A Case for Standardization & Collaboration in ClinOps

Standing on the shoulders of giants has long been one of the most apt descriptors of innovation – used by the likes of Isaac Newton, Stephen Hawking, and forming the motto for Google Scholar, as well. It highlights how no single scientist is an island, and how discovery is a collective action. Yet the world of research still has a way to go in making its shoulders easier to stand on; this article will explore the need for a greater degree of harmonization in definitions, data standards, and transparency to facilitate more robust clinical research.

Terminological Standardization

One area of clinical research that is in need of standardization to improve interoperability and reproducibility is that of the terms and methods used. This is particularly important in complex fields of medicine, such as oncology.

A good example of where this is already happening is in the reporting of Tumour Mutational Burden (TMB). TMB is an estimate of the genetic mutations present in tumour cells; measurement of TMB arose when it became evident that high TMB was a biomarker positively correlated with responsiveness to immune checkpoint inhibitor therapies. However, assessing the degree to which a tumour has mutated is not a linear affair, giving rise to heterogeneous ways of reporting it. Initiatives to standardize the characterisation of TMB arose out of pressure from groups such as Friends of Cancer Research and Quality Assurance Initiative Pathology, which networked with multiple stakeholders throughout the globe to drive efforts for standardization forward.

Other initiatives also define areas of biology which are in need of standardized frameworks in future oncology studies – such as the Tumour Microenvironment (TME). The Alzheimer’s Association also founded the Global Biomarker Standardization Consortium (GBSC) over two decades ago. It regularly holds events where biomarkers that are uniquely relevant to Alzheimer’s Disease (such as cerebrospinal fluid and blood biomarkers) are discussed, and provides reference frameworks to coordinate their characterization. 

It is clear that biomarker standardization across all areas of the life sciences promises to accelerate clinical drug development, but also provide better diagnostic tools for patients – and early diagnoses are often associated with improved outcomes, particularly for chronic disease.

Harmonization across Regions

Perhaps the biggest indicator for more cooperation and common terms has been the COVID-19 pandemic, which has driven an unprecedented need to work internationally between not only different teams, but also across different regulatory authorities. The need for greater coordination across governments became particularly more important as different regulators adopted varying fast track or emergency routes towards vaccine approvals, and for other treatments.

Indeed, the burden of adjusting clinical development for different authorities results in greater overhead costs that could have been avoided, but also makes international trials unnecessarily difficult. The International Council for Harmonization (ICH), which celebrated its 30th anniversary this year, represents a growing initiative to bring government, academic and industry stakeholders closer together to achieve better alignments in their work. To date, it has published 67 technical guidelines and standards across areas spanning the entirety of the clinical process.

The WHO’s Solidarity trials for vaccines and treatments have proven the value of inter-regional collaboration in the clinical department, dramatically cutting down the time needed to evaluate which options worked, using adaptive trial designs. Yet the trials also elucidated the hard work needed to achieve all of this – with an entire WHO Trial Secretariat needed to provide support to all participant countries, and multiple other committees to ensure data safety and compliance.

Additionally, greater inter-regulatory harmonization across borders will inevitably lead to better enforcement of standards throughout the world – which will alleviate concerns about opaque supply chains and low standards manufacturing.

Research Transparency

Another significant hurdle to standardization is the frequent non-publication of clinical trials. Publication in peer-reviewed journals not only disseminates information about all findings to the wider research community (including those for discontinued trials), but it also provides another incentive for adhering to reproducible standards. While the FDA passed the Amendments Act which requires all applicable trials to report findings to a federal website, adherence is lax. 

Multiple reviews have been done on the subject: one indicates that of 585 registered large sample (>500 participants) trials carried out before 2009, 29% remained unpublished. Another inquiry by STAT found that 74% of industry trials and 90% of academic trials required to report their results to the FDA reported no, or late, results.

The reasons for non-reporting are systemic and multi-faceted. High profile journals are uninterested in featuring disappointing clinical trial reports. Industry is not attracted to the idea of publishing trials regarding failed products – as it gives the competition an edge on what products to avoid. Given these justifications, it is not difficult to understand why reporting and publication do not materialise; the work involved is significant, and no incentives to do it exist for the people who will be doing it. 

Better enforcement of the guidelines for reporting and publishing results is necessary – particularly when we consider that studies involve real people who volunteered to participate; real people who deserve to have answers and results.

Future Outlooks

What becomes increasingly clear is that, as our world faces ever more global problems, solutions must also involve global responses. harmonization in regulatory outlooks and international collaborations will be critical in resolving these – just as they are with the ongoing pandemic. Corollary to this, the industry stands to benefit from working to establish clearly defined standards and measures in research – particularly as the complexity of treatments targeting composite biomarkers grows, as we now see with personalized and precision therapies – especially immunotherapies. And lastly, transparency in trial reporting remains an urgently critical need; too many resources are already wasted duplicating trials which have been performed but were not reported.

The solution to all these challenges is common – better collaboration and communication across professionals in the life sciences sector will be pivotal in improving clinical operations. Proventa International aims to facilitate the best-in-class events to accommodate discussions on the latest challenges in the sector. Find out more below.

Nick Zoukas, Former Editor, PharmaFEATURES