Standardization Templates for Regulatory Submissions (ICH, HL7, SPIRIT, TransCelerate, CTFG, WHO ICTRP) PDF

Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI ICH, HL7, SPIRIT, TransCelerate, CTFG, WHO ICTRP By : Prof. Dr. Sweta Kumari Assistant Professor, IGMPI...

Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI ICH, HL7, SPIRIT, TransCelerate, CTFG, WHO ICTRP By : Prof. Dr. Sweta Kumari Assistant Professor, IGMPI For feedback on this lecture please mail on – [email protected] Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/ ICH and ICH M1 Protocol Template  The development of new drugs is a complex process involving clinical trials conducted across multiple countries. This can lead to challenges due to differing regulatory requirements and variations in how clinical trial protocols are formatted. The International Council for Harmonization (ICH) M11 Protocol Template, based on the ICH M11 guideline, aims to address this by establishing a standardized format for clinical trial protocols. This global solution has the potential to streamline the drug development process, making it more efficient and cost-effective. The guidelines include the M11 protocol template and related technical specifications expected to transform how clinical trials are designed and conducted worldwide.  The ICH M11 initiative introduces two crucial deliverables: 1. ICH M11 Clinical Electronic Structured Harmonized Protocol Template (Template): This template provides a standardized structure for clinical trial protocols. It includes required and optional sections, ensuring consistent organization and content across different trials. 2. ICH M11 Technical Specification: This acts as a technical representation of the template, defining the data format for electronic exchange. It facilitates a seamless sharing of protocol information between sponsors, regulatory bodies, and other stakeholders. Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/ Latest Developments on ICH M11 Guidelines  The ICH M11 draft guideline reached step 2 of the ICH process in September 2022. This is a major milestone towards the finalization and implementation globally. The latest improvements in ICH M11 guidelines involve the completion of the M11 protocol template and its technical specifications. These progressions are a result of collaboration between international regulatory authorities, industry experts and other stakeholders. Key highlights include: Comprehensive Coverage: The M11 protocol template incorporates different types of clinical trials, such as interventional and observational studies across all drug development stages (Phases I-IV). User-friendly: This template was made for users to prepare, review, or compare clinical trial protocols easily. Compliance with Regulatory Requirements: The template complies with the regulatory requirements of the member regions of ICH so that protocols are within acceptable limits as per various regulators’ expectations. Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/ Types of Trials and Phases Covered by the M11 Protocol Template  M11, being such a versatile protocol template can be used in different types of clinical trials that include:  Interventional Trials: these are studies where patients receive some specific interventions as per the research plan or protocol made by the investigators.  Observational Studies: These are trials where researchers monitor and collect data about the participants without giving them specific treatments. Phase I: These are early-stage trials that focus on evaluating the safety,  Drug Development Phases: tolerability, pharmacokinetics and pharmacodynamics of a drug. Phase II: This is an intermediate-stage trial to assess how well a drug works and its side effects. Phase III: Large-scale trials that confirm the efficacy of the drug, record side effects and compare it with standard or equivalent therapies. Phase IV: Post-marketing surveillance studies/clinical investigations designed to gather additional information on safety, efficacy, dose (including dosing regimens), treatment duration (long- or short-term), optimal use, etc., as well as any other conditions of use stipulated in product Faculty oflabeling. Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/  Technical Specification: Facilitating Electronic Exchange  A critical component of the ICH M11 guidelines is the technical specification, which serves as a technical representation of the protocol template. This is a specification that was designed to make it possible to exchange protocols electronically in several ways: Interoperability: The technical specification ensures that protocol information can easily be exchanged and understood between various electronic systems used by sponsors, investigators, and regulatory authorities through adherence to standardized data formats and structures. Efficiency: In general, when the clinical trial process undergoes electronic transfer of data on protocols there is less time taken to validate or enter data. Data Integrity and Quality: Having a standardized technical framework helps maintain data integrity and quality thus preventing inaccuracies and inconsistencies in protocol information. Regulatory Compliance: The technical specification makes sure that any electronic submission conducted meets the requirements set forth by ICH member regions; therefore, facilitating smoother and quicker regulatory reviews. Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/ Core Reference  CORE Reference is a user manual to help medical writers navigate relevant (ICH, and EU and US regional) guidelines as they create CSR content for today's studies, including detailed content suggestions and practical suggestions for developing CSRs that will require minimum redaction and modification prior to public Aim of the CORE Reference Project  To provide Continuous Professional Development (CPD) for the regulatory medical writing community through open access resources and intelligence dissemination on clinical study reporting and public disclosure of clinical-regulatory documents. Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/ Core Reference  What is CORE Reference? Authoritative open access user’s guide to support the authoring of CSRs for interventional studies Addresses ambiguity in ICH E3 CSR guideline 1995, and E3(R1) 2012 Q&As Presents practical suggestions for developing CSRs Sectional mapping tool companion to ICH E3 Not a template Ongoing surveillance of regulatory reporting and public disclosure landscapes; insights shared with the medical writing community Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/ Core Reference Background to CORE (Clarity and Openness in Reporting: E3-based) Reference Designated an EMWA Special Project in 2022 Registered with EQUATOR network in 2016 as a reporting guideline Initiated by the Budapest Working Group in 2014 Included EMWA and AMWA experts in ICH E3, CSR templates, CSR authoring, and public disclosure of clinical-regulatory documents Two-year collaboration with stakeholders to review the ICH E3 and subsequent regional guidelines impacting CSRs Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/ Core Reference Background to CORE (Clarity and Openness in Reporting: E3-based) Reference Designated an EMWA Special Project in 2022 Registered with EQUATOR network in 2016 as a reporting guideline Initiated by the Budapest Working Group in 2014 Included EMWA and AMWA experts in ICH E3, CSR templates, CSR authoring, and public disclosure of clinical-regulatory documents Two-year collaboration with stakeholders to review the ICH E3 and subsequent regional guidelines impacting CSRs Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/ Why to use Core Reference? To support authoring of disclosure-ready CSRs Help MWs interpret ICH CSR authoring requirements Highlights privacy-related risks associated with published CSRs Aids understanding of public disclosure requirements for CSRs Offers sectional content suggestions but does not mandate a particular CSR structure Shares regular updates on regulatory reporting and public disclosure Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/  CORE Reference Outputs Downloadable open-access resource Mapping tool which maps CORE Reference sectional content to ICH E3 Peer reviewed publication (2016) Growing CPD reference library  CORE Reference Keeps Medical Writers Informed Provides CPD for medical writers Subscribers receive regular CPD email with up to date information on regulatory reporting and public disclosure landscapes Creates a growing CPD reference library Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/ HL7 HL7 is a set of international standards employed for exchange, transfer, integration, sharing, and retrieval of electronic health care data between different healthcare providers. In the healthcare industry, a huge sum of data is produced daily. HL7's main goal is to promote interoperability and ensure all stakeholders within healthcare can communicate effectively and efficiently. The standards produced by HL7 lead to an overall better quality of care and increase patient safety by reducing the risk of medical errors Faculty and of Clinical improving Research the coordination of care. and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/ HL7  HL7 is a set of clinical standards developed by healthcare information standards organizations. It consists of several parts or profiles.  HL7 stands for Health Level Seven. It’s a collection of rules governing how hospitals and other medical facilities should handle patient data.  The information that HL7 provides allows for better communication. It also provides a framework for integrating electronic health records (EHRs) and patient care information.  They define the information structure and how it should be collected. Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/ Medical entities such as hospitals, doctors, and others must be able to send and receive various types of data such as patient information, medical images, as well as biomedical data such as ECG. Since medical data have different data formats and interface methods, these data must be presented in a standardized format to allow for exchange of information (HL7 Organization. [ http://www.hl7.org]; HL7 Version 2.5.1 Messaging Standard). HL7 (Health Level 7) is an ANSI approved standard that allows for exchange of medical data among computer applications. It is one of the most successful messaging standards in the medical field. The HL7 developed an international set of open standards for a message format and semantically interoperable data that allow different health information systems to easily and effectively communicate with one another (HL7 Organization. [ http://www.hl7.org]; HL7 Version 2.5.1 Messaging Standard). This standard deals with clinical observation, laboratory, pharmacy, medical devices, imaging and insurance transactions. It also provides the exchange, management and integration of data that support patient care and care management, as well as the delivery and evaluation of healthcare services. Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/ SPIRIT In medical writing, "SPIRIT" often refers to a set of guidelines designed to ensure transparency and completeness in reporting clinical trial protocols and results. Here's what "SPIRIT" stands for: 1.Standard Protocol Items: Recommendations for Interventional Trials The SPIRIT guidelines provide a framework for researchers to clearly and comprehensively describe all essential elements of a clinical trial protocol. This includes details on study objectives, study design, participant eligibility criteria, interventions, outcomes, statistical methods, and procedures for handling protocol deviations. Adhering to SPIRIT guidelines helps ensure that clinical trial protocols are well-documented, transparent, and reproducible, which is crucial for evaluating the validity and reliability of study findings. The SPIRIT 2013 Statement provides evidence-based recommendations for the minimum content of a clinical trial protocol. SPIRIT is widely endorsed as an international standard for trial protocols. The recommendations are outlined in a 33-item checklist and figure. Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/ SPIRIT- INTRODUCTION  High quality protocols facilitate proper conduct, reporting, and external review of clinical trials. However, the completeness of trial protocols is often inadequate. To help improve the content and quality of protocols, an international group of stakeholders developed the SPIRIT 2013 Statement (Standard Protocol Items: Recommendations for Interventional Trials). The SPIRIT Statement provides guidance in the form of a checklist of recommended items to include in a clinical trial protocol.  This SPIRIT 2013 Explanation and Elaboration paper provides important information to promote full understanding of the checklist recommendations. For each checklist item, we provide a rationale and detailed description; a model example from an actual protocol; and relevant references supporting its importance. We strongly recommend that this explanatory paper be used in conjunction with the SPIRIT Statement. A website of resources is also available ( www.spirit-statement.org).  The SPIRIT 2013 Explanation and Elaboration paper, together with the Statement, should help with the drafting of trial protocols. Complete documentation of key trial elements can facilitate transparency and protocol review for the benefit of all stakeholders. Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/ SPIRIT- INTRODUCTION  Given the importance of trial protocols, an international group of stakeholders launched the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) Initiative in 2007 with the primary aim of improving the content of trial protocols. The main outputs are the SPIRIT 2013 Statement,14 consisting of a 33 item checklist of minimum recommended protocol items (table 1​1)) plus a diagram (fig1​(fig1);); and this accompanying Explanation and Elaboration (E&E) paper. Additional information and resources are also available on the SPIRIT website ( www.spirit-statement.org). Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/ Example template for the schedule of enrolment, interventions, and assessments Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/ SPIRIT CHECKLIST SEPTRE (SPIRIT Electronic Protocol Tool & Resource) is an innovative web-based tool that simplifies the creation, formatting, and registration of high-quality trial protocols. The SEPTRE protocol tool incorporates automation and the evidence-based SPIRIT guidance to strengthen the quality, efficiency, and transparency of clinical trials. SPIRIT 2013 CHECKLIST (WORD | PDF) SPIRIT 2013 FILLABLE CHECKLIST (WORD | PDF) SPIRIT-Outcomes 2022 FILLABLE CHECKLIST (PDF) SPIRIT-Outcomes 2022 FILLABLE CHECKLIST (Extension items only) (PDF) FIGURE (WORD | PDF) Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/ Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/ Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/ TransCelerate TransCelerate BioPharma Inc. is a non-profit organization consisting of pharmaceutical companies working together to improve the research and development process for new medicines. In the context of medical writing, TransCelerate has contributed significantly to standardizing and harmonizing various aspects of clinical trials and regulatory submissions. Here are a few key aspects of TransCelerate's impact on medical writing: 1.Data Transparency and Sharing: TransCelerate promotes initiatives that enhance data transparency and sharing in clinical research. This includes guidelines and recommendations on how clinical trial data should be reported and shared to ensure transparency and accountability. 2.Common Protocol Templates: TransCelerate has developed common protocol templates that facilitate consistency and completeness in clinical trial protocols. These templates help ensure that essential information required for protocol development is captured Faculty of Clinical Research uniformly and Drug Safety across different trials. (FCRDS), IGMPI 3.Shared Investigator Platform: TransCelerate has http://www.fcrds.org.in/ developed a Shared Investigator Platform (SIP) that aims to TransCelerate 4. Quality by Design (QbD): TransCelerate promotes Quality by Design principles in clinical trials, emphasizing the importance of planning and designing trials with a focus on quality, efficiency, and patient safety. This approach includes guidelines and tools that support risk-based monitoring and quality management throughout the trial lifecycle. Overall, TransCelerate's initiatives in medical writing aim to improve efficiency, quality, and transparency in clinical research and drug development, benefiting both sponsors and patients. Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/ CTFG: Clinical Trial Facilitation Group. In medical writing, "CTFG" stands for "Clinical Trial Facilitation Group." This group is part of the European Medicines Agency (EMA) and plays a crucial role in facilitating the preparation, review, and approval of clinical trial applications across European Union (EU) member states. Here are key aspects of CTFG's role in medical writing and clinical trials: 1.Harmonization of Regulatory Requirements: CTFG works to harmonize regulatory requirements for clinical trials within the EU. This includes developing guidelines and recommendations that ensure consistency in the preparation and submission of clinical trial applications. 2.Coordination of National Competent Authorities: CTFG facilitates coordination among national competent authorities (NCAs) of EU member states. This coordination helps streamline the review and approval process for multinational clinical trials conducted within the EU. Faculty of Clinical Research and Drug Safety 3.Development (FCRDS), IGMPI of Guidance Documents: CTFG develops guidance documents and templates to assist sponsors in http://www.fcrds.org.in/ CTFG: Clinical Trial Facilitation Group. 4. Promotion of Best Practices: CTFG promotes best practices in clinical trial conduct and reporting. This includes guidelines on good clinical practice (GCP), data management, pharmacovigilance, and other aspects of clinical trial management to ensure patient safety and data integrity. 5. Support for Multinational Trials: CTFG supports the efficient conduct of multinational clinical trials by facilitating communication and collaboration among stakeholders, including sponsors, NCAs, ethics committees, and investigators. Overall, CTFG plays a critical role in enhancing the efficiency, quality, and consistency of clinical Faculty of Clinical Research and Drug Safety trial applications (FCRDS), IGMPI and regulatory submissions across EU member states, thereby contributing http://www.fcrds.org.in/ WHO ICTRP WHO ICTRP (World Health Organization International Clinical Trials Registry Platform) is highly relevant, especially when discussing clinical trial registration and reporting guidelines. Here’s how the WHO ICTRP intersects with medical writing: 1.Guidelines and Standards: The WHO ICTRP sets guidelines and standards for the registration of clinical trials. Medical writers involved in preparing clinical trial protocols, informed consent forms, and other regulatory documents need to be familiar with these guidelines. This includes understanding the required information for trial registration, such as study objectives, design, methods, interventions, and outcomes. 2.Transparency and Faculty of Clinical Research and Drug Reporting: Safety Medical writers play a(FCRDS), crucial IGMPIrole in ensuring transparency and http://www.fcrds.org.in/ Impact on Publication: Clinical trial registration and adherence to WHO ICTRP guidelines can influence manuscript preparation and publication in medical journals. Many journals require trial registration as a prerequisite for manuscript submission, and adherence to ICTRP guidelines ensures that the trial information is publicly accessible and verifiable. Patient Safety and Ethics: Medical writers may need to incorporate information about trial registration and ethical considerations related to ICTRP guidelines into documents aimed at regulatory authorities, ethics committees, and study participants. This ensures compliance with international standards and promotes patient safety and welfare. Global Collaboration: The WHO ICTRP facilitates global collaboration in clinical research by providing a platform where trial information from different registries can be accessed and compared. Medical writers may need to navigate these registries to gather relevant data or ensure consistency in reporting across multinational trials. Familiarity with the WHO ICTRP and its guidelines is essential for medical writers involved in clinical trial documentation. It supports the integrity, transparency, and ethical conduct of clinical research, thereby contributing to the advancement of evidence- based medicine and patient care. Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/ Faculty of Clinical Research and Drug Safety (FCRDS), IGMPI http://www.fcrds.org.in/