Global Clinical Trials
Ranga Prakash, Director Medical Affairs, South East Asia, Miltenyi Biomedicine
The term Clinical trials refers to systematically investigating therapeutic interventions or medical devices across four phases (I-IV) to establish safety, efficacy, and tolerability prior to seeking regulatory approval from regulatory authorities such as the US-Food and Drug Authority (FDA) or European Medicines Authority (EMA). Phase I Clinical trials assess safety usually in either healthy or ill volunteers whereas Phases II-IV clinical trials target patient populations who are generally ill. Global Clinical Trials (GCTs) are large-scale studies conducted across multiple regions, spanning the globe from the U.S., EU, and Asia, to evaluate therapies in a diverse sect of populations. Conducting GCTs is critical in ensuring the investigational therapy’s broad applicability, addressing ethnic and geographic differences, and generating robust safety and efficacy data to support global market authorization.
1. How have global clinical trials evolved over the past decade?
Global clinical trials have undergone significant evolution over the past decade, primarily influenced by advancements in technology (artificial intelligence), regulatory harmonisation, and changes in trial designs. Some of the key developments include the expansion in Geographical diversity, and a substantial shift towards conducting clinical trials in emerging markets such as Asia-Pacific, Latin America and Eastern Europe primarily due to cost efficiencies, access to diverse population, faster patient recruitment and emergence of adoption of International ICH- GCP Standards to manage clinical trials. Programmes like the US FDA’s Breakthrough Therapy Designation and the EMA’s PRIME schemes support faster approvals for promising therapies. Regulatory agencies are increasingly accepting realwworld evidence studies alongside clinical trial data to support decision-making. In addition, agencies such as the US FDA and EMA have emphasised the need for more diverse patient populations to ensure broader applicability of trial results.
The COVID-19 pandemic necessitated remote solutions, catalysing a rapid shift towards virtual trials, which are now becoming mainstream. It has brought in the adoption and acceptance of risk-based monitoring (RBM) which focuses on monitoring efforts on critical data points and processes, thereby reducing overall costs whilst still maintaining trial integrity. Increasing tech innovations in the healthcare space such as the use of Big Data analytics and AI are helping many sponsored trials with designing predictive markers thereby reducing the risks of trial failure. Organisations such as the ICH have worked to standardise regulatory requirements, simplifying the process of conducting trials across borders. In summary, such key advancements have shaped the way clinical trials are run and managed in recent years.
2. What are the current key trends shaping the global clinical trials industry?
Several key trends have shaped the global clinical trials industry in more recent years; importantly innovations in healthcare technology and its quick adoption, patient-centric approaches weaved into the protocol designs, and emphasis on operational efficiencies to name a few have been gaining traction in the recent years. Some impactful trends are:
Decentralized Clinical Trials (DCTs): Both Big Pharma and biotech are increasingly using decentralised models, leveraging smarter solutions such as wearable devices, telemedicine consults for follow up visits, e-consent and e-COA (electronic clinical Outcome Assessments) to capture patient data and sentiments for instant data analysis. Combining traditional site-based approaches with decentralised elements help provide additional flexibility to sites and improve recruitment and retention of subjects, especially in studies that require a relatively long term follow up.
Use of biomarkers trials: Biomarkers are frequently being used, especially in oncology and rare diseases. Drug makers are using biomarkers and genetic profiling to identify suitable participants, thereby reducing the number of SF and dropouts during the study.
Adaptive Designs: This allows dynamic changes during a trial, such as modifying dosages during the trial or expanding patient cohorts based on interim data. These approaches have been particularly useful in oncology trials where treatments can be more personalised.
Real-world evidence (RWE): This helps assess treatment effectiveness in real-life scenarios. Utilising data from outside of traditional clinical trials to complement trial data is gaining traction as regulatory bodies are increasingly accepting RWE in drug approvals. This is exemplified by the FDA’s guidance on using real-data to support regulatory decisions.
Mutual recognition agreements (MRA): These agreements can expedite the approval process by recognising data and approvals from a regulatory body in another country, reducing the redundancy in trials. All such trends collectively highlight an industry shifting towards greater efficiency, inclusivity, and technological advancement, with a strong emphasis on patient-centered care and global collaboration with the key intention to drive better and quicker outcomes.
3. Which regions are emerging as new hubs for clinical trials, and why?
Several regions are reshaping the global clinical trial landscape, driven by a combination of factors such as population diversity, cost-efficiency, increased adoption of technology, and supportive regulatory environments. Asia -pacific (APAC) countries such as China, India, South Korea, Singapore, Indonesia and Vietnam are gaining immense traction. These countries offer access to vast types of diseases, relatively untapped, treatment-naïve patient populations and increasingly better access to healthcare. Post-pandemic these countries are able to recruit patients quicker due to their access to a larger patient population. They have become a very attractive destination due to lower operations costs compared to the western markets. In recent years, we have seen increased investment in establishing good clinical trial infrastructure with modern facilities including access to Globally trained experienced Investigators, nurses and study coordinators in these countries. In the recent past, both China and India have streamlined their regulatory processes which allow them to receive approvals to begin Clinical Trials quicker in comparison to years ago where one would have to wait up to 1-1.5 years to receive approvals from Health Regulators.
The APAC region has experienced significant growth in clinical trial activity over the past decade with the presence of mega-hospitals in urban centers. Between 2017 and 2021, over 70,000 new clinical trials were registered across the APAC, the US, and the EU5 countries. Notably, the APAC region accounted for more than 50 per cent of these trials, indicating a substantial increase in clinical research activity. This growth represents a compound annual growth rate (CAGR) of 14 per cent for APAC region surpassing the marginal growth observed in the US and negative growth in the EU5. As of 2024 there are more than 16,000 registered clinical trials in the region showing continued expansion of APAC markets. Countries in Latin America such as Brazil, Mexico, Argentina, and Colombia have lower competition for trial participants and higher prevalence of certain diseases which facilitate rapid enrollment. These nations are harmonizing regulations to attract more international trials to boost access to specialised medicines with increasing interest in chronic diseases and oncology. Finally the emergence of specialised niche CROs with presence in these regions have made it easier for sponsors to support trial expansion. This global shift is fostering these emerging regions in becoming key areas to run global clinical trials, offering access to diverse populations and new opportunities for innovation while addressing unmet medical needs.
4. How do differing regulatory frameworks impact trial timelines and costs?
Differing regulatory frameworks across markets and countries significantly impact clinical trial timelines and associated costs in many ways, one of which is regulatory approval delays., Diverse approval processes in different countries along with varying document requirements for protocol approvals, ethical reviews, and trial documentation can be daunting. This lack of harmonization leads to prolonged timelines as sponsors adapt to each system. Some examples include:
Re-review of data: Some regulators require additional analysis or formats for data submission, even if the trial has been approved in other regions. For example, Japan often requires bridging studies for local populations; additional toxicity data requirements for some South east Asian countries etc. delay trial initiations.
Clinical hold risks: Regulatory agencies may impose a “clinical hold” if local requirements (such as site inspection standards or safety data) are not fully met, causing significant delays.
Localised documentation and reporting: Countries often mandate language-specific submissions, localised patient consent forms, various trial insurance and liability coverage and/or region-specific trial designs. All of these increase the administrative burden and associated costs for global sponsors.
Differing Standards: Regions have unique standards for Good Clinical Practice (GCP), ethical approvals, and patient safety. Aligning with these does require protocol modifications and investments on additional staff training.
Site activation delays: Regulatory approvals in multi-country trials often proceed at different paces, delaying the activation of some sites and thus dragging the overall recruitment process.
Longer Time to Market: Trials in markets with stricter frameworks or additional regulatory requirements (e.g., Brazil, China, Japan) take longer, delaying product launch and market entry. Navigating and proactively addressing these regulatory landscape challenges does require strategic planning, local expertise and sometimes significant investment in compliance and adaptation.
Blurb: Competing studies specifically in trial centers in US and Europe with a high concentration of CT leads competition amongst the same patient pool and favoritism amongst physicians leads to delays in patient recruitment.
5. What are the most significant challenges in patient recruitment for global trials?
Patient recruitment remains one of the most significant challenges in global clinical trials, often delaying timelines and increasing costs.
Some of the most critical issues and its underlying factors include:
Lack of trial awareness: Many patients and healthcare providers are unaware of the available clinical trials, especially in newer emerging markets. Some others don’t have a full understanding of the risks and benefits of enrolling a patient into a clinical trial. Likewise, stringent eligibility criteria applied on clinical protocols make it challenging to find patients that meet all the strict inclusion criteria. Many times the protocol inclusion criteria does not take into account the regional nuances due to heterogeneous treatment options resulting in poor recruitment.
Geographical and logistic barriers: Patients in rural and remote areas often lack access to trial sites especially in low to middle income countries and often need to take long journeys to visit their nearest health care center. Frequent needs for physical follow-up visits to trial sites and protocol related lengthy procedures often discourage participation.
Competing Trials: Regions such as the US and Europe have a high concentration of clinical trials within the same hospitals leading to competition amongst the same patient pool. Overlapping recruitment efforts and favoritism lead to significant recruitment delays. There are significantly lower patients in trials that require treatment-naive subjects.
Disease-specific challenges: Fragmented patient pools, specifically for rare diseases, are particularly challenging due to the scarcity of eligible patients globally. Patients with chronic conditions who have a stable disease often hesitate to participate in trials that require them to change their treatment regimens. Addressing some of these challenges requires a collective collaboration between sponsors, CROs, principal investigators, and patient advocacy groups, alongside leveraging technology and cultural insights to streamline recruitment and improve overall positive patient experiences.
Some of the strategies to overcome these challenges include: Taking patient-centric approach: Engage patient advocacy groups wherever available and patient communities to build trust and raise awareness amongst patients. Simplify trial protocols and provide flexible participation options (e.g., decentralized trials, tele consults). Technology integration: Use artificial intelligence (AI) and predictive analytics to identify eligible patients and optimise recruitment. Leverage social media, patient advocacy ambassadors and digital platforms for a targeted outreach.
Cultural sensitivity: Tailor communication to suit local languages, customs, and cultural norms. Equip local investigators with tools and guides to effectively recruit and engage patients seen in their daily clinics.
Financial and logistical support: Provide adequate transportation costs, childcare, and reasonable financial compensation for time and travel.
Diversity initiatives: Proactively engage with underrepresented groups to ensure trials reflect real-world populations.
6. How can pharmaceutical companies, CROs, and regulators collaborate more effectively in global trials?
Pharma companies, CROs, and regulators can enhance collaboration in running global clinical trials by leveraging innovative approaches, aligning on shared goals, and implementing system checks and balances to address inefficiencies throughout the duration of the clinical trial. Early regulatory alignment whereby sponsors can involve regulators early on in trial planning through pre-submission or pre-IND meetings have proven to be the key in achieving a favorable outcome. For example, Gilead Sciences collaborated with the FDA and EMA early during the development of remdesivir, expediting global trial approvals for COVID-19. Companies like Novartis worked closely with the FDA during the development of Kymriah (breakthrough CAR-T therapy), achieving rapid approvals through collaborative trial designs. The EU-PEARL Consortium is a one such collaboration between the EMA, pharma companies, and academic institutions to establish a framework for platform trials in Europe. This initiative has streamlined drug development in complex therapeutic areas like rare diseases. Engaging in Public-private partnerships to address patient recruitment and collaborative programmes that pool resources to educate and engage diverse patient populations globally. Including them in early discussions to ensure trial design is feasible from a patient’s perspective can also be communication to regulators to justify certain trial elements. One such example is the COVAX Facility for Vaccine Trials, a partnership between WHO, pharma companies, and CROs ensured equitable access to vaccines and optimized global patient recruitment during the pandemic. The collaboration included regulatory harmonization for fast-tracking approvals under special circumstances. Global regulatory capacity building training programs where PharmaBiotech companies and CROs invest in training programmes to familiarise regulators with innovative trial designs and technologies. For example, AstraZeneca had collaborated with a few regulatory bodies in Asia to train them on decentralized clinical trials (DCTs), ensuring alignment on expectations. Timely and frequent consultation with regulatory bodies have a positive impact on regulators and builds equitable mutual trust.
7. How will ongoing trends, such as personalised medicine, shape future trials?
Personalised medicine is poised to play an increasingly profound impact in the future design of clinical trials, largely driven by advancements in genomics, biotechnology, and data analytics. While precise projections of its share in upcoming trials are challenging, current trends indicate substantial growth in this area.
Personalised medicine market expansion: The global Personalised medicine market was valued at approximately USD 529.28 billion in 2023 and is projected to grow at a compound annual growth rate (CAGR) of 8.20 per cent from 2024 to 2030. Gene and cell therapies are expected to generate nearly US$54 billion in sales by 2029, with the cell therapy market also anticipated to surge to over US$52 billion in the same period, up from just US$3 billion in 2022.
Personalised medicine in clinical trials include personalised cancer vaccines: Researchers are developing vaccines tailored to individual patients’ tumour profiles, aiming to elicit strong immune responses against cancer-specific proteins.
mRNA vaccines for cancer: Clinical trials are testing mRNA vaccines against various cancer types, including melanoma, ovarian, head and neck, colorectal, and lung cancers.
N-of-1 trials: These involve single-patient trials to determine the most effective treatment based on individual responses, exemplifying the move towards highly Personalised therapeutic strategies. The integration of personalised medicine into clinical trials signifies a paradigm shift towards more tailored and effective therapeutic interventions, with ongoing research and technological advancements continually expanding its scope and impact. Adoption of personalised medicine will transform trials into smaller, smarter, and faster endeavors, leveraging technology and data to deliver highly targeted therapies. These trends will not only improve patient outcomes but also revolutionize the way drugs are developed, approved, and deployed globally. While some can argue that Personalised medicine can potentially lower costs by reducing trial sizes and focusing on likely responders, the initial investment in genetic testing and Personalised diagnostics might increase trial costs. However, this can be offset by more efficient drug development and reduce post-market failures. Constant collaboration between biopharma, diagnostic companies, CROs, and academic institutions will be essential to advance Personalised medicine trials.
8. What steps can companies take to ensure better trial outcomes in the future?
Pharma and biotech companies are always looking at several strategic ways to ensure better global trial outcomes due to high capital investment especially for their pivotal studies. These actions involve improving trial efficiency, fostering collaboration between CROs and providers, leveraging newer technology, and adopting a patient-centric approach. Some key steps taken include strengthening the planning and strategy by conducting comprehensive feasibility Studies by analyzing geographic, cultural, and healthcare system nuances to select the most appropriate regions and sites to run their trials. The use of Big data analytics to see past performances of trial centers in similar therapeutic areas thereby mapping their true recruitment potential is another significant step towards making smarter choices in selecting trial sites. Developing contingency plans for challenges such as geopolitical issues, regulatory delays, or recruitment shortfalls by selecting back-up countries should such a need arise. Carefully mapping out the Patient Journey by understanding the patient needs and barriers in targeted regions to design trials that maximize participation. Using the decentralized trials approach by incorporating both hybrid or fully decentralized trial designs to reduce logistical burdens on patients thereby decreasing the number of dropouts. Actively recruiting underrepresented populations to ensure diverse trial cohorts that reflect real-world demographics has become increasingly important to regulators. Use of innovative and adaptive trial designs such as platform, basket or umbrella trials to improve efficiency and flexibility when it comes to endpoint adjudication. Simplifying protocols to reduce complexity and streamline trial procedures to enhance patient and investigator compliance. Use of insights from past similar trial types to refine processes, protocols, and strategies for future studies. Engaging and partnering with regional key opinion leaders, healthcare providers, and patient advocacy groups to facilitate recruitment and execution. Seek active feedback on protocol designs from regional key opinion experts thereby decreasing the need to make fewer amendments during the trial phase. Conducting a thorough due diligence while selecting the CRO. Having experienced CRO project managers, credible regional presence and expertise in the therapy area is critical. Investing in training and capacity building by providing continuous education for CRO staff, site staff and investigators on protocol specifics, technology use and patient engagement. Investing in secure robust cybersecurity systems to protect sensitive patient and trial data from breaches especially with increasing malware and cyber fraud.
By integrating all these steps, pharma and biotech companies can overcome traditional challenges, enhance global trial efficiency, and deliver innovative therapies to patients more quickly. These approaches foster a balance of operational excellence, patient-centricity, and scientific rigor, ensuring sustainable success in the global clinical trial ecosystem.
9. How are companies leveraging technology and data to improve patient retention?
Pharma and biotech companies are increasingly leveraging technology and data to improve patient retention in clinical trials, ensuring that participants remain engaged throughout the study duration while optimizing data collection and trial outcomes. Some of the solutions include virtual participation using telemedicine, mobile e-consent, and remote monitoring tools. Patients can participate from the comfort of their homes, reducing the burden of travelling and long wait times at the hospitals. Home-Based healthcare services and home nursing visits for sample collection or drug administration enhance convenience and improves patient retention.
Wearable devices and gigital health tools, especially smartwatches and patches collect real-time health data, reducing the need for frequent site visits. Gamification apps with gamified elements encourage patient interaction and adherence through rewards track progress. Some Apps and online portals enable patients to access trial-related information, communicate directly with investigators, and receive updates on their health status. Predictive Insights more commonly known as machine learning tools analyze patient behavior and identify risk factors that might lead to dropout, enabling preemptive interventions. Tailored messaging and personalised communication, based on patient preferences and data insights, helps maintain engagement. Feedback Loops such as collecting patient feedback during the trial through surveys or mobile apps help sponsors identify pain points and implement improvements whenever possible. Leveraging Technology and data is a continuous learning leading to improved data quality and comprehensive data collection. Reduced drop outs translating to lower costs and significantly efficient trials. By adopting these technological and data-driven strategies, companies can create a seamless, patient-centric experience that not only boosts retention, patient trust but also contributes to the success of clinical trials which in turn accelerates the development of new therapies.
10. How is technology, such as AI or decentralised trials, transforming the clinical trial process?
Technology, particularly AI and DCTs, is revolutionising the clinical trial process by increasing efficiency, reducing costs, improving patient experiences, and accelerating timelines. Protocol optimisation, AI tools analyse historical trial data to recommend optimal study designs, reducing the likelihood of protocol amendments. Predictive modeling anticiaptes outcomes, patient recruitment rates, and potential challenges enabling proactive decision-making. Synthetic Control Arms and real-world data (RWD) can simulate control groups, reducing the need for placebo arms and lowering patient burden. Excientia for instance, uses AI to design adaptive clinical trials and prioritize drug candidates based on early data. When tackling the challenge of recruitment some AI tools identify eligible patients by analysing electronic health records (EHRs), social media data, genomics, and parsing huge datasets thereby improving recruitment speed and precision. Advanced analytics analyses data from multiple sources, offering actionable insights for trial optimization. There are regulatory AI tool offerings which continuously monitors data for protocol deviations or compliance issues and notifies the sponsors thereby reducing the risk of regulatory delays. AI uses multiple incoming data streams in real time for irregularities, enabling early intervention. This parallel processing of real time data and advanced analytics enable simultaneous evaluation of multiple trial components, speeding up decision-making. Blockchain technology ensures secure, tamper-proof data sharing and storage in multi-site trials. The integration of AI and decentralised trials is transforming the clinical trial process, making it faster, more efficient, and patient-centric. These technologies enable better datadriven decision-making, enhanced patient experiences, and broader access, paving the way for innovation and improved therapeutic outcomes. As adoption and innovation continues, these advancements will set new standards for the industry run clinical trials.
Author Bio
With a career spanning over 20 years in both Contract Research Organisations (CRO) and the pharmaceutical industry, Ranga Prakash has held key strategic Medical Affairs operational roles across leading organisations, including more recently at Miltenyi and Bristol-Myers Squibb (BMS)/ Celgene. Throughout his career, he has gained extensive expertise in managing and launching several new therapies in oncology, nephrology and neurology, bringing lifechanging treatments to patients in need thereby contributing to significant advancements in science.
