Clinical Trials and the procedures of the types ?

Hi Readers! We have been listening these days from various media houses, ministers, world leaders and various other counterparts about the faster development of a new drug to combat against the coronavirus. These Durgs need to go through various phases of clinical trials before these are flooded into the market.

Kerala is the first state in India to run a race with the world for the clinical trials of convalescent plasma therapy. Whereas, the WHO and partners have started a “Solidarity” clinical trial for COVID-19 treatments. It is expected to reduce the time by 80%. It uses already existing treatments Remdesivir; Lopinavir/Ritonavir; Lopinavir/Ritonavir with Interferon beta-1a; and Chloroquine or Hydroxychloroquine. Unfortunately, discussing the intrinsic characteristics of these treatments is not my cup of tea. So, lets proceed to discussing the types of clinical trials in depth by which the efficacy of these treatments will be known.

Clinical Trials

A clinical trial is a research study conducted to assess the utility of an intervention in volunteers. Interventions may be diagnostic, preventative or treatment in nature and may include drugs, biologics, medical devices or methods of screening. Interventions may also include procedures whose aim is to improve quality of life or to better understand how the intervention works in volunteers. It is through clinical trials that the new drug gets approval from the concerned regulatory authority. Such trials are categorized as Phase I, Phase II or Phase III. Although these categories may not be mutually exclusive (nor in some cases mutually exhaustive), the objective of the types of clinical studies within each phase makes them mutually exclusive (or in some cases mutually exhaustive). At each stages of the trials, in the consent form, the subjects must be fully informed about the nature of the studies to be conducted, the research goals, the potential benefits, and possible risks.

Phase I Trials

Phase I trials, in most cases, consist of “early Phase I” trials which may comprise of early dose ranging trials, bioavailability (measurement of the rate and extent to which a drug reaches at the site of action) or pharmacokinetic trials, or mechanism of action studies. Bioavailability or pharmacokinetic studies and mechanism of action studies provide additional information so that the drug may be clinically used more effectively and safer in future studies. Early Phase I trials represent the initial introduction of the drug in humans, in order to characterize the acute pharmacological effect. For most classes of drugs, healthy subjects are enrolled, in an attempt to reduce the risk of serious toxicity and to avoid confounding pharmacological and disease effects. The idea is to introduce the drug to humans without inducing acute toxicity.

Phase II Trials

Phase II trials represent the earliest trials of a drug in a affected subject (patient). Patients should have the disease under investigation. Patients who enter such trials represent a relatively restricted yet homogeneous population. In some areas of drug development such as oncology (study of cancer), Phase II trials are categorized as Phase IIA and Phase IIB. Phase IIA trials may include clinical pharmacology studies in patients, and more extensive or detailed pharmacokinetic and pharmacodynamic studies in patients. Phase IIB trials are controlled and represent the initial demonstration of efficacy and safety of a drug at the doses from the clinical pharmacology studies. It is also used to estimate the effective dose range, to characterize the dose response curve, and to estimate the minimally effective dose. Often it is difficult to distinguish between Phase IIB trials and Phase III trials, particularly in terms of objectives. The primary differences are the inclusion/exclusion criteria and the sample size (number of subjects in trials).

Phase III Trials

Phase III trials may be viewed as an extension of Phase IIB trials. They are larger and the inclusion/exclusion criteria may be less restrictive than those of Phase IIB trials. For a drug to proceed to the Phase III portion of the development program, it must be deemed effective from the Phase IIB program. At this stage, effectiveness has been indicated, but not confirmed. The primary objectives of the Phase III program are to confirm the effectiveness of the drug in a more heterogeneous population, and to collect more and longer term safety data. Information from Phase IIB, provides pilot data for the purpose of sample size determination in Phase III. For the purpose of obtaining more safety data under conditions which better approximate the anticipated clinical use of the drug, a relatively large, uncontrolled, non-comparative (alternative) trials may also be conducted in Phase III. Since if the drug is given approval to be marketed, it may be used in the elderly etc., and since such patients are usually excluded from other trials, studies in special populations may also be conducted in Phase III.

Protocol of a Biostatistician/Statistician

Clinical trials give much significance on data analysis and the aspects of biostatistics is compatible to it. A protocol has to be developed for each clinical trial. An important responsibility of the statistician or biostatistician assigned to the protocol is to provide its statistical content. This includes: ensuring that the objectives are clear; recommending the most appropriate design (experimental design and determination of sample size) for the condition being studied; assessing the adequacy of endpoints to address study objectives; assigning participants to protocol interventions to minimize bias; and developing the statistical analysis. In addition it is imperative that the biostatistician provides a review of the protocol for completeness and consistency.

Thanks for reading :)

#clinicaltrials