. The result provides insights into developing novel digital outcomes through the application of connected digital devices and advanced AI tailored to clinical settings.Clinical relevance- Digital outcomes involving connected digital devices and AI for sentiment/emotion analysis could capture subtle QoL changes reliably and earlier than hospital visits, reducing burden and improving disease management. Integrating digital therapeutics in asthma drug development trials may prove to be feasible and valuable.

Adaptive dose-response studies to establish proof-of-concept in learning-phase clinical trials.

In learning-phase clinical trials in drug development, adaptive designs can be efficient and highly informative when used appropriately. In this article, we extend the multiple comparison procedures with modeling techniques (MCP-Mod) procedure with generalized multiple contrast tests (GMCTs) to two-stage adaptive designs for establishing proof-of-concept. The results of an interim analysis of first-stage data are used to adapt the candidate dose-response models and the dosages studied in the second stage. GMCTs are used in both stages to obtain stage-wise -values, which are then combined to determine an overall -value. An alternative approach is also considered that combines the -statistics across stages, employing the conditional rejection probability principle to preserve the Type I error probability. Simulation studies demonstrate that the adaptive designs are advantageous compared to the corresponding tests in a nonadaptive design if the selection of the candidate set of dose-response models is not well informed by evidence from preclinical and early-phasestudies.

Microbiome recovery in adult females with uncomplicated urinary tract infections in a randomised phase 2A trial of the novel antibiotic gepotidacin (GSK2140944)

BackgroundWith increasing concerns about the impact of frequent antibiotic usage on the human microbiome, it is important to characterize the potential for such effects in early antibiotic drug development clinical trials. In a randomised Phase 2a clinical trial study that evaluated the pharmacokinetics of repeated oral doses of gepotidacin, a first-in-chemical-class triazaacenaphthylene antibiotic with a distinct mechanism of action, in adult females with uncomplicated urinary tract infections for gepotidacin (GSK2140944) we evaluated the potential changes in microbiome composition across multiple time points and body-sites (ClinicalTrials.gov: NCT03568942).ResultsSamples of gastrointestinal tract (GIT), pharyngeal cavity and vaginal microbiota were collected with consent from 22 patients at three time points relative to the gepotidacin dosing regimen; Day 1 (pre-dose), Day 5 (end of dosing) and Follow-up (Day 28 ± 3 days). Microbiota composition was determined by DNA sequencing of 16S rRNA gene variable region 4 amplicons. By Day 5, significant changes were observed in the microbiome diversity relative to pre-dose across the tested body-sites. However, by the Follow-up visit, microbiome diversity changes were reverted to compositions comparable to Day 1. The greatest range of microbiome changes by body-site were GIT followed by the pharyngeal cavity then vagina. In Follow-up visit samples we found no statistically significant occurrences of pathogenic taxa.ConclusionOur findings suggest that gepotidacin alteration of the human microbiome after 5 days of dosing is temporary and rebound to pre-dosing states is evident within the first month post-treatment. We recommend that future antibiotic drug trials include similar exploratory investigations into the duration and context of microbiome modification and recovery.Trial registrationNCT03568942. Registered 26 June 2018.

Glibenclamide Treatment in Traumatic Brain Injury: Operation Brain Trauma Therapy.

Glibenclamide (GLY) is the sixth drug tested by the Operation Brain Trauma Therapy (OBTT) consortium based on substantial pre-clinical evidence of benefit in traumatic brain injury (TBI). Adult Sprague-Dawley rats underwent fluid percussion injury (FPI; n = 45), controlled cortical impact (CCI; n = 30), or penetrating ballistic-like brain injury (PBBI; n = 36). Efficacy of GLY treatment (10-μg/kg intraperitoneal loading dose at 10 min post-injury, followed by a continuous 7-day subcutaneous infusion [0.2 μg/h]) on motor, cognitive, neuropathological, and biomarker outcomes was assessed across models. GLY improved motor outcome versus vehicle in FPI (cylinder task, p < 0.05) and CCI (beam balance, p < 0.05; beam walk, p < 0.05). In FPI, GLY did not benefit any other outcome, whereas in CCI, it reduced 21-day lesion volume versus vehicle (p < 0.05). On Morris water maze testing in CCI, GLY worsened performance on hidden platform latency testing versus sham (p < 0.05), but not versus TBI vehicle. In PBBI, GLY did not improve any outcome. Blood levels of glial fibrillary acidic protein and ubiquitin carboxyl terminal hydrolase-1 at 24 h did not show significant treatment-induced changes. In summary, GLY showed the greatest benefit in CCI, with positive effects on motor and neuropathological outcomes. GLY is the second-highest-scoring agent overall tested by OBTT and the only drug to reduce lesion volume after CCI. Our findings suggest that leveraging the use of a TBI model-based phenotype to guide treatment (i.e., GLY in contusion) might represent a strategic choice to accelerate drug development in clinical trials and, ultimately, achieve precision medicine in TBI.

Updating the Clinical Picture of Facioscapulohumeral Muscular Dystrophy: Ramifications for Drug Development With Potential Solutions.

Facioscapulohumeral muscular dystrophy (FSHD) is a complex, inheritable, and rare muscle disease that affects the entire body. The major symptom of FSHD is progressive weakening and loss of skeletal muscles. The usual location of these weaknesses at onset is the origin of the name: face (facio), shoulder girdle (scapulo), and upper arms (humeral). FSHD appears to have varying molecular and genetic determinants with commensurate differences in disease progression. Facioscapulohumeral muscular dystrophy (MD) is probably the most prevalent form of MD but has neither disease-modifying treatments nor a cure. As the mechanism of action becomes further elucidated, more biopharmaceutical companies are investing capital into finding treatments for patients with FSHD. Sponsors of treatments for FSHD patients should be aware of some of the common misconceptions associated with FSHD drug development with the goal of optimizing the chance to prove safety and efficacy for each potential treatment for FSHD in the clinical trial setting. Four major topics with potential clinical manifestations for patients with FSHD will be discussed related to muscle weakness, respiratory issues, animal models and prevalence. The authors offer multiple solutions to help counteract misconceptions with each scenario during clinical trial drug development.

Patient-Reported Outcomes in Online Communications on Statins, Memory, and Cognition: Qualitative Analysis Using Online Communities.

BackgroundIn drug development clinical trials, there is a need for balance between restricting variables by setting eligibility criteria and representing the broader patient population that may use a product once it is approved. Similarly, although recent policy initiatives focusing on the inclusion of historically underrepresented groups are being implemented, barriers still remain. These limitations of clinical trials may mask potential product benefits and side effects. To bridge these gaps, online communication in health communities may serve as an additional population signal for drug side effects.ObjectiveThe aim of this study was to employ a nontraditional dataset to identify drug side-effect signals. The study was designed to apply both natural language processing (NLP) technology and hands-on linguistic analysis to a set of online posts from known statin users to (1) identify any underlying crossover between the use of statins and impairment of memory or cognition and (2) obtain patient lexicon in their descriptions of experiences with statin medications and memory changes.MethodsResearchers utilized user-generated content on Inspire, looking at over 11 million posts across Inspire. Posts were written by patients and caregivers belonging to a variety of communities on Inspire. After identifying these posts, researchers used NLP and hands-on linguistic analysis to draw and expand upon correlations among statin use, memory, and cognition.ResultsNLP analysis of posts identified statistical correlations between statin users and the discussion of memory impairment, which were not observed in control groups. NLP found that, out of all members on Inspire, 3.1% had posted about memory or cognition. In a control group of those who had posted about TNF inhibitors, 6.2% had also posted about memory and cognition. In comparison, of all those who had posted about a statin medication, 22.6% (P<.001) also posted about memory and cognition. Furthermore, linguistic analysis of a sample of posts provided themes and context to these statistical findings. By looking at posts from statin users about memory, four key themes were found and described in detail in the data: memory loss, aphasia, cognitive impairment, and emotional change.ConclusionsCorrelations from this study point to a need for further research on the impact of statins on memory and cognition. Furthermore, when using nontraditional datasets, such as online communities, NLP and linguistic methodologies broaden the population for identifying side-effect signals. For side effects such as those on memory and cognition, where self-reporting may be unreliable, these methods can provide another avenue to inform patients, providers, and the Food and Drug Administration.

Bispecific T-Cell Engager (BiTE) Antibody Based Immunotherapy for Treatment of Relapsed Refractory Multiple Myeloma (RRMM): A Systematic Review of Preclinical and Clinical Trials

Introduction Bispecific T-cell engager (BiTE) antibodies represent a novel therapeutic option for patients with multiple myeloma (MM). BiTE antibodies lack Fc region, and have variable domain only, they can simultaneously bind to two different epitopes i.e. cluster of differentiation 3 (CD3) molecules on tumor-specific T cells, and a specific antigen on myeloma cells, which leads to T-cell dependent destruction of myeloma cells. Currently, blinatumomab, specific for CD3 and CD19 is the only Food and Drug Administration FDA approved BiTE antibody for clinical use in patients with relapsed/refractory (RR) B-cell acute lymphoblastic leukemia, several similar BiTE antibodies are under development. Methods Following PRISMA guidelines, we performed comprehensive literature on 4/15/19 cross-referencing the terms "bispecific antibodies" and "multiple myeloma" using PubMed, Embase, Web of Science, Cochrane Library, Clinicaltrials.gov and review of international medical meeting abstracts. Initially, 256 articles were identified and after detailed scrutiny, one phase 1 clinical trial with prelim results, 4 preclinical and 4 ongoing clinical trials were included. Results Preclinical trials: Anti-BCMA x Anti-CD3 Bispecific Antibody: BiTE antibodies are still in early development in MM, and most of the published data is about the pre-clinical phase. In preclinical trials, Hipp et al. 2017 and Cho et al. 2018 reported that AMG 420 (BI 836909) and AMG 701, which are anti CD3 and B-cell maturation antigen (BCMA), are highly efficacious in vitro in the killing of myeloma cells and potently induces autologous tumor cell lysis in patients with both newly diagnosed and RRMM regardless of their disease status. In mouse xenograft models reconstituted with human T cells, in vivo efficacy of AMG 420 was reported with an overall response in 6 of 10 animals, with all 6 responders became tumor-free at the end of the study. In an orthotopic L-363 xenograft model, treatment with AMG 420 resulted in prolonged median survival of 43-43.5 days. Dilillo et al. 2018 and Ji Li et al. 2017 reported similar in vivo results for REGN5458 and BFCR4350A respectively. Clinical trials: Currently, there are 5 phase 1 ongoing clinical trials (Table 1). Updated results of only first in human phase I AMG 420 are available. Forty-two MM patients with a high tumor burden and four prior lines of therapy were given 2.5 treatment cycles with AMG 420. Overall thirteen (31%) patients responded to AMG 420 therapy, with complete response (CR) in 6 (14.2%) patients, very good partial response (VGPR) in 2 (5%) patients and partial response (PR) in 2(5%) patients. Eleven of these patients responded in the first treatment cycle, with a median response time of 1 month. Twenty-five (57.1%) patients discontinued treatment due to progressive disease. Four deaths were reported; 2 from disease progression and 2 due to adverse events; neither of them was treatment-related. Serious adverse events were reported in twenty-one (50%) patients, the infection was reported in twelve (29%) and polyneuropathy in three (7%), eighteen (43%) required hospitalization. Treatment-related serious adverse events included three (7%) patients with grade 2-3 cytokine release syndrome, three (7%) with polyneuropathy and one (2.3%) with edema. Conclusion After the success of naked antibodies like daratumumab and elotuzumab for MM, there is a need to develop immunotherapy using conjugated antibodies and BiTE antibodies to overcome the challenge of MM resistance and relapse to prior therapies. Preclinical data with BiTE antibodies are promising; AMG 420 anti-CD3/BCMA BiTE has already been granted fast track status by the FDA. We anticipate that drug will enter phase 2 clinical trials for drug development against RRMM Other BiTE antibodies with strong preclinical efficacy are under development and data from larger prospective clinical trials is needed to explore their efficacy in the treatment of multiple myeloma. Table 1 Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

Next-Generation DILI Biomarkers: Prioritization of Biomarkers for Qualification and Best Practices for Biospecimen Collection in Drug Development.

The diagnosis and management of drug‐induced liver injury (DILI) remains a challenge in clinical trials in drug development. The qualification of emerging biomarkers capable of predicting DILI soon after the initiation of treatment, differentiating DILI from underlying liver disease, identifying the causal entity, and assigning appropriate treatment options after DILI is diagnosed are needed. Qualification efforts have been hindered by lack of properly stored and consented biospecimens that are linked to clinical data relevant to a specific context of use. Recommendations are made for biospecimen collection procedures, with the focus on clinical trials, and for specific emerging biomarkers to focus qualification efforts.

Probability monitoring procedures for sample size determination

ABSTRACTIn clinical research, power analysis is often performed for sample size calculation. The purpose is to achieve a desired power of correctly detecting a clinically meaningful difference at a pre-specified level of significance if such a difference truly exists. However, in some situations such as (i) clinical trials with extremely low incidence rates and (ii) for rare disease drug development clinical trials, power analysis for sample size calculation may not be feasible because (i) it may require a huge sample size for detecting a relatively small difference and (ii) eligible patients may not be available for a small target patient population. In these cases, other procedures for sample size determination with certain statistical assurance are needed. In this article, an innovative method based on a probability monitoring procedure is proposed for sample size determination. The concept is to select an appropriate sample size for controlling the probability of crossing safety and/or efficacy boundaries. For rare disease clinical development, an adaptive probability monitoring procedure may be applied if a multiple-stage adaptive trial design is used.

Updating the Clinical Picture of Facioscapulohumeral Muscular Dystrophy: Ramifications for Drug Development With Potential Solutions

Facioscapulohumeral muscular dystrophy (FSHD) is a complex, inheritable, and rare muscle disease that affects the entire body. The major symptom of FSHD is progressive weakening and loss of skeletal muscles. The usual location of these weaknesses at onset is the origin of the name: face (facio), shoulder girdle (scapulo), and upper arms (humeral). FSHD appears to have varying molecular and genetic determinants with commensurate differences in disease progression. Facioscapulohumeral muscular dystrophy (MD) is probably the most prevalent form of MD but has neither disease-modifying treatments nor a cure. As the mechanism of action becomes further elucidated, more biopharmaceutical companies are investing capital into finding treatments for patients with FSHD. Sponsors of treatments for FSHD patients should be aware of some of the common misconceptions associated with FSHD drug development with the goal of optimizing the chance to prove safety and efficacy for each potential treatment for FSHD in the clinical trial setting. Four major topics with potential clinical manifestations for patients with FSHD will be discussed related to muscle weakness, respiratory issues, animal models and prevalence. The authors offer multiple solutions to help counteract misconceptions with each scenario during clinical trial drug development.