Pharmaceutical Clinical Trials Research Articles

Impact of Contract Research Organizations on Pharmaceutical Industries: A Review

Abstract: Contract Research Organizations are bodies that offer research and development services on a contract basis to the pharmaceutical, biotechnology, medical device, and other industries. These organizations offer a wide range of services to support the drug discovery, development, and commercialization process. Initially, CROs begin with clinical trial management facilities and assisting sponsors with clinical study design, whereas laboratory CROs provide drug discovery, manufacturing, and bioanalytical services, including site feasibility. Their services mainly cover pharmaceutical and biotechnology industry based work such as drug development, pharmaceutical product development, clinical and preclinical trials, analytical method developments, pharmacovigilance, medical writing, etc. India presents itself as a wonderful platform for CROs attributing to its huge population, varied disease conditions, accessible human resources, large number of hospitals and low treatment cost. In the clinical trial process, CROs are engaged by the sponsor to accomplish a number of duties, taking into account various administrative and technical responsibilities on behalf of the sponsor. The current manuscript highlights the globalization of clinical trials, the concept of CRO, roles and responsibilities, functions of CROs, regulatory infrastructure of CRO, criteria for selection of suitable CRO, Indian CRO market and impact of Covid-19 pandemic on it.

A Call for Innovative Translational and Clinical Research to Address China's Unique Cancer Landscape.

The Chinese government has, in recent decades, implemented various administrative laws and regulatory policies to expedite cancer therapeutic development, boosting research and development pipelines for domestic pharmaceutical companies and clinical trials; however, China faces unique challenges given the high prevalence of certain cancer types and distinct disease burdens, some of which are frequently overlooked by international pharmaceutical companies. Given the substantial unmet need for China-specific cancer care, it is crucial to promote the development of innovative pharmaceutical and clinical research in China, with a particular emphasis on addressing tumors most prevalent in its population.

Genetic Panel Reveals Coexisting Neuromuscular Disorders in Patients With Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy is a genetically based neuromuscular disorder characterized by progressive physical impairment and cardiomyopathy in children, leading to fatal cardiac or respiratory failure. Duchenne muscular dystrophy shares some overlapping clinical features with other disorders, complicating clinical differentiation. We hypothesized that some Duchenne muscular dystrophy patients may have a secondary neuromuscular disorders that could negatively skew data during pharmaceutical clinical trials and lead to incomplete treatment plans. Consecutive genetic panels on 353 patients were reviewed. Thirty-two (32; 9.1%) patients with Duchenne muscular dystrophy were identified. Three (3; 9.4%) were found to have at least 1 genetically confirmed secondary neuromuscular disorder. Overlooking these coexisting disorders could lead to unexpected treatment failures, potentially affecting medication efficacy in trials or commercial use. Secondary neuromuscular disorders should be considered in Duchenne muscular dystrophy patients before clinical trial enrollment or treatment planning, with expanded genetic testing, such as whole exome sequencing or whole genome sequencing, likely to reveal even more secondary disorders.

Flaxseed (Linum usitatissimum) mucilage: A versatile stimuli–responsive functional biomaterial for pharmaceuticals and healthcare

The present review is novel as it discusses the main findings of researchers on the topic and their implications, as well as highlights the emerging research in this particular area and its future prospective. The seeds of Flax (Linum usitatissimum) extrude mucilage (FSM) that has a diverse and wide range of applications, especially in the food industry and as a pharmaceutical ingredient. FSM has been blended with several food and dairy products to improve gelling ability, optical properties, taste, and user compliance. The FSM is recognized as a foaming, encapsulating, emulsifying, suspending, film–forming, and gelling agent for several pharmaceutical preparations and healthcare materials. Owing to stimuli (pH) –responsive swelling–deswelling characteristics, high swelling indices at different physiological pHs of the human body, and biocompatibility, FSM is considered a smart material for intelligent, targeted, and controlled drug delivery applications through conventional and advanced drug delivery systems. FSM has been modified through carboxymethylation, acetylation, copolymerization, and electrostatic complexation to get the desired properties for pharma, food, and healthcare products. The present review is therefore devoted to the isolation techniques, structural characterization, highly valuable properties for food and pharmaceutical industries, preclinical and clinical trials, pharmacological aspects, biomedical attributes, and patents of FSM.

ESR Essentials: response assessment criteria in oncologic imaging-practice recommendations by the European Society of Oncologic Imaging.

Assessing the response to oncological treatments is paramount for determining the prognosis and defining the best treatment for each patient. Several biomarkers, including imaging, can be used, but standardization is fundamental for consistency and reliability. Tumor response evaluation criteria have been defined by international groups for application in pharmaceutical clinical trials evaluating new drugs or therapeutic strategies. RECIST 1.1 criteria are exclusively based on unidimensional lesion measurements; changes in tumor size are used as surrogate imaging biomarkers to correlate with patient outcomes. However, increased tumor size does not always reflect tumor progression. The introduction of immunotherapy has led to the development of new criteria (iRECIST, Level of Evidence (LoE) Ib) that consider the possibility that an increase in disease burden is secondary to the immune response instead of progression, with the new concept of Unconfirmed Progressive Disease (a first progression event which must be confirmed on follow-up). Specific criteria were devised for HCC (mRECIST, LoE IV), which measure only enhancing HCC portions to account for changes after local therapy. For GIST treated with imatinib, criteria were developed to account for the possible increase in size reflecting a response rather than a progression by assessing both tumor size and density on CT (Choi, LoE II). This article provides concise and relevant practice recommendations aimed at general radiologists to help choose and apply the most appropriate criteria for assessing response to treatment in different oncologic scenarios. Though these criteria were developed for clinical trials, they may be applied in clinical practice as a guide for day-to-day interpretation. KEY POINTS: Response evaluation criteria, designed for use in clinical trials, might serve as a surrogate biomarker for overall survival. RECIST 1.1 defines measurable and non-measurable disease among which target lesions and non-target lesions are selected at baseline as reference for follow-ups. Some therapies and/or cancers require the use of different criteria, such as iRECIST, mRECIST, and Choi criteria.

Establishing Excellence In ASCVD Clinical Trials Using CCTA Imaging-based Endpoints: Considerations For Global Multi-Center Pharmaceutical Clinical Trials

Establishing Excellence In ASCVD Clinical Trials Using CCTA Imaging-based Endpoints: Considerations For Global Multi-Center Pharmaceutical Clinical Trials

Psychometric evaluation of the patient-reported experience of cognitive impairment in schizophrenia (PRECIS) scale

BackgroundCognitive impairment associated with schizophrenia (CIAS) represents a distinct, persistent, and core group of schizophrenia symptoms. Cognitive symptoms have been shown to have an impact on quality of life. There are several published CIAS measures, but none based on direct patient self-report. It is important to capture the patient’s perspective to supplement performancebased outcome measures of cognition to provide a complete picture of the patient’s experience. This paper describes additional validation work on the Patient-Reported Experience of Cognitive Impairment in Schizophrenia (PRECIS) instrument.MethodsData from two large, international, pharmaceutical clinical trials in medically and psychiatrically stable English-speaking patients with schizophrenia and 88 healthy controls were analyzed. An exploratory factor analysis (EFA) was conducted in one trial (n = 215), using the original 35-item PRECIS. The factor structure suggested by EFA was further evaluated using item response theory (IRT; Samejima’s graded response model), and tested using confirmatory factor analysis (CFA). Both EFA and CFA results were tested in a second trial with similar inclusion/exclusion characteristics (n = 410). Additional statistical properties were evaluated in healthy controls.ResultsEFA suggested that the best solution after item reduction suggested a factor structure of 6 factors based on 26 items (memory, communication, self-control, executive function, attention, sharpness of thought), supporting a total score, with an additional 2-item bother score (28 items in all). IRT analysis indicated the items were well-ordered within each domain. The CFA demonstrated excellent model fit, accounting for 69% of the variance. The statistical properties of the 28-item version of the PRECIS were confirmed in the second trial. Evidence for internal consistency and test-retest reliability was robust. Known-groups validity was supported by comparison of healthy controls with patients with schizophrenia. Correlations indicated moderate associations between PRECIS and functioning instruments like the Schizophrenia Cognition Rating Scale (SCoRS), but weak correlations with performance-based outcomes like MATRICS Consensus Cognitive Battery (MCCB).DiscussionUsing two clinical trial samples, we identified a robust factor structure for the PRECIS and were able to replicate it in the second sample. Evaluation of the meaningful score difference (MSD) should be repeated in future studies, as these samples did not show enough change for it to be evaluated.ConclusionsThis analysis provides strong evidence for the reliability and validity of the PRECIS, a 28-item, patient-reported instrument to assess cognitive impairment associated with schizophrenia. The correlation with functioning and the weak correlation with performance on cognitive tasks suggests that patient reports of cognitive impairment measure a unique aspect of patient experience.

Phytochemicals as potential active principal components for formulation of alternative antifungal remedies against Trichophyton spp.: a systematic review

Abstract In this age of emergent resistance to antimicrobial agents, pathogenic fungi are not an exception. Diverse strategies have been implemented to curb rampant fungal infections including screening new drugs and stewardship programs. A plethora of recent studies have proved that phytochemicals are efficacious against pathogenic fungi and have potent antifungal activity. This review examines the use of phytochemicals as possible alternative antifungal agents against dermatophytes particularly Trichophyton spp. Literature search was done using three search engines namely Google Scholar, PubMed and Science Direct limited to the year 2019–2023 only. A total of 30 articles were included and 48 plant extracts were evaluated. The major phytochemicals that proved to be potent antifungals both in vitro and in vivo were terpenoids and phenolics. The antifungal potential of phyto-compounds was significantly elevated by incarnation with nanotechnology. Although much has been done in screening of herbal extracts as possible antifungal agents huge gaps still exist on full characterization of all active herbal extracts with antifungal potential especially against resistant strains, together with their mechanism of action, formulation of pharmaceutical dosage forms and clinical trials.

Patterns of breast cancer trial enrollment in a prospective patient database at a comprehensive cancer center.

e23026 Background: Clinical trials (CTs) play a crucial role in expanding the landscape of breast cancer (BC) treatment, improving patient’s (pts) outcome and quality of life. Success of CTs relies heavily on pt recruitment. Understanding barriers for CT non-enrollment (NE) despite opportunities to enroll in real world diverse populations can provide valuable insight into barriers to and facilitators of CT participation. Methods: Coordinators registered pts offered BC trial opportunities at the O’Neal Comprehensive Cancer Center at UAB (University of Alabama at Birmingham) from 12/2020 to 12/2023. Identifiers, ethnicity, race, NE reasons and dates (referral, consent, enrollment, and NE) were recorded. CTs were grouped as Pharmaceutical versus Academic based on sponsorship. Descriptive analysis, Fisher’s exact and Mann Whitney U were calculated using Python. Results: A total of 559 pts were offered a CT with a median age of 55 years. There were 145 pts (27%) enrolled (Gp1), 65 (12%) signed consent with NE (Gp2), and 334 (61%) were NE prior to signed consent (Gp3). Most common NE reason in Gp2 and Gp3 was not meeting protocol eligibility (66% & 43%). Gp3 NE reasons included lack of interest or confidence, insurance and logistics, concern over adverse events, delayed therapy start and change to Standard of Care. In terms of ethnicity and race, most pts were Non-Hispanic White (NHW 312, 56%) followed by Black (NHB 165, 30%). Gp1, Gp2 and Gp3 were 28% vs 15%, 59% vs 56%, 11% vs 15% respectively. NHW pts had higher enrollment to CTs compared to NHB (OR 1.135, p 0.73). For Gp2 and Gp3, patterns of NE were similar among NHW and NHB pts such as lack of interest or confidence (11% in Gp3). In Gp2, More NHB pts had NE due to not meeting protocol eligibility (58% vs 75%). In Gp3, NHW pts had higher NE due to insurance and logistics (8% vs 4%). Median Gp1 consent to enrollment and Gp2 consent to NE were 14 and 11 days. Academic CTs (467, 84%), when compared to Pharmaceutical CTs (92, 16%), had higher enrollment (Gp1 28% vs 16%. OR 2.07, p 0.01). NE reasons did not change significantly between CT types in Gp2 and Gp3. Pharmaceutical CTs had longer median time from referral to enrollment (27 vs 13 days, p 0.001). Of those who signed consent (Gp1 and Gp2), enrollment rate was 69%, with more NHW than NHB pts participating (73% vs 63%, OR 1.56, p 0.19) and more participation to Academic than Pharmaceutical CTs (71% vs 58%, OR 1.77, p 0.18). Conclusions: UAB exceeded the national average of BC CT enrollment (27% vs 9%). Only 50% of NE was related to not meeting protocol eligibility criteria. Issues such as lack of confidence in CTs, concern over adverse events, delayed therapy start date and logistics remain active barriers. NHW and NHB pts had similar enrollment rates, consistent with prior data. NHB pts had higher protocol ineligibility due to more Denovo Stage 4 diagnoses. Academic CTs had better enrollment rate and shorter time to enrollment. Further studies are needed to overcome barriers to enrollment on clinical trials.

A new model to enhance enrollment of diverse participants to therapeutic clinical trials.

TPS1640 Background: Disparities in United States clinical trial participation are well described, with the inclusion of only 8% Black, 6% Asian, and 1% Hispanic participants in phase III oncology trials supporting US FDA filings in 2020. The FDA, Cancer Moonshot, and ASCO-ACCC have issued guidance, sponsored initiatives, and developed strategies to raise awareness around the importance of equality, diversity, and inclusion at centers with current clinical research capabilities. Centers with ongoing research capability are typically large academic or private practice sites located in urban areas. There is an urgent need to expand clinical trial offerings to rural communities as geographic constraints disproportionally limit people of color and people of low socioeconomic status from accessing innovative drugs offered only through clinical trials. An additional contributing factor to low enrollment of diverse participants is a lack of racial, ethnic, gender, and geographic diversity amongst clinical trial investigators, who may be more relatable and, thus, effective at recruiting underrepresented patients to clinical trials. Lastly, to provide high quality care for their patients, clinical investigators must have ability to identify and select trials which address the specific needs of the patients within their practice. We hypothesize that a tool which improves identification and inclusion of an expanded investigator pool will result in improved diversity of clinical trial participation. Methods: We have developed a bi-directional matching software program that allows healthcare providers to define their areas of interest and match them to available pharmaceutical company clinical trial opportunities. The software, Golgi-CONNECT, will be piloted with up to 500 oncology-focused healthcare providers across a diverse geographic landscape and up to 6 pharmaceutical companies of varying sizes to evaluate the functionality and usability of the application. Additionally, HCP-reported barriers to clinical trial conduct, inclusive of financial, infrastructure, training, mentoring and lack of support staff will be collected.

Toward Patient Centricity: Why Do Patients With Inflammatory Bowel Disease Participate in Pharmaceutical Clinical Trials? A Mixed-Methods Exploration of Study Participants.

A better understanding of motivations to participate as well as recommendations to reduce barriers to enrollment may assist in design of future clinical trials. We developed a 32-item electronic questionnaire to explore motivations, experiences, and recommendations of inflammatory bowel disease patients, who had participated in pharmaceutical clinical trials in a tertiary center in Canada over the last decade. We employed a mixed-methods approach that integrates both quantitative and qualitative research methods. We distributed a total of 69 e-mails with surveys and received 46 responses (66.6% response rate). Study participants were mostly male (27/46, 58.7%), non-Hispanic White (43/46, 93.5%), with a mean age of 45.5 years (SD 10.9). Most decided to participate in a clinical trial to benefit future patients (29/46, 63.0%). Half of the participants (23/46, 50.0%) reported they were worried about the possibility of receiving placebo, although the majority (29/46, 63.0%) understood they could improve on placebo. The most challenging aspect reported was the number and length of questionnaires (15/46, 32.6%), as well as the number of colonoscopies (14/46, 30.4%). Strategies recommended to increase enrollment were reduction of the chance of receiving placebo (20/46, 43.5%), facilitating inclusion of patients who have failed multiple therapies (20/46, 43.5%), allowing virtual visits (18/46, 39.1%), including subtypes of disease traditionally excluded from trials (16/46, 34.8%) and improving outreach to underrepresented populations (13/46, 28.3%). The vast majority (37/46, 80.4%) reported their experience of participation to be better than expected. These results should help inform the design of future clinical trials with a focus on patient-centricity.

P952 Why do patients with Inflammatory Bowel Disease Take Part in Pharmaceutical Clinical Trials? A qualitative study of Clinical Trial Participants

Abstract Background Recruitment rates to clinical trials in inflammatory bowel disease (IBD) continue to decline. A better understanding of motivations to participate as well as recommendations to reduce barriers to enrolment from a patient perspective may assist in design of future clinical trials. Methods We developed a 32-item electronic questionnaire to explore motivations, experiences and recommendations of patients with IBD, who have participated in pharmaceutical clinical trials in a tertiary centre in Canada. Results We distributed a total of 82 emails with surveys based on the patient details available to the study team. Using the DillMan Total Design Survey method, participants were followed up one week after the initial email with a reminder phone-call and we received 46 responses (56.1% response rate). Participants were mostly, male (58.7%), non-Hispanic white (93.5%), with a mean age of 45.5 years (SD 10.9). Most participants decided to participate in a clinical trial to benefit future patients with IBD (63.0%). Self-reported knowledge of the possibility of being assigned to placebo on a scale from 0 (no knowledge) to 100 (extremely knowledgeable) was a median of 100 (IQR 100-100) (Table 1). Half of participants (50.0%) reported they were worried about the possibility of receiving placebo, although the majority (63.0%) understood they could improve on placebo. The most challenging aspect reported was the number and length of questionnaires (32.6%), as well of the number of colonoscopies (30.4%). Strategies to increase enrolment recommended by participants were reduction in the chance of receiving placebo (43.5%), facilitating inclusion of patients who have failed multiple therapies (43.5%), allowing virtual visits (39.1%), including subtypes of disease that have traditionally been excluded in clinical trials (e.g., ostomies, fistula) (34.8%), and improving outreach to underrepresented populations (28.3%) (Figure 1). The vast majority (80.4%) reported their experience of participation to be better than expected and would recommend taking part in a clinical trial to other patients with IBD (97.8%). Conclusion Patients with IBD who took part in pharmaceutical trials reported a high level of satisfaction overall. The top three recommendations from patients to improve clinical trial design were reducing the chance of receiving placebo, allowing inclusion of patients who have failed multiple therapies and allowing for virtual visits to reduce travel burden to the clinical trial site. These results should help inform the design of patient centric clinical trials in IBD.

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.

DJS-4 Utilization of clinical research data other than conventional clinical trials for pharmaceuticals and medical devices

DJS-4 Utilization of clinical research data other than conventional clinical trials for pharmaceuticals and medical devices

Center-level self-study identifies opportunities to advance equity in cystic fibrosis clinical trial participation

Clinical trials are a necessary tool for evaluating the effectiveness of newly developed treatments and interventions for cystic fibrosis (CF). Prior work demonstrated a proportional underrepresentation of people with CF (pwCF) identifying as part of a minoritized racial or ethnic group in clinical trials. In order to establish a baseline for improvement efforts, we undertook a center-level self-study to evaluate if the racial and ethnic backgrounds of pwCF participating in clinical trials at our CF Center in New York City reflect our overall patient diversity (N = 200; 55 pwCF identifying as part of a minoritized racial or ethnic group and 145 pwCF identifying as non-Hispanic White). A smaller proportion of pwCF identifying as part of a minoritized racial or ethnic group participated in a clinical trial as compared to pwCF identifying as non-Hispanic White (21.8% vs. 35.9%, P = 0.06). A similar trend was present for pharmaceutical clinical trials (9.1% vs. 16.6%, P = 0.3). When limiting the study population to the pwCF most likely to be eligible for a CF pharmaceutical clinical trial, a larger proportion of pwCF identifying as part of a minoritized racial or ethnic group participated in a pharmaceutical clinical trial as compared to pwCF identifying as non-Hispanic White (36.4% vs. 19.6%, P = 0.2). No pwCF identifying as part of a minoritized racial or ethnic group participated in an offsite clinical trial. Efforts to improve the racial and ethnic diversity of pwCF in clinical trials, both onsite and offsite, will require a shift in how recruitment opportunities are identified and communicated to pwCF.

Points to consider when developing drugs for dry eye syndrome.

Changes in both the social environment (e.g., the increased use of electronic media) and the atmospheric environment (e.g., air pollution and dust) have contributed to an increasing incidence of eye disease and an increased need for eye care. Notably, the signs and symptoms of dry eye syndrome can impact the daily quality of life for various age groups, including the elderly, and usually requires active treatment. The symptoms of dry eye syndrome include tear film instability, hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities. As treatments for dry eye are being developed, a standardized guideline is needed to increase the efficiency of drug development and improve the quality of clinical trial data. In this paper, we present general considerations for the pharmaceutical industry and clinical trial investigators designing clinical trials focused on the development of drugs to treat dry eye syndrome.

Therapeutic education for empowerment and engagement in patients with Parkinson's disease: A non-pharmacological, interventional, multicentric, randomized controlled trial.

In 1997 the European Parkinson's Disease Associations launched the Charter for People with Parkinson's disease that stated the right of patients to be informed and trained on the disease, its course, and treatments available. To date, few data analyzed the effectiveness of education program on motor and non-motor symptoms of PD. The aim of this study was to evaluate the efficacy of an education program as it was a pharmacological treatment, thus choosing as the primary endpoint the change in daily OFF hours, the most widely used outcome in pharmaceutical clinical trials on PD patients with motor fluctuations. Secondary outcomes were change in motor and non-motor symptoms, quality of life and social functioning. The long-term efficacy of the education therapy was also evaluated by analyzing data collected at 12- and 24-weeks follow-up outpatient visits. One hundred and twenty advanced patients and their caregivers were assigned to the intervention or control group in a single-blind, multicentric, prospective, randomized study evaluating an education program structured in individual and group sessions over a 6-weeks period.At the end of study, the intervention group showed a significant reduction in daily OFF hours compared to control patients (-1.07 ± 0.78 vs. 0.09 ± 0.35, p < 0.0001) and a significant improvement was also reported in most secondary outcomes. Patients retained significant medication adherence and daily OFF hours reduction at 12- and 24-weeks follow-up. The results obtained demonstrated that education programs may translate in a notable improvement in motor fluctuations and non-motor symptoms in advanced PD patients.Clinical Trial Registration:Clinicaltrials.gov, identifier NCT04378127.

P242 Universal exclusion of patients with Permanent Ileostomy in Crohn’s disease clinical trials: A systematic review

Abstract Background Crohn’s disease (CD) can be progressive leading to complications such as strictures and fistula requiring surgery in up to 50% of patients within 10 years of diagnosis and increased risk of permanent ileostomy (PI) formation. Approximately one third of patients with PI experience clinical recurrence within the small bowel which may need medical therapy and 16% significant recurrence requiring further surgery. Despite the physical and psychological morbidity associated with PI formation, there is a paucity of research in patients with CD and PI. We performed a systematic review to investigate whether patients with CD and PI were eligible to take part in pharmaceutical clinical trials. Methods MEDLINE, Embase, and the Cochrane library (CENTRAL) databases were searched from inception to April 2022 for randomized, placebo-controlled induction and maintenance trials of biologics and small molecules in adult patients with active CD. Eligibility criteria of included studies were screened by two authors independently. The primary outcome was to determine the proportion of trials that included patients with CD and a PI. Trial characteristics such as number of participants, mean age, sex, trial phase, class of drug, inclusion, or exclusion of patients with ostomy were collected. Results After excluding duplicates 11693 records from databases and additional sources were selected for screening. In total,144 records were assessed for full text assessment and 81 studies (induction: 58 and maintenance: 23) which enrolled 22000 participants were considered eligible (Table 1). The majority were phase 2 trials (n=41, 50.6%), 86.4% (n=70) evaluated efficacy and safety of biologics and the remaining studies (n=11, 13.6%) evaluated oral small molecules. Amongst the induction trials, 39 (67.2%) specifically stated that they excluded patients with an ostomy and the remaining studies (n=19, 32.8%) did not comment. For maintenance trials, 16 (69.6%) stated that they excluded patients with an ostomy and the remaining seven (30.4%) studies did not comment. Twenty-one induction studies and thirteen maintenance studies reported the proportion of patients with prior intestinal resection which ranged from 2.4% to 51%. No clinical trial included patients with a PI. Conclusion Patients with CD and PI have been excluded from pharmaceutical trials of biologics and small molecules to date. This group represents a high-risk patient population that have developed penetrating disease and may require medical therapy to prevent and treat recurrence. There is an urgent need to identify barriers to enrolment and develop eligibility and outcome measures that enable inclusion of patients with CD and PI into clinical trials.

Baloxavir safety and clinical and virologic outcomes in influenza virus-infected pediatric patients by age group: age-based pooled analysis of two pediatric studies conducted in Japan

BackgroundAnti-influenza treatment is important for children and is recommended in many countries. This study assessed safety, clinical, and virologic outcomes of baloxavir marboxil (baloxavir) treatment in children based on age and influenza virus type/subtype.MethodsThis was a post hoc pooled analysis of two open-label non-controlled studies of a single weight-based oral dose of baloxavir (day 1) in influenza virus-infected Japanese patients aged < 6 years (n = 56) and ≥ 6 to < 12 years (n = 81). Safety, time to illness alleviation (TTIA), time to resolution of fever (TTRF), recurrence of influenza illness symptoms and fever (after day 4), virus titer, and outcomes by polymerase acidic protein variants at position I38 (PA/I38X) were evaluated.ResultsAdverse events were reported in 39.0 and 39.5% of patients < 6 years and ≥ 6 to < 12 years, respectively. Median (95% confidence interval) TTIA was 43.2 (36.3–68.4) and 45.4 (38.9–61.0) hours, and TTRF was 32.2 (26.8–37.8) and 20.7 (19.2–23.8) hours, for patients < 6 years and ≥ 6 to < 12 years, respectively. Symptom and fever recurrence was more common in patients < 6 years with influenza B (54.5 and 50.0%, respectively) compared with older patients (0 and 25.0%, respectively). Virus titers declined (day 2) for both age groups. Transient virus titer increase and PA/I38X-variants were more common for patients < 6 years.ConclusionsThe safety and effectiveness of single-dose baloxavir were observed in children across all age groups and influenza virus types. Higher rates of fever recurrence and transient virus titer increase were observed in children < 6 years.Trial registrationJapan Pharmaceutical Information Center Clinical Trials Information JapicCTI-163,417 (registered 02 November 2016) and JapicCTI-173,811 (registered 15 December 2017).

Tinnitus patients encouraged to participate in pharmaceutical clinical trials

Validated test tools are necessary to help those who suffer with tinnitus.