Clinical Trial Operations

Invited commentary

Pharmacists a valuable resource for patients with Alzheimer disease and their caregivers

Having diverse participants in clinical trials ensures new drug products work well across different demographic groups, making health care safer and more effective for everyone. Information on the extent of Native Hawaiian and Pacific Islander participation in clinical trials is limited. To examine representation of Native Hawaiian and Pacific Islanders in clinical trials leading to the first US Food and Drug Administration (FDA) approvals for the 10 drug products with the top worldwide sales forecasts in 2024. Cross-sectional secondary analysis of existing data from clinical trials that took place from 2006 to 2021 in the US. All clinical trials that were included in the FDA first approval application for the 10 drug products were evaluated in this study. Data were analyzed from February to August 2024. Participation in a clinical drug trial. Comparison of the proportion of Native Hawaiian and Pacific Islander participation in clinical trials for the 10 drug products with top sales forecasts in 2024 to the Native Hawaiian and Pacific Islander population proportion. In this cross-sectional study of 139 062 individuals, Native Hawaiian and Pacific Islander participation in clinical trials for the 10 drug products with top sales forecasts was either unknown or low. For 6 of the 10 drug products (60%), the number of Native Hawaiian and Pacific Islander participants was not documented. All trials that reported Native Hawaiian and Pacific Islander participation had fewer Native Hawaiian and Pacific Islander participants than would be expected based on their US population proportion, with 2 of the differences being statistically significant. Of the trials that disaggregated Native Hawaiian and Pacific Islander participants from other racial groups, the number of Native Hawaiian and Pacific Islander participants was 8 for risankizumab-rzaa (0.38% of participants vs 0.49% of the population; percentage point difference, -0.11%; 95% CI, -0.37% to -0.15%), 7 for bictegravir/emtricitabine/tenofovir alafenamide (0.38% of participants vs 0.49% of the population; percentage point difference, -0.10%; 95% CI, -0.39% to 0.18%), 27 for 4vHPV/9vHPV (0.15% of participants vs 0.46% of the population; percentage point difference, -0.31%; 95% CI, -0.37% to -0.26%), and 90 for BNT162B2 COVID-19 vaccine (0.20% of participants vs 0.52% of the population; percentage point difference, -0.32; 95% CI, -0.36% to -0.27%). In this cross-sectional study, limited documentation and participation of Native Hawaiian and Pacific Islander individuals in clinical trials for drug products with top sales forecasts was found. This is especially concerning because Native Hawaiian and Pacific Islander individuals have a higher risk than other racial groups for type 2 diabetes, cancer, and several other conditions the products examined in this study treat. Given the importance of enrolling Native Hawaiian and Pacific Islander participants in clinical trials, sites should be established in key geographic regions, such as Hawai'i, and postmarket studies should be conducted within Native Hawaiian and Pacific Islander populations.

Under Reporting of Patient Reported Outcomes (PROs) in Myeloproliferative Neoplasm (MPN) Clinical Trials

Prospective Clinical Trial Registration: A Prerequisite for Publishing Your Results.

2444 Development of an instrument to identify factors influencing point of care recruitment in primary care settings: A pilot study at University of Utah Health

To examine a complete population of clinic attenders in order to compare the demographics of patients who participated in a clinical study with those who had not. These were subdivided into trials of antivirals, trials for drugs used in opportunistic infections or symptomatic HIV and epidemiological studies. The setting was an established London teaching hospital. All patients diagnosed HIV-positive and attending between July 1983 and 1 January 1999 with one measured CD4 count and at least one follow-up visit were included. The demographics of those participating in a clinical study were compared to those not enrolling using chi2 tests and Wilcoxon tests. Cox models were used to determine factors related to participation in clinical studies. Data from 2703 patients representing 5342.7 person-years' follow-up were assessed. Median time of follow-up was 23.6 months. Six hundred and eighty-seven (33%) patients had ever participated in a clinical study. After adjustment for demographic factors in multivariate analysis using Cox models, homosexuals were more likely to participate compared with heterosexuals or injecting drug users (IDU) (P = 0.0035 and P = 0.0001, respectively). Women were more likely to enter a study (P = 0.02) and there was no difference between Caucasians and black Africans (P = 0.35). Between the three types of studies few differences were seen. High rates of participation in clinical trials and epidemiological studies were seen in this cohort. In keeping with other studies, homosexual men were well represented but IDU were under-represented. However, women and black African patients showed good uptake of all clinical studies. Hence in this population there is some success in targeting representative groups to participate in clinical studies, but more effort needs to be made with IDU.

The Need for Large Clinical Studies in Perioperative Medicine

Clinical trials offer access to advanced treatments, yet only 2-10% of cancer patients participate. Many factors contribute to patient participation, including patient social determinants of health (SDOH) such as age, rurality, race, education, and socioeconomic status. The purpose of this study is to determine if SDOH measures are related to clinical trial participation in a community cancer center in the great plains. A retrospective study was conducted by evaluating all patients treated for malignancy in the oncology electronic health record (EHR) between 2018 and 2022. Demographic information was also obtained from the EHR. U.S. Census Bureau data was used to define location as urban or rural. Documentation available of formal consideration for clinical treatment trial screening came from cancer research departmental data. During the study period, 15,514 patients were treated for malignancy (WCP). Of those, 1,311 had documentation available showing formal consideration for clinical treatment trial screening (SCT group). Urban patients made up 22.5% of the WCP and 32.0% of SCT group. SCT population lived a median distance of 69.9 miles from the study site whereas the median distance from study site for WCP was 89.8 miles. Screened patients had an average age of 67.2 while the average age for all patients was 72.3. SCT group was 94.7% Caucasian and WCP was 93.1% (p = 0.033). 78.1% of WCP spoke English while 79.9% screened did (p = 0.14). The available data from the EHR and ancillary data sources had significant limitations with potential for impacting validity of endpoints. While this data provides areas that are opportunities of focus for potential improvement, additional studies will be needed to further assess the true impact of SDOH in consideration for clinical trial involvement.

Now viewed as its own scientific discipline, clinical trial methodology encompasses the methods required for the protection of participants in a clinical trial and the methods necessary to provide a valid inference about the objective of the trial. Drawing from the authors' courses on the subject as well as the first author's more than 30 years wor

Lithium and antipsychotics are often prescribed to treat bipolar disorder or psychotic disorders in women of childbearing age. Little is known about the consequences of these medications during pregnancy for the developing child. The objective of this article is to systematically review findings from preclinical and clinical studies that have examined the neurodevelopmental consequences of intrauterine exposure to lithium and antipsychotics. A systematic search was performed in Embase, Medline, Web of Science, PsychINFO, Cochrane, and Google Scholar. Clinical and experimental studies were selected if they investigated neurodevelopment of offspring exposed to lithium or antipsychotics during gestation. Quality of clinical and preclinical studies was assessed by the Newcastle–Ottawa Scale and the SYRCLE’s risk of Bias tool, respectively. In total, 73 studies were selected for qualitative synthesis and three studies were selected for quantitative synthesis. Of preclinical studies, 93% found one or more adverse effects of prenatal exposure to antipsychotics or lithium on neurodevelopment or behaviour. Only three clinical cohort studies have investigated the consequences of lithium exposure, all of which reported normal development. In 66% of clinical studies regarding antipsychotic exposure, a transient delay in neurodevelopment was observed. The relative risk for neuromotor deficits after in utero exposure to antipsychotics was estimated to be 1.63 (95% CI 1.22–2.19; I2 = 0%). Preclinical studies suggest long-term adverse neurodevelopmental consequences of intrauterine exposure to either lithium or antipsychotics. However, there is a lack of high-quality clinical studies. Interpretation is difficult, since most studies have compared exposed children with their peers from the unaffected population, which did not allow correction for potential influences regarding genetic predisposition or parental psychiatric illness.

Background. The prevalence of joint diseases affecting cartilage tissue and all components of the joint due to trauma and degenerative-dystrophic conditions has notably risen in recent years. Despite an extensive body of research, addressing large bone and cartilage defects remains a significant clinical challenge. This reality underscores the imperative to innovate treatment methods and enhance existing approaches. In this review, we will examine and analyse contemporary materials and techniques for replacing cartilage defects, including hydrogels, nanofibers, 3D membranes, and BioCartilage. Additionally, it explores key aspects of orthobiology, specifically the utilisation of mesenchymal stem cells and exosomes. The article also considers instances of employing modern methods to replace cartilage defects in both experimental and clinical studies. The purpose was to investigate, analyse, and interpret data on the application of contemporary materials and methods for cartilage defect replacement as described in experimental, clinical, and review studies. Materials and methods. A comprehensive literature search was conducted using terms such as osteochondral defect, BioCartilage, nanofiber, allograft cartilage, mesenchymal stem cell, hydrogel, and nonwoven membranes. The search was conducted on the basis of Google Scholar, CrossRef, PubMed databases for the last 5 years. Logical analysis and evaluation were performed on the results of studies encompassing diverse modern technologies and principles for replacing cartilage tissue defects. Results. Microfracturing and tunneling are quite effective methods in replacing cartilage defects with cartilage-like regenerate. Their effectiveness reduces with increa-sing mechanical and axial loads on the formed regenerate. Experimental studies show that physical properties of hydrogel can be compared to native cartilage tissue. Moreover, hydrogel can be used as a matrix for the delivery of anti-inflammatory and some biological drugs. However, this method needs more specific clinical and experimental studies to be put into practice. The use of exosomes to replace osteochondral defects is a simple method, but rapid degradation limits its effectiveness. Combining exosomes with hydrogel or hyaluronic acid can solve these problems by prolonging their release and degradation, enhancing biological activity and biocompatibility. Bioprinting and nanofiber sponge (3D membrane) have reasonable theoretical and experimental value for replacing cartilage defects and require further clinical studies. Promising methods of cartilage tissue regeneration are the implantation of autologous chondrocytes, the use of ChondroFiller and BioCartilage. For a wider assessment of the results of using these treatment methods, longer clinical studies are needed. ­Conclusions. An analysis of more than 36 literature sources, including review, experimental, and clinical studies, reveals a structured summary of the latest research and developments in cartilage tissue defect repair. There is no universal technology for replacing cartilage defects that would be suitable for all patients. Therefore, this review highlights the advantages of different methods for cartilage defect repair adapted to specific clinical cases. Based on the analysis of literature data regarding the use of implant materials to correct cartilage defects in orthopaedics and traumatology, it can be concluded that the chosen direction of scientific research is relevant and significant. Additionally, certain aspects of the development of this issue can be outlined, and questions requiring further study and resolution can be identified.

Cancer medicine continues to evolve into a more molecularly based discipline with many new treatments being developed aimed at specific cancer-related pathways and genetic alterations. In order to meet the challenges of the evolving science, new clinical trial designs and approaches for treatment trials are needed to evaluate the promise of these potential therapies. The National Cancer Institute (NCI) with the national NCI Clinical Trials Network (NCTN) Groups will launch two clinical research initiatives in lung cancer in 2014 that demonstrate innovative approaches to the design and conduct of clinical trials. The first initiative is the ALCHEMIST trial (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial) which is aimed at patients with lung adenocarcinoma that has been entirely removed by surgery. In this study, samples of tumor tissue from thousands of patients will be tested for two specific genetic alterations, one in the EGFR gene, and the other in the ALK gene. These alterations are not common; about 10% of the lung cancer patient population in the US will have tumors with alterations in the EGFR gene and 5% will have alterations in the ALK gene. Rather than conduct a single trial for each alteration, the screening component of the ALCHEMIST trial will screen patients for both alterations at the same time. The ALCHEMIST is connected to 2 specific NCI-supported NCTN Group clinical treatment trials that are each testing a targeted agent specific for one of the alterations in conjunction with adjuvant therapy. Patients found to have tumors containing one of the alterations will be offered enrollment onto the appropriate clinical treatment trial. Every patient in the ALCHEMIST trial, including those without an EGFR or ALK alteration, will also be studied for cancer risk characteristics and their tumor tissue will be analyzed in a research genomics initiative conducted by the NCI Center for Cancer Genomics (CCG). This effort will employ next-generation sequencing technology to capitalize on the foundation of the CCG's earlier effort, the Cancer Genome Atlas. The second initiative, the Advanced Squamous Cell Carcinoma Lung Master Protocol, is a public-private effort made possible through collaboration with stakeholders including the NCI, NCTN Groups, FDA, NIH Foundation, the Friends of Cancer patient advocacy group, and the pharmaceutical industry. By pooling resources to screen tumor samples from about a thousand patients per year with advanced squamous cell carcinoma for multiple genetic alterations, this master protocol will enable several, randomized, phase II clinical trials with promising new agents to take place in parallel within a single study management framework. Agents will be evaluated rapidly and either be further evaluated in a phase III clinical trial or replaced by other new agents for phase II evaluation, without having to develop individual trials de novo each time. Compared with the usual process of developing clinical trials, these two new design approaches will hopefully allow more patients to be enrolled in trials with agents targeted for important molecular characteristics specific for their tumors and the trials will yield clinically useful results more rapidly. Citation Format: Margaret M. Mooney, Jack Welch, Jeffrey S. Abrams. Clinical trial design and master protocols in NCI clinical treatment trials. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr IA08.

Factors influencing participation of psychiatry inpatients in clinical trials.

<p>Supplementary Methods, Table S1, Figures S1-7. Methods for quantitative multiplex proteomics imaging (QMPI) Clinical studies: Statistical plan Table S1. Clinical Validation Study. Comparison of Predictive Value of the 8-Biomarker Assay for Favorable Pathology with D'Amico Risk Categories. Figure S1. Outline of all four quantitative multiplex immunofluorescence triplex assay formats Figure S2. Clinical validation study, full cohort (N=276): performance for "GS 6" pathology (surgical Gleason =3+3 and localized {less than or equal to}T3a). A) Sensitivity (P[risk score> threshold| "non-GS 6" pathology]) of the assay, as a function of medical decision level. Figure S3. Clinical validation study, full cohort (N=274): performance for prediction of favorable pathology (surgical Gleason {less than or equal to}3+4 and organ-confined {less than or equal to}T2). Figure S4. Clinical validation study, Subset of validation cohort that contained sufficient annotation for National Comprehensive Cancer Network (NCCN) and D'Amico categorization (N=256) Figure S5. Clinical validation study: performance for prediction of favorable pathology. Figure S6. Net Reclassification Index analysis illustrates how biomarker assay categories of favorable (risk score {less than or equal to}0·33) and non-favorable (risk score >0·8) may supplement NCCN Figure S7. Decision Curve Analysis provides another method for characterizing performance of different risk systems and at different cut points.</p>