Inflammation is an essential response to biological, chemical, or physical stimuli. Inflammatory diseases clinical trials that seek to unravel the cellular and molecular events involved in the inflammatory process encounter complexities associated with disease heterogeneity, weaknesses in study design, and a need for validated biomarkers. Such complexities contribute to high attrition, high costs, and slow drug discovery and development. Understanding study challenges and the underlying complexities is necessary for research teams, sponsors, and contract research organizations (CROs) to overcome them. Let’s explore how researchers and inflammatory diseases CROs address the complexities in inflammatory diseases clinical trials.  

 

Inflammatory Diseases 

Inflammatory diseases are characterized by diverse conditions, including autoimmune disorders, metabolic diseases, cardiovascular issues, and more. Conditions associated with chronic inflammation include autoimmune diseases such as rheumatoid arthritis (RA), metabolic diseases like Type 2 diabetes, cardiovascular diseases like hypertension, gastrointestinal diseases such as inflammatory bowel disease (IBD), lung diseases such as chronic obstructive pulmonary disorder (COPD), mental health conditions, neurodegenerative diseases such as Parkinson’s disease, and certain cancers.  

A recent convening of rheumatology experts identified clinical trial design innovation as a critical need across all rheumatology disease states. Significant unmet needs include innovative trial designs for RA precision medicine; the need to reliably phenotype and stratify patients for inclusion in OA clinical trials; clinical trial design innovations specific to systemic lupus erythematosus (SLE); and a lack of biomarkers to predict response or disease progression for vasculitis.

CROs emerge as indispensable partners in overcoming challenges with disease heterogeneity, intricate study designs, and the need for validated biomarkers, contributing to enhanced efficiency, reduced costs, and accelerated drug development.

 

Patient Recruitment Strategies: Leveraging CRO Expertise

Effective patient recruitment is a critical component of successful clinical trials. CROs, armed with their extensive experience, employ innovative strategies, such as leveraging social media platforms and optimizing digital solutions, to address the challenges associated with recruiting participants for inflammatory diseases studies.

Aily et al., looked at social media platforms as an avenue for patient recruitment in an osteoarthritis (OA) study, analyzing the conversion of clicks on a social media ad campaign to consent to enrollment. They found a low conversion from clicks to actual consent. However, 32% of the total sample required for the study consented expeditiously over five months at a per-subject cost well below traditional recruitment methods.  

 

Clinical Trial Design 

Clinical trial design innovations are imperative to address the evolving landscape of inflammatory diseases. CROs actively contribute to this aspect by introducing adaptive study designs, novel outcome measures, and efficient Phase II trial designs.

Observing the trend of Phase III lupus clinical trials increasingly failing to meet their primary endpoints after successful Phase II studies, Khalili et al., highlight issues faced at the patient, investigator, trial, study site, sponsor, and regulatory levels. Complexities identified include disease heterogeneity, weaknesses in study design, a lack of validated biomarkers, and composite outcome measures, which tend not to include patient-reported outcomes (PROs). To tackle these complexities, researchers introduced innovations such as trial designs that improve evidence-generation efficiency through fewer trials and patients while maintaining scientific rigor.   

Garces et al., reviewed SLE Phase IIb studies using adaptive study designs, which differ from traditional studies in several ways, including prospectively planned modifications at predefined interim time points. The researchers found that the adaptive design approach can reduce the number of Phase III trials needed, the total patient requirements, person-exposure risk, and ultimately, the time and cost resources required for drug development. 

According to Noor & Raine, IBD trials face a recruitment crisis due to multiple trials competing for the same participants. The authors call for Phase II trials that are more efficient in design, e.g., basket trials, which provide a greater appreciation of distinct clinical and molecular phenotypes of IBD, and outcomes, e.g., novel outcome measures that leverage advances in ex vivo analyses of biological samples.  

 

Human ex vivo Skins 

While inflammatory skin condition trials traditionally use animal models and reconstructed human epidermis, these models are limited in replicating the complexity of human skin. To address this, Wang et al., developed human ex vivo skins as experimental models that mimic various human inflammatory skin phenotypes, e.g., irritation response. These models can potentially contribute to creating therapeutic solutions for compromised skin conditions. 

 

Digital Solutions 

Noor & Siegel assessed virtual innovations to address IBD trial complexities, including solutions for increasing diversity, remote consent (eConsent) and recruitment, tech-enabled remote patient monitoring and data collection, remote medication delivery and administration, and remote clinical trial monitoring, amongst others. They surmise that adopting virtual tech may improve patient centricity and trial efficiency.  

Rajan et al., suggest that there is an urgent need for alternative approaches for novel drug discovery for RA, including computational approaches like connectivity mapping to enable the repurposing of FDA-approved drugs beyond their original indication.  

Evidence suggests inconsistencies in how traditional paper-based PROs are administered, compromising the quality of data captured. McMullan et al., studied the effectiveness, efficiency, and satisfaction of a novel electronic PRO (ePRO) system in a basket trial for treating inflammatory conditions. They concluded that most participants with an inflammatory condition found it easy to report their symptoms, while research nurses were also positive about the ePRO system.  

Choy et al., explored the processing of skin images using neural networks to make predictions and analyzed the accuracy of deep learning (DL) algorithms. They found that DL algorithms have high specificity and variable sensitivity in diagnosing skin diseases like psoriasis and anticipate that real-world, prospectively acquired image datasets with external validation will advance DL to become clinically valuable tools. 

 

Omics Approaches 

The application of omics approaches, such as metagenomics and other advanced technologies, is crucial in understanding the intricate dynamics of inflammatory diseases. Inflammatory skin disorders, e.g., psoriasis and atopic dermatitis, have been linked to imbalances in the skin microbiome. As indicated by Chen et al., studies on skin microbiome typically use 16S rRNA gene sequencing, which cannot provide sufficient information about microorganisms on the skin. Advanced technologies such as metagenomics and other ‘omic’ approaches have been explored to address this issue and provide comprehensive and detailed information. In addition, meta-omic studies can help CROs discover and better understand the complex inter-species and multi-kingdom dynamics that have yet to be explored.  

 

Drug Delivery 

IBDs, including Crohn’s disease and ulcerative colitis, affect the gastrointestinal tract of millions worldwide. Although probiotics have demonstrated the ability to minimize disease symptoms, they are limited in terms of stability and targeted delivery. As indicated by Lopes et al., micro- and nanoencapsulation technologies have the potential to improve IBD treatment. 

 

Novel Diagnostic Biomarkers 

The study by Tang et al., aimed to identify and validate diagnostic biomarkers for IBD using bioinformatics analysis and machine learning (ML) and to explore the relationship between diagnostic biomarkers and infiltrated immune cells. Study results implied that a potential diagnostic biomarker was identified. 

  

Drug Repurposing 

As inflammation involves multiple pathways, drugs currently on the market for other purposes may resolve inflammation and mitigate the impact of other disorders sharing similar underlying mechanisms. Collotta & Lucarini review the challenges of repurposing drugs and suggest that extensive research is still needed to overcome these hurdles.

 

Your CRO Partner: TFS HealthScience

In the landscape of inflammatory diseases clinical trials, CROs, like TFS HealthScience, play a pivotal role in addressing the complexities associated with diverse diseases. From innovative trial designs to advanced digital solutions and cutting-edge omics approaches, CROs contribute significantly to improving efficiency, reducing costs, and expediting drug development. 

Sponsors benefit significantly from partnering with experienced CROs like TFS to navigate the complexities of these clinical trials. From protocol design to submission of study documents, TFS is your full-service Inflammatory Diseases CRO partner with top scientific, medical, regulatory, and operational expertise. 

Connect with a TFS representative today to learn more about the solutions we can offer for your next clinical trial.