Eteri Tsetskhladze, MD, PhD

	Immune-mediated inflammatory diseases (IMID) encompass a wide range of disorders. This includes multiple sclerosis, rheumatology disorders, psoriasis, inflammatory bowel diseases, COPD, pulmonary fibrosis and asthma, as well as immunosuppression within transplantation and other minor therapies and pathologies, and also some rare diseases.
	
	Significant and ongoing research into IMID pathology and genetic links have led to the knowledge that underpinning these diseases is the dysregulation of the immune system, which leads to widespread and chronic inflammation. These discoveries have delivered a more comprehensive understanding of immune-mediated mechanisms, and the promise for more effective treatments and possibly even cures for a range of IMID disorders.
	
	


	
	In the search for more effective treatments and cures, there are challenges that sponsors and contract research organizations (CROs) must confront when conducting IMID clinical trials.
	
	

Today, many sponsors and CROs are considering IMID clinical trial sites in non-traditional countries, due to lower costs, competition for investigator sites, and the search for naïve patients. While conducting clinical research in these countries can present real opportunities in the identification of naïve patients, they also can pose challenges when using less experienced investigator sites. To ensure success, CROs must conduct extensive investigator site training and deploy experts to adequately control and monitor the research program.
	
	

 Some clinical trial protocols are not consistent with clinical practice, making it difficult for investigators to comply. For example, in rheumatology clinical practice, individual rheumatologists may use a subset of joints to assess joint function in a particular patient as part of a global evaluation of patients’ condition. However, in a clinical trial, investigators must use a specific, prescribed series of joint assessments for all patients, and are usually required to be blind to other clinical information regarding the patient. Additionally, patients with no or limited previous exposure to biologics are typically to be recruited, making achievement of recruitment goals very challenging, as well as leading to a potentially important discrepancy between the patient population enrolled in clinical trials and the one that most likely will receive the drug once available on the market.
	
	Perhaps more so with IMID trials than other research programs, it may be time to move away from using standardized protocols and study designs. Instead, adaptive clinical trial designs or different study end points should be explored, to align with changes and advancements in the clinical management of a disease and its course.
	
	

Utilization of the full therapeutic armamentarium:

 There is evidence that in some developing countries, clinicians may switch from traditional yet relatively dated treatments, directly to the latest investigational drug, without exploring the full scope of other available treatments. This approach is one that wouldn’t be used in clinical practice and may have significant effects on the efficacy and safety of an investigational drug. When conducting trials in developing countries, appropriate vetting of investigator sites and extensive training of selected sites can help to ensure that suitable steps are being taken for the care and management of patients.
	
	

 Participating in these trials requires a significant commitment from the patients and investigator sites, involves complex protocols, and can compete with a wide range of currently available treatments, which means that the supply of investigator sites and willing patients can be quickly exhausted.
	
	In addition to exploring locations around the world in order to identify naïve patient populations, a CRO should have existing relationships with research networks, specialized treatment centers, and academic institutions. Additionally, connecting with patient organizations and engaging key opinion leaders can assist in site identification and patient recruitment. In addition, having local resources that are up-to-date on local regulation and reimbursement policies for supplying patients with RA therapies can help in selecting the most appropriate countries.
	
	


	
	Over the last 20 years, biological therapies have revolutionized the treatment of immune-mediated inflammatory diseases. More recently, while the development of new IMID drugs may have slowed, clinical trials exploring the potential of existing drugs, including changes in dosing regimens, drug withdrawal, drug combination, or self-administration, have become more common.
	
	In parallel, due to patent expiration, clinical development of biosimilars has been increasing. Such clinical programs, although less complex than those of originators, are still demanding in terms of the cost and need for patients, while also presenting new challenges, especially from a regulatory point of view. Conversely, the bar for development of new biologics has been raised, with regulators requiring demonstration of clinical benefit in terms of efficacy or safety of the new drug in comparison to already approved biological therapies.
	
	IMID indications that have always proved more challenging for drug development, such as lupus erythematosus, are also being more frequently pursued, with increasing evidence of the inadequacy of current study designs and clinical end points. These complexities contribute to increased competition for investigator sites and patients, but also can create different and new types of target patient populations, outside of those that have previously been considered.
	
	


	
	The future success of IMID drug development is reliant upon the close collaboration between the sponsor companies that are uncovering new compounds for study, and the CROs that often lead the execution of these important clinical research programs. Finding the right partner, with deep medical and scientific expertise, will ensure that promising new compounds can one day reach the millions of people who are suffering from immune-mediated inflammatory diseases around the world.
	
	For further information please visit 

, Vice President, Global Project Management, IMID Franchise, Global Clinical Operations
	

, Senior Medical Director, Medical & Scientific Affairs

Articles

In the search for more effective treatments and cures, there are challenges that sponsors and CROs must confront when conducting IMID clinical trials.

Eteri Tsetskhladze, MD, PhD

Articles

Exploring the Future of Clinical Research for Immune-Mediated Inflammatory Diseases