From Fax to the Cloud
Imagine trying to conduct today’s clinical trial using the same processes we relied on in 1996. We didn’t have smartphones, electronic medical records, cloud-based software and even the internet was in its infancy. The last five years have brought some of the most significant updates to ICH guidance. To understand why, we have to look back nearly 30 years through ICH guideline regulations.
The world in 1996 still worked off dial-up internet, fax machines, paper CRFs, desktop computers and again…no smartphones. In the 1990’s most studies were conducted regionally. Patients had to physically go to a doctor office to be seen by a physician physically standing in that same building at that same time.
30 years later we can stream video calls to meet globally. Patients have telehealth options so they can be ‘seen’ from anywhere. Phase III trials can be massive including 35+ countries.
As technology, medicine, and patient expectations evolved, regulatory guidance must evolve alongside them.
ICH E3 guidelines originated with a purpose: to establish a standardized structure for Clinical Study Reports (CSRs) submitted to regulatory agencies. Before 1996 companies produced reports in different formats, creating challenges for regulatory authorities to review and make sound and responsible decisions.
E3 Standardization involved:
- Report Organization
- Required Sections
- Appendices
- Efficacy Reporting
- Safety Reporting
- Statistical Reporting
- Patient Listings
- Narratives
- Study documentation
The goal was to create one global CSR acceptable to all ICH regions. See ICH Harmonisation for Better Health information: ICH Official web site : ICH
Since the creation of E3 there have been many Q&A articles explaining that all studies are not one in the same. Sponsors should adapt the CSR to suit the study rather than forcing every study into the same structure. We now have Phase I studies, adaptive designs, basket trials and decentralized trials. One report can’t fit every study.
In 1998 the original ICH guidelines for E5 was created with the purpose of: instead of repeating studies in various regions for approval of an entire Phase III program, companies could perform a smaller study demonstrating that foreign clinical data also applied to the local population. In 2006 an official Q&A document shared that if sufficient participants from different regions are enrolled, regional differences may be assessed within one global development program rather than through separate bridging studies. This provides more efficiencies and cost savings.
In 1993 ICH E7 was officially finalized sharing the inclusion of older adults in clinical trials for medicines expected to be used by elderly populations. However, in 2012 in the official Q&A the document provides an even greater emphasis on older adults as the population is aging, geriatric prescribing is increasing and modern understanding of PK/PD has advanced. The guidance regarding how many older adults should be entered into the studies is dependent on many factors.
Recently, ICH E6(R3) has been changing how CSR content is generated. There is much greater emphasis on:
- Quality by Design
- Risk-Based Quality Management
- Critical-to-Quality (CtQ) factors
- Sponsor Oversight
- Data Integrity
- Digital Systems
While E3 still defines how a CSR should be organized, E6(R3) influences what is discussed within that report. Sponsors are increasingly expected to describe risk management, protocol deviations, oversight activities, and quality management decisions in a way that reflects the modern trial conduct.
Today, CSRs may need to describe more details such as decentralized or hybrid trial elements, remote monitoring, wearable devices, eConsent, electronic source data, etc. E3 still provides this framework, however medical writers are now challenged with the same framework for much more complex trials than ever imagined in the 1990s.
There is a much greater emphasis on transparency. Regulatory leaders are seeking clearer reporting, traceability due to technology as it relates to the data, explanation of protocol deviations, etc. The structure of E3 supports this but the complexity of communicating these within any structure is a challenge that clinical operations, biometrics, medical monitors and others are forced to discuss and still make forward momentum. E6(R3) has not come out of thin air, but more so a logical result of thirty years of evolution.
Any time AI is brought into a discussion there are many emotions. Emotions of excitement for what it will bring, fear for what is unknown, to actual data filled examples of positive use. Clinical trials are moving into a new era of technology advancement. This comes with its own fears, understanding and acceptance. The key is to use AI for the positives it provides, keep standards in place for checks and balances, and continuously monitor and improve as we have done for the past 30 years of technology advancements. We are not new to change, but change can be scary. We are not new to change, but change can be helpful.
More than AI, we have decentralized trials, remote monitoring, cloud platforms, wearable sensors, HER integration, Quality by Design and other clinical trial efficiencies and changes. Naturally, E6(R3) emphasizes flexibility, Quality by Design, participant focus, risk-based quality, and digital systems. All aspects of E6(R3) are attempting to provide quality to the ever-changing world. ICH will continue to evolve, however not for the sole purpose of change, but scientific progress demands it.
How do we approach this? Our teams will jump on board to think through regulatory changes in clinical trials in a completely different way. They will look at the trials from a different lens.
- Clinical Operations Teams will think about Quality by Design from protocol development through execution.
- CRAs and Monitors might shift from routine source verification to more targeted, risk-based oversight supported by centralized monitoring.
- Project Managers may coordinate increasingly global, technology-enabled studies with more vendors and data sources.
- Medical Writers may balance standardized reporting with the flexibility needed for innovative trial designs.
- Sponsors and CROs are and will be adapting SOPs, training, and quality systems to support modern expectations while remaining inspection-ready.
The ICH guidance has been driven by advances in science, technology, globalization and a commitment to protecting study participants while improving quality. Every revision reflects the realities of modern drug development. Successful studies are driven by balance between innovation and compliance. The organizations that embrace these changes thoughtfully will be better positioned to deliver high-quality studies and ultimately bring new therapies to patients faster.
Spark Clinical Research shares in the desire to drive this success. Spark understands that experienced professionals, thoughtful solutions and practical real-world knowledge are key to knowing how to prevent challenging situations. Whether Spark Clinical Research is supporting sponsors or CROs; we’re bringing the clinical operations, biometrics, medical writing, regulatory, safety/PV solutions right to you. They know how to navigate the evolving ICH expectations while maintaining quality, efficiency, and inspection readiness. We help organizations adapt to changing clinical trial regulations, implement Quality by Design principles, strengthen oversight, and successfully execute studies that meet today’s incredibly complex landscape.
It has been 2 years since Spark Clinical Research started. Thank you to our clients, consultants and partners in the journey! Spark Clinical Research Celebrates Two Years of Excellence! The regulations that have changed in only 2 years have come from decades of technology evolution. Although the name – Spark Clinical Research – might be relatively new, the professionals driving the Spark initiatives and support come with decades of experience just as the evolution of ICH guidelines is multiple decades worth of changes. Let us Spark your Trials! We’re here to help!
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