Strengths and Limitations of Non-Interventional Studies (NIS)

Non-Interventional Studies (NIS) are studies that reflect actual patient behaviors and how medicinal products are used in daily medical practice. Therefore, they observe clinical practice and does not define it. Since patients are followed in the real world, they can present comorbidities or other pathologies, and compliance status can vary.

Thus, these studies help fill the knowledge gap between clinical trials and actual clinical practice by providing a better understanding of the disease and a tool to characterize treatments and comprehend the economic implications.

This post aims to review some of the strengths and limitations of NIS:

Strengths & Benefits:

  • NIS take place in a real-world setting, with a diverse population, and few exclusion criteria.
  • These studies are a useful method for the collection of diverse information and can evaluate many clinically relevant outcomes, including some rare outcomes. NIS offer an efficient alternative to capture Real World Data (RWD) to support many evidence requirements, such as disease epidemiology, drug utilization, treatment patterns, safety, health economics, burden of illness, effectiveness, and many more.
  • Because we observe the real-world setting, these studies allow for additional comorbidities and comedications.
  • Comparators in NIS can also reflect the ones we have in real practice.
  • They can assess long-term effects and also rare events that cannot be evaluated in a clinical trial.
  • NIS are a continuous source of benefit-risk data, which is essential for all stakeholders.
  • They generate economic evidence, including cost-effectiveness, which is something very valuable.
  • With these studies, we can increase the knowledge and awareness of the disease, which, for example, can be useful for rare diseases.
  • NIS also help pharma companies to cultivate key customer relationships and to disseminate the new knowledge through publications and presentations. As a result, NIS help companies to establish and grow leadership in the therapeutic area.

As a consequence of all this, these studies have a strong external validity, meaning that the results are more generalizable than other studies in clinical research.

In terms of limitations:

  • NIS can be affected by the risk of bias. We can have several types of bias (such as selection bias and information bias), but a critical one is the confounding bias. Bias can be controlled and minimized by implementing the right study design and also through the statistical methodology.
  • NIS can show a compromised internal validity due to higher bias. Having a low internal validity implies that the causal relationship being tested is not completely trustworthy and can be influenced by other factors or variables.
  • The data quality may vary in these studies, especially due to the high amount of data that may not be available in a NIS.
  • Regulations are not harmonized for NIS. The regulatory requirements are very variable, and they are always evolving.

NIS are consequently an exceptional and efficient engine to generate Real World Evidence (RWE). Therefore, sponsors and clinical research organizations, such as Linical, are increasing their capabilities in this growing area of interest to meet the increasing demand for RWE and NIS.

NIS can be efficiently conducted with the right study design and the right operational model. In order to have a successful study execution, Linical provides the appropriate site management and monitoring approach, as well as the optimal financial provisions for these types of studies.

Nuria Moreno, PhD

Project Director, Late Phase

Linical Europe