INCLUSION AND EXCLUSION CRITERIA IN CLINICAL TRIALS

 INCLUSION AND EXCLUSION CRITERIA IN CLINICAL TRIALS

Introduction

Clinical trials (CT) are conducted so as to determine the efficacy and safety of the novel medical intervention. To investigate this, the clinical trials usually follow a protocol detailing its purpose, design and organization. During this process, it is customary to include the criteria’s to either-include or exclude the patients’ participation in the trial. This is done to help in corroborating evidence that the investigational drug will have the safety and efficacy in patients on getting the approval. This population wherein the outcomes of the clinical trials can be generalized fairly are determined by the Inclusion / Exclusion criteria. 

 Inclusion & Exclusion Criteria

The need for complete and accurate information about the medical intervention necessitates the use of a broader inclusion and narrower inclusion criteria. This would help discover, the effects of the drug on the previously excluded subjects who would eventually go on to receive the drug from the market after its approval.

The Inclusion criteria comprises of the characteristics that define the desired population under study. This group generally includes subjects at with a specific disease or pathophysiology on which the clinical effect of the drug can be examined.

The Exclusion criteria comprises of the characteristics that rule out the subject participation in the trial for reasons such as safety. This includes subjects with comorbidities, taking concomitant medications or characteristics that have the possibility to mask the effect of the medical intervention.

Challenges 

The challenges pertaining to inclusion and exclusion criteria include: 

 Minimizing heterogeneity during clinical trials poses a challenge since this data may not give a correct estimate of the drug effect in a broader and diverse population. 

 When the selection criteria are restrictive and narrow, it limits possibility of any variability in the trial subjects unlike the diverse general population.  

 Narrow selection criteria increases the odds of finding the desired clinical effect by controlling the confounding variables.

 The risk-benefit understanding is reduced by the narrow selection of trial subjects and may not reflect with the population that will eventually take the drug after approval. FDA

 The subjects are required to travel to the clinical trial sites regularly which might also be accompanied with travelling costs which might be burdensome for some subjects.

 Elderly subjects, children, cognitively impaired  or subjects with mental illness  may face difficulty in understanding the potential risks-benefits of the study. Difficulty in obtaining the consent from these subjects & any additional administrative or financial burden may prove to be a discouraging factor to include them in the study.

 For subjects with comorbidities already on medications may not want to participate in a trial where they would be subjected to additional medical interventions.

Reasons for Exclusion of Subjects from Clinical Trials

The subjects are selected on meeting the eligibility criteria while keeping in mind the safety of the subjects. Some of the reasons for excluding the subjects from the study include, 

 Subjects with organ dysfunction are excluded from the trials as a preventive measure against any possible adverse effects. 

 Subjects with multiple chronic conditions are usually already on medications and may pose the risk of drug interactions with the investigational drug being studied. Furthermore, excluding such patients rules helps in deciding the actual safety and efficacy of the drug and whether the adverse effect, if any, is caused by the investigational drug or any pre-existing conditions. 

 Pregnant and Lactating women have traditionally been excluded due to the unpredictability of the investigational drug causing any adverse events in either the mothers and/or the newborns and fetuses. Additionally, the drug behaviour may also be altered by physiological changes in such subjects.

 The subgroups comprising on infants, children and adolescents are normally excluded for ethical reasons so as to safeguard their health and safety. 

 The elderly populations are often on multiple medications to treat various chronic diseases, conditions and physical impairments, hence are usually excluded from research. 

Improving the Inclusion / Exclusion criteria

In order to overcome the challenges of broad exclusion criteria’s and to improve the enrollment of trial subjects, the following approaches can be adopted.

 Improving transparency, communication and involvements of subjects in the clinical trials.

 Eliminating, reassessing and revising the eligibility criteria’s in which subject participation is limited.

 Advanced planning on the manner in which the children would be involved in drug development to evince their safety and efficacy their respective age group.

 By adopting un-blinded, open label studies, the drug safety can be evaluated wherein the drug will be accessible to a greater number of subjects.

 Broadening of the inclusion criteria by prospective adjustment of the dosage to include patient subgroups such as children, elderly, those with co-morbidities organ dysfunctions and disorders.

 By providing access to the investigational drug to subjects in immediate need, such those suffering with life threatening conditions.  

Conclusion

Traditional Inclusion and Exclusion criteria’s with subject’s safety as a priority, although effective, come with their share of challenges. Since post-approval, the drug is consumed by the actual, diverse population (unlike clinical trials), the current need is to broaden the eligibility criteria for better generalizability of the research findings. The investigational drug reaching a greater number of subjects during developmental stages, gives a better overall picture of the drug product. This can to be done by improving the eligibility criteria and better recruitment of subjects keeping in mind the ethical considerations.

References

1. Patino CM, Ferreira JC. Inclusion and exclusion criteria in research studies: definitions and why they matter. J. bras. pneumol. 2018; 44(2): 84-84. 

2 Evaluating Inclusion and Exclusion criteria in Clinical trials Public worksop: Workshop report. The National Press Club • Washington, DC • April 16, 2018. Available from Worldwide web: [https://www.fda.gov/media/134754/download] 

3. Available from Worldwide web: [https://www.slideshare.net/BrookWhitePMP/improving-inclusionexclusion-criteria-for-clinical-trials]

By-

Mir Amjad Ali Khan (M.Pharmacy)

Gorantla Tejaswi  (B.Pharmacy)

Student at Clinosol