A Small-Molecule Pan-Id Antagonist Inhibits Pathologic Ocular Neovascularization.

Id helix-loop-helix (HLH) proteins (Id1-4) bind E protein bHLH transcription factors, preventing them from forming active transcription complexes that drive changes in cell states. Id proteins are primarily expressed during development to inhibit differentiation, but they become re-expressed in adult tissues in diseases of the vasculature and cancer. We show that the genetic loss of Id1/Id3 reduces ocular neovascularization in mouse models of wet age-related macular degeneration (AMD) and retinopathy of prematurity (ROP). An in silico screen identifies AGX51, a small-molecule Id antagonist. AGX51 inhibits the Id1-E47 interaction, leading to ubiquitin-mediated degradation of Ids, cell growth arrest, and reduced viability. AGX51 is well-tolerated in mice and phenocopies the genetic loss of Id expression in AMD and ROP models by inhibiting retinal neovascularization. Thus, AGX51 is a first-in-class compound that antagonizes an interaction formerly considered undruggable and that may have utility in the management of multiple diseases.

Informed consent process: A step further towards making it meaningful!

Informed consent process is the cornerstone of ethics in clinical research. Obtaining informed consent from patients participating in clinical research is an important legal and ethical imperative for clinical trial researchers. Although informed consent is an important process in clinical research, its effectiveness and validity are always a concern. Issues related to understanding, comprehension, competence, and voluntariness of clinical trial participants may adversely affect the informed consent process. Communication of highly technical, complex, and specialized clinical trial information to participants with limited literacy, diverse sociocultural background, diminished autonomy, and debilitating diseases is a difficult task for clinical researchers. It is therefore essential to investigate and adopt innovative communication strategies to enhance understanding of clinical trial information among participants. This review article visits the challenges that affect the informed consent process and explores various innovative strategies to enhance the consent process.

Challenges in recruitment and retention of clinical trial subjects.

BACKGROUND: Successful recruitment of patients is known to be one of the most challenging aspects in conduct of randomized controlled trials. Inadequate patient retention during conduct of trial affects conclusive results. OBJECTIVE: To assess the level of challenges faced by Indian investigators in recruitment and retention of trial subjects. METHODS: We developed a survey questionnaire on challenges encountered by investigators in subject recruitment and retention which was hosted on a web portal. RESULTS: Seventy-three investigators from India participated in the survey. The frequently encountered challenges in subject recruitment were complexity of study protocol (38%), lack of awareness about clinical trials in patients (37%), and sociocultural issues related to trial participation (37%). About 63% of participants strongly agreed that creating a positive awareness about clinical trials among people through press and media, having a dedicated clinical research coordinator for trial (50.7%), and designing a recruitment strategy prior to study initiation (46.6%) would enhance recruitment. Almost 50.7% of participants agreed that interacting with medical community in vicinity of the study site and educating patients about clinical trials during routine outpatient department visits (46.6%) would enhance recruitment. Experiencing a serious adverse event, subject's fear for study procedures (47%) and side effects (44%) were thought to have a moderate effect on subject retention. CONCLUSION: Our survey has put forth factors related to negative publicity by media, lack of patient education about clinical trials; complex study designs are barriers to clinical trial recruitment in India. It is essential to devise innovative and effective strategies focusing on education of public and mass media about clinical research in India.

Opinions and perceptions regarding the impact of new regulatory guidelines: A survey in Indian Clinical Trial Investigators.

BACKGROUND: Clinical research in India experienced dramatic changes with series of stringent guidelines introduced by regulatory authorities. These guidelines posed significant challenges for the clinical trial industry. OBJECTIVE: To assess the perceptions and opinion of Indian Investigators about the new regulatory guidelines. METHODS: We developed a survey questionnaire on recent regulatory guidelines which was hosted on a web portal. Seventy-three investigators from India participated in the survey. RESULTS: Central registration of Ethics Committees (ECs) was agreed by 90.1% participants, 76.8% participants agreed to compensation of subjects for study related Serious Adverse Events (SAE's). The compulsion to include government sites in clinical trials was not agreed by 49.3% participants while 21.2% agreed to it. Restriction on a number of trials per investigator was agreed by 49.3% of participants while 40.9% disagreed. Participants (50.7%) disagreed to the introduction of audio-video (AV) recording of informed consent, 36.6% agreed and 12.7% were neutral. DISCUSSION: Participants observed that post central registration; ECs have improved systems with adequate member composition, functional Standard Operating Procedures, and timely approvals. Participants agreed that compensation of study related SAE's would assure subject protection and safety. The introduction of AV consenting was strongly debated sighting sociocultural issues in the implementation of the same. CONCLUSION: Participants endorsed guidelines pertaining to the central registration of ECs, SAE related compensation. Restrictions on a number of trials per investigator and AV consenting were debated ardently. The response of the survey participants who are clinical trial investigators in India showed general acceptance, effectiveness and anticipated compliance to the new regulatory guidelines.

Ethics committees in India: Facing the challenges!

The past few years have seen a tremendous rise in the number of clinical trials conducted in India. This is been attributed to the huge patient population, genetic diversity, and rich technical pool in our country. However, the economical upsurge in the clinical trial industry has also caused concerns pertaining to the efficiency of the Regulatory Agencies and Ethics Committees (EC). The EC plays an important role in the regulation of clinical research at the local level. However, it is seen that many ECs are oblivious to their roles and responsibilities. It is reported that ECs lack standard operating procedures, do not have a proper composition or adequate representation, thus affecting their functions in regulating clinical research. Moreover, ECs seem to function in isolation, as self-sufficient bodies, having no communication with the regulatory agency or other ECs. This brings forth the need for ECs to come together and share their experiences and observations, with the aim of updating themselves and refining their functions. Efforts also need to be focused on capacity building, centralized registration of ECs, and bringing an oversight mechanism in place. The Ethics Committees in India need to work in close association with forums such as the Forum for Ethics Review Committees in India and the Forum for Ethical Review Committees in Asia Pacific, in an effort towards empowering themselves.