Clinical Research Consulting

ABSTRACTHistorically, clonal hematopoiesis (CH) has been recognized as a confounder of cell‐free DNA (cfDNA) testing. Recent evidence now demonstrates the role of CH as a risk factor in health, generating distinct sources of cfDNA that can be leveraged for liquid biopsy diagnostics. Nonetheless, gaps in standardization challenge the advancement of such diagnostics from development to regulatory approval, through clinical trials, and ultimately, to routine implementation. In 2024, the Blood Profiling Atlas in Cancer (BLOODPAC) Consortium, a collaborative infrastructure for developing standards and best practices for liquid biopsy assays, established the CH/clonal hematopoiesis of indeterminate potential (CHIP) Working Group to address the need for accurate identification and removal of CH from liquid biopsy results. As a first step to support the interpretability of CH/CHIP results, the Working Group developed this lexicon to standardize terms and provide a unified vocabulary related to CH and liquid biopsy, DNA sequencing tests, biomarkers, and clinical use cases, facilitating communication within the field. BLOODPAC's CH/CHIP Working Group believes that terminology agreement across these various stakeholders can improve communication in the field and unify future data collection efforts across studies.

The hepatitis C virus (HCV) is a liver tropic (+)-sense single-stranded RNA virus that chronically infects more than 75 million individuals globally and is one of the major causes of chronic liver disease and liver cancer. Historically, interferon (IFN) was the only therapy for treating and curing HCV, but it was plagued with a significant number of serious side effects and the cure rates were approximately only 40%. Development of direct-acting antivirals targeting key viral nonstructural proteins was undertaken with the objective to eliminate the use of IFN, increase cure rates, reduce the duration of therapy, and minimize side effects. The nucleotide prodrug, sofosbuvir (SOF), was the first liver-targeted DAA identified to act on the NS5B viral polymerase. It exhibited a pan-genotypic character, a high barrier to the development of resistance, and excellent intrinsic potency. Clinical trials demonstrated that SOF was safe and well tolerated, and in combination with other DAAs, it showed exceptional efficacy in curing HCV across a wide patient demographic and all viral genotypes with only 12 weeks of therapy. Sofosbuvir was approved by the US FDA in 2013 and EMEA in 2014 and has been designated an essential medicine by the WHO. Drug combinations with SOF as the backbone have cured millions of individuals globally. An overview of the discovery and development of sofosbuvir is described in this chapter.

Oral malodor negatively impacts a person's quality of life and may affect up to 50% of the population. The aim of this randomized, placebo and no-product controlled, evaluator-blind, proof-of-concept study was to evaluate the effectiveness and safety of the single use of two experimental lozenges containing the laccase enzyme and green coffee extract (with and without flavor) in reducing intrinsic oral malodor. Following 12-16 h of avoidance of oral hygiene,156 generally healthy subjects presented at screening and baseline visits with a mean organoleptic odor intensity (OI) score of ⩾2 and an OralChromaTMreading of ⩾125 parts per billion (ppb) hydrogen sulfide (H2S) gas and were randomly assigned to receive either one of the two experimental lozenges, a placebo lozenge, or no-product. Following the supervised use of the assigned products, subjects' oral malodor was evaluated using OI assessments and OralChromaTMmeasurement for volatile sulfur compounds (VSCs) immediately following product use (approximately 5 min), and at 30 min, 1 h, 2 h, 3 h and 4 h. The two experimental lozenges, with and without flavor, showed significant reductions in OI scores compared with the placebo and no-product groups at all time points (p< 0.001). At 5 min post-product use, the experimental lozenges, with and without flavor, were significantly better than the no-product group in reducing the VSCs (p< 0.04). The results of individual VSC components (hydrogen sulfide, methyl mercaptan and dimethyl sulfide) were variable; both experimental lozenges notably reduced hydrogen sulfide and methyl mercaptan levels in most post-use assessments. Four minor adverse events were reported, none of which were directly linked to the product. In conclusion, the experimental lozenges, whether flavored or not, were safe and effective in reducing oral malodor over a span of 4 h, based on organoleptic OI scores.Clinical Trial No: NCT05950529.

The field of digital therapeutics (DTx), software programs that prevent, manage, and treat medical conditions, continues to grow. DTx offers new treatment options and has the potential to close gaps in care caused by unmet patient needs, provider shortages, or socioeconomic or geographical disparities. However, the field of DTx has not seen steady adoption owing to barriers, particularly related to coverage, payer acceptance of the category, provider use, and integration within existing health care delivery tools. One challenge for payers to effectively evaluate and cover DTx products is ensuring that consistent data elements are listed for these products in traditional drug compendia databases. Managed care organizations will need similar information about DTx product features as are available for traditional medications to inform coverage and reimbursement decisions. The Academy of Managed Care Pharmacy DTx Advisory Group developed and distributed a request for information to the 5 top drug compendia companies to assess how compendia products incorporate DTx and prescription DTx. This article summarizes how DTx are listed within different compendia products and offers insights on future data needs to adequately inform payers. As the DTx sector grows and consumer demand rises, compendia listing services will need to evolve to accommodate these new therapies and treatment modalities and facilitate patient access and efficient claims processing. Recommendations for how compendia companies can support managed care in these efforts are outlined.

Suboptimal awareness and low rates of hepatitis delta virus (HDV) testing contribute to underdiagnosis and gaps in accurate estimates of U.S. HDV prevalence. We aim to provide an updated assessment of HDV prevalence in the U.S. using a comprehensive literature review and meta-analysis approach. A comprehensive literature review of articles reporting HBsAg seroprevalence and anti-HDV prevalence was conducted to calculate country-specific rates and pooled prevalence of CHB and HDV using meta-analyses. Country-specific CHB and HDV rate estimates were combined with number of foreign-born (FB) persons in the U.S. in 2022 from U.S. Census Bureau to estimate total numbers of FB with CHB and HDV, respectively. These estimates were further combined with updated estimates of U.S.-born persons with CHB and HDV to yield the total number of persons with CHB and HDV. In 2022, we estimated 1.971 million (M) (95% CI 1.547-2.508) persons with CHB; 1.547 M (95% CI 1.264-1.831) were FB and 0.424 M (95% CI: 0.282-0.678) were U.S.-born. The weighted average HDV prevalence among FB persons in the U.S. was 4.20% (64 938 [95% CI 33055-97 392] persons), among whom 45% emigrated from Asia, 25% from Africa, and 14% from Europe. When combined with updated estimates of U.S.-born persons with HDV, we estimate 75 005 (95% CI: 42187-108 393) persons with HDV in the U.S. Including both FB and U.S.-born persons, we estimated that 1.971 M and 75 005 persons were living with CHB and HDV, respectively, in the U.S. in 2022.

Although paternal incest has been well documented and studied, there is very little research on maternal incest, and victims rarely seek help. New clinical evidence suggests that maternal incest occurs at a much higher rate than previously thought. Estimates indicate approximately 5% of sexually abused girls and 20% of sexually abused boys have been victimized by women perpetrators. Myths that discourage the acceptance of male victimization are compounded by the idea of mothers as caregivers and nurturers. The societal taboo surrounding maternal incest can be particularly damaging to victims, resulting in guilt and shame. The attitudes of mental health professionals in regard to myths about maternal incest can promote conditions that either encourage or discourage men or boys from opening up about this type of abuse. This article reviews the prevalence and dynamics of maternal incest, the shame felt by victims and its consequences, treatment approaches, and areas of future research needed.