GCP update: advice on what to expect and how to prepare
The Guideline for Good Clinical Practice—an international ethical and scientific quality standard covering aspects of clinical trial design, execution, and reporting—has not seen a revision since November 2016. Considering all the changes the drug development field has seen in nearly every corner in the intervening six years, it might be high time for an update.
Many operations struggle to understand and implement such standards. To learn more, Outsourcing-Pharma spoke with Sonia Araujo, head of product management for LifeSphere Clinical at ArisGlobal.
OSP: Could you please share some of the ways in which the drug development industry’s understanding of the balance between advancing treatments and protecting patient safety has evolved over the years?
SA: For pharmaceutical companies, being first-to-market with a new drug carries long-term financial benefits and a greater market share. Hence, any delays in conducting their clinical trials and getting their marketing authorization can wipe out that potential advantage.
For patients, any delay in getting medicines and treatments to market can affect both their economic outlook and their health; perhaps being the difference between life and death for some individuals. As citizens, we’ve all witnessed in the media when clinical trials have gone wrong, or even when a drug on the market has led to significant adverse reactions in the wider population. Technology advances mean we are all more “in the know.” We understand our health data, we expect a certain level of patient care, and we want faster results.
And then there was COVID-19! The pandemic and the need for vaccines and medicines in a record short time has proven (in my eyes) that this industry can move faster whilst keeping robust safety controls.
OSP: How have regulatory agencies like the FDA and EMA kept pace—have they served as a leading voice/resource, lagged behind a bit, or a mixture of both?
SA: The complexity of clinical trials has grown dramatically over the last 20 years. According to Ken Getz and Rafael Campo, the number of procedures per patient in the period 2011-2015 jumped between 53% and 70% (depending on the study phase) compared to the period 2001-2005; and the number of patient visits grew between 25% and 29%. That is a lot of data to contend with, for sponsors and their CROs, and for regulatory agencies alike.
We all have our gripes with regulators sometimes but overall, I believe they have kept a good balance between securing patient safety and helping bring medicines to market faster. Take regulators’ move to risk-based approaches - this really is helping sponsors and CROs focus on the things that matter.
Another example is the new European Union (EU) Clinical Trials Regulation that entered into application earlier this year. Yes, I know, several years later than the original plan. But now it is out, there are several elements that should speed up clinical trials and ultimately positively impact patients.
For example, prior to the Regulation, sponsors running trials in multiple EU member state countries had to submit clinical trial applications separately to the national competent authorities and ethics committees in each country, to gain regulatory approval for their trial. Now, sponsors need only submit one application to run a trial in several EU countries.
OSP: How have technological tools like CTMSs helped?
SA: A modern clinical trial management system (CTMS) helps clinical operations teams accelerate timelines through better planning, staying organized, and reducing complexity. A CTMS facilitates better cross-functional collaboration between clinical operations, data management, and other teams to identify critical risks affecting trial quality or patient safety. Clinical teams can uncover hidden study risks with industry-standard questions and score study risks based on likelihood, impact, and detectability. As a result, a more airtight risk plan strengthens a clinical study report and ultimately increases the study's success.
OSP: What other technological advancements have helped in designing and executing more effective, safer trials?
SA: Trial master files (TMFs) play a crucial role in the success of clinical trials, and the evolution of electronic TMFs only improves the process. eTMF systems offer automated tools and capabilities needed for the most efficient clinical operations by aligning clinical documentation with regulations and study protocols in a single source of truth.
An eTMF system also streamlines TMF inspections to quickly and efficiently handle complex audits. Maintaining compliance with embedded workflows and dashboards allows for easy trial reconstruction. And let’s not forget sites and their equivalent investigator site file (ISF). When the site’s eISF is integrated with the sponsor’s eTMF, the compliance adherence and efficiency gains multiply for both stakeholders. This is also an example of where technology can support stronger relationships between sponsors, CROs, and sites.
OSP: Could you please tell us about GCP guidelines—how they’ve supported clinical trial design and execution in the past, and what’s covered in the revisions this time around?
SA: GCP standards help organizations control quality while developing cutting-edge drugs. The ICH plans to release a revision of the GCP guidelines in August 2023 - the ICH E6 (R3) guideline. As before, the guideline will describe the responsibilities and expectations of all stakeholders in the conduct of clinical trials.
The revision focuses on two goals – ensuring patient safety and maintaining data integrity – acknowledging the increased diversity of trial designs and data sources. Diverse data sources — such as trials using master protocols, adaptive clinical trials, and decentralized clinical trials — continue to grow in number. Health authorities have expressed concerns that this data diversity introduces new risks. The ICH wants to ensure these risks do not outweigh the benefits of new drugs and medical devices.
OSP: Please talk about some of the obstacles smaller operations face in this.
SA: Smaller life science organizations sometimes struggle to meet the GCP guidelines due to limited resources, time constraints, and budget concerns. For example, it is common that staff in smaller organizations wear several hats and sometimes without the collective knowledge base present in larger pharmas. Often, multiple spreadsheets and documents are used to monitor milestones and manage risk, to keep costs down.
Other common obstacles include immature data infrastructure and fear that operationalizing a digital strategy could hamper productivity and negatively impact their level of competitiveness. Engaging CROs and software vendors who know business best practices may help smaller organizations overcome these obstacles.
OSP: What about helpful technologies—are these becoming more accessible to more modest operations, or further out of reach?
SA: Today’s technologies like CTMS, eTMF, and EDC systems help organizations of any size achieve their goals and stay in compliance. They help with risk management, cost reduction, and efficient conduct and safety of clinical studies. We have seen a rise in software vendors for those solutions, which has helped technology be accessible to many more organizations, more targeted to different organizations’ needs, and at different price points.
Speaking plainly, if organizations want to make strides in the life sciences industry, they cannot afford to stay disconnected throughout the process. A key consideration for smaller organizations would be to find a solution that is scalable and can grow with their changing needs.
OSP: How can a company like ArisGlobal help operations of various sizes make their way successfully and compete with the bigger guys?
SA: Small to medium-sized operations feel the pressure when bringing their first therapies to market. As deadlines quickly approach, an organization’s success and momentum depend on preparation. When using our LifeSphere platform, a company plants roots in a technology partner that will grow with them and support them at every crucial stage of research and development. LifeSphere streamlines countless data sources, brings efficiencies to distributed teams, and ensures compliance with global regulatory agencies.
OSP: Do you have anything to add?
SA: To quote the ICH, “Clinical trials should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with good clinical practice (GCP) and applicable regulatory requirement(s).” Much more data is nowadays collated during clinical trials, which ensures better outcomes but causes challenges for sponsors, CROs, sites, and regulators.
Despite that, patient safety remains key! Our industry has powerful technology to partner with to ensure clinical trials are accelerated by de-risking, whilst remaining compliant with guidelines and regulations like the forthcoming ICH E6 (R3) guideline. CROs play a vital role in this engagement, ensuring our industry thrives for the benefit of all stakeholders.