Recent Updates on the Guidelines to Clinical Trials through Innovations

The CDER Center for Clinical Trials Innovation (C3TI) was recently created by the FDA's Center for Drug Evaluation and Research (CDER) to facilitate and expand novel approaches to clinical trials intended to increase the effectiveness of drug development. Through a consolidated knowledge repository, C3TI would disseminate information and resources on clinical trial innovation subjects through enhanced internal and external communication. Furthermore, to enable certain demonstration projects and test, implement, and scale the integration of innovation into clinical trials. Additionally, C3TI has assigned a single CDER contact to both internal and external stakeholders in order to streamline the coordination of all innovation-related inquiries. In an effort to update the guidelines for conducting clinical trials, the FDA released three guidance documents—two drafts and one final. The expanding use of decentralized clinical trials (DCTs), the increasing potential of clinical trials integrated into routine clinical practice to capitalize on the value of real-world data (RWD), and design considerations for multiregional clinical trials (MRCTs) for oncology drugs are some of the important aspects of the quickly changing clinical trial landscape that are addressed by these policies.[1]

Updates to DCT (Final guidance)

The FDA released its final DCT guidance, Conducting Clinical Trials with Decentralized Elements, in September 2024. It's interesting to note that the title was altered from the May 2023 draft advice, which was titled Decentralized Clinical Trials for Drugs, Biological Products, and Devices.

Local healthcare providers (HCPs) activities in decentralized trials have to be documented in a task log according to the original guidelines. The final guidance, however, does away with this obligation. Rather, it makes clear that local HCPs who are working within their normal area of practice need not to be well-versed on the protocol, investigator's brochure, or investigational substance. Informed permission cannot be obtained by local HCPs while the investigator are main in charge of keeping accurate records. Usually, the investigator or sub-investigator is required to supervise the administration of experimental products. However, local HCPs or remote trial staff may administer medications with well-defined safety profiles and straightforward administration. The safety profile of the product and the recommendations should be used to define the precise strategy. According to the FDA's final guidance on conducting clinical trials with decentralized elements, electronic systems must adhere to 21 C.F.R. Part 11. This implies that the FDA's requirements for electronic records and electronic signatures must be fulfilled by the electronic systems utilized in DCTs. The purpose of these standards is to guarantee the security, dependability, and correctness of electronic records. In order to reduce data variability, the final guidance emphasizes the significance of standardizing trial-related tasks carried out by regional HCPs or other trial staff. Training or video supervision, in addition to specific protocol instructions, can assist reduce this danger. Decentralized components should be explicitly described in the protocol, and study records should include information about telehealth visits, such as dates and staff names. Based on the trial population and investigational product, the appropriateness of telehealth visits should be evaluated, taking patient privacy into account. The guidelines stress that individuals without access to digital health technologies (DHTs) indicated by the protocol must be accommodated. Exclusions based on device ownership should be avoided, and other options, such as sponsor-provided telecommunications services, should be investigated. The safety monitoring strategy must take into account the difficulties of decentralized aspects while also providing clear guidance on participants' support and care options.  The final guidance emphasizes the importance of coordinating decentralized activities and ensuring data quality. Sponsors are responsible for tracking networks, service providers, and their roles, while investigators must oversee data from regional HCPs and other trial staff. For standard clinical tests, local clinical laboratories are often suitable. However, specialized or study-specific tests require designated laboratories. Participants can use various methods (home collection kits, local HCPs, clinical laboratories, or remote staff) to collect specimens, which are then sent to specific laboratories for processing. Investigators must maintain a record of all laboratories involved. [2], [3], [4]

Updates to RWD (In draft)

As moving towards the RWD the FDA's routine Clinical Practice Trials Draft Guidance intends to improve clinical trial efficiency by incorporating them into routine clinical practice. This strategy focuses on gathering critical data, increasing participant convenience, and enrolling more representative populations. While subject to FDA rules, these trials can be done for both authorized and unapproved medications with well-established safety profiles. Sponsors must work with healthcare institutions to clarify roles and provide proper oversight of trial-related activities. A quality by design (QbD) strategy is advised for trial design and risk mitigation, with an emphasis on flexibility and risk-based monitoring.[4]

Updated to MRCT (In draft)

The FDA's Oncology MRCT Draft Guidance provides detailed recommendations for designing and conducting multinational clinical trials in oncology. Recognizing the potential value of MRCTs, the FDA emphasizes the importance of ensuring that trial results are generalizable to the U.S. population. Given concerns about the decreasing proportion of U.S. participants in oncology MRCTs and potential differences in demographic and clinical characteristics, the FDA recommends careful consideration of various factors, including patient-related, disease-related, healthcare system, and socio-cultural factors, to assess the suitability of an MRCT.[4]

Clinical trials are moving towards empowering sites and patients

The need for personalized support for both sites and patients is likely to increase as the clinical trial industry continues to evolve. The lessons learned from rare disease research underscore the importance of considering each trial's unique requirements at the start. These individuals can help to address operational challenges and improve site relationships, patient satisfaction, and overall trial efficiency. Additionally, patient journey coordinators can help patients to manage their work schedules and childcare needs, and to ensure that they can attend appointments easily. By integrating personal touch points with operational efficiency, patient journey coordinators can improve the likelihood of patients staying engaged throughout the trial. [5]

In conclusion, the FDA has been actively attempting to modernize clinical trials, emphasizing efficiency, patient experience, and data quality. The establishment of the C3TI to foster innovation, the publication of guidance documents on decentralized clinical trials (DCTs), routine clinical practice trials (RCTs), and multi-regional clinical trials (MRCTs) in oncology, and the recognition of the importance of personalized support for sites and patients are all key initiatives. These efforts seek to expedite processes, improve patient access, and ensure the accuracy of clinical trial results.

References:

1. James R. Ravitz, FDA Establishes CDER Center for Clinical Trial Innovation (C3TI),McDermott Will & Emery. Accessed on: 2024 01 May 2024; Published on: 02 December, 2024

URL: https://www.mwe.com/insights/fda-establishes-cder-center-for-clinical-trial-innovation-c3ti/

2. Brenda Sandburg, FDA’s Decentralized Trial Guidance: Investigator, Health Care Provider Demarcation Raises Questions, Pink sheet citeline regulatory. Published on: 24 July 2023; Accessed on: 02 December 2024

URL: https://insights.citeline.com/PS148560/FDAs-Decentralized-Trial-Guidance-Investigator-Health-Care-Provider-Demarcation-Raises-Questions/

3. Jessa Boubker, Monica Chmielewski, Kyle Faget, FDA Finalizes Decentralized Clinical Trial Guidance, Applied clinical trials. Published on: 25 November 2024 ; Accessed on: 02 December 2024 URL: https://www.appliedclinicaltrialsonline.com/view/fda-decentralized-clinical-trial-guidance

4. Ropes & gray, Three of a Kind: FDA Guidance Documents Provide Recommendations on Non-Traditional Clinical Trial Designs. Accessed on : September 25, 2024 ; Published on: 02 December, 2024                     

URL: https://www.ropesgray.com/en/insights/alerts/2024/09/three-of-a-kind-fda-guidance-documents-provide-recommendations-on-non-traditional#:~:text=On%20September%2016%2D17%2C%202024,to%20modernize%20its%20policies%20for

5. Samantha Morley; Danielle Shadforth; and Nishma Patel, Empowering Sites and Patients: The Impact of Personalized Support in Clinical Trials, Applied clinical trials. Published on: 26 November 2024 ; Accessed on: 02 December 2024

URL: https://www.appliedclinicaltrialsonline.com/view/personalized-support-clinical-trials?utm_source=www.appliedclinicaltrialsonline.com&utm_medium=relatedContent

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About the author 

Shruti Talashi

boasts a dual mastery of lab research and writing. Her doctoral study outcome as M.Phil in biomedical science while studying breast cancer and an extraordinary masters degrees dissertation work on exploring role of Gal-lectin in cancer metastasis fuels her extensive research interests. She has gained few publication in journals. Bridging the science-public gap is her passion, aided by expertise in diverse techniques. From oncology to antibiotic/drugs production, she's led and managed complex projects, even clinical trials. Now, as a freelance Content Coordinator for Sinoexpo Pharmasource.com, her industry knowledge shines through valuable insights on cutting-edge topics like GMP, QbD, and biofoundry.