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How Clinical Trials Are Approved

How Clinical Trials Are Approved

Clinical trials are research studies that determine the efficacy and safety of consuming a certain pharmaceutical drug, treatment strategy or medical device.

These studies also increase medical knowledge by establishing the most effective medical trajectory that can be taken for a sample population suffering from special conditions, and all its possible outcomes, which can be used as future reference by any healthcare professional.

Clinical trials form the foundation of drug discovery and development. Data gathered from these clinical trials can be used reliably to aid healthcare decision-making and formulate drug regulatory protocols.

But in order to ensure participant safety a set of post-trial studies are conducted on small sample groups to investigate the new method for any harmful or unsatisfactory side effects.

Clinical trials are of various types, based on application - treatment, prevention, diagnostic, basic science, health services research, screening, supportive care.

Based on the design of the trial - observational or experimental - these studies can additionally be segmented into case control, systematic review, cohort, and randomized controlled trials.
For the clinical trial to proceed, the potential subjects must go through initial sieving (eligibility criterion). Before the participants sign the “informed consent” form prior to the study, they must understand all the risks - avoidable and unavoidable - and benefits of the outcome.

Aims of a Clinical Trial

The overarching objective of a clinical trial is the addition of a wealth of knowledge related to diagnosis, prognosis and prevention of ailment to medical journals.

To this end, clinical studies become pathways to evaluating one or more treatment interventions for treating a disease, syndrome or condition.

These goals can be expanded into four broader ones, which are:

1. Assess or discover modes of prevention or recurrence of a disease or condition.
2. Evaluate one or more diagnostic methods aimed at detecting a particular disease or condition.
3. Identify underlying risk factors of a condition.
4. Explore supportive care procedures to improve the quality of life of people with terminal or chronic illness.

More on Types of Clinical Trials & Their Importance

1. Treatment: Tests new treatments, drug combinations or approaches to surgery or therapy.
2. Prevention: Examines ways to improve prevention or recurrence of disease. Preventative methods may include medicines, vitamins, vaccines, minerals or even lifestyle changes.
3. Diagnostic: Finds improved, more efficient testing procedures for diagnosing disease and conditions.
4. Screening: Filters out the best method of identifying target ailment.
5. Health Services Research: Evaluates the delivery, process, management, organization or financing of healthcare.
6. Basic Sciences: Examines biochemical, biomechanical or physiological mechanism of an intervention.

Clinical research brings the element of evidence-based approach to modern medicine in order to improve treatment techniques and strategies, and, in turn, patient care.

Modus Operandi of a Clinical Trial

Clinical trials work on fixed protocols, with varying sub procedures.

A protocol, in medical terminology, is the written description of a clinical trial, which includes the study's objectives, design and methods.

1. Preparing for a Trial

a. Avoiding Bias

-    Comparison Groups: These groups are used in most clinical trials to compare medical strategies and treatments to see if one group has a better outcome than the other. This is usually conducted in one of two ways:

The group is split in two and given new and existing treatments, whose outcomes are then compared
Or, one group receives the new medicine while the second one receives a placebo

-    Randomization: This step involves the allocation of patients to comparison groups by chance rather than by choice.

It ensures that any difference seen in the results is purely due to strategy and not by choice.

-    Masking or Blinding: In this step, neither the participants nor the researchers are revealed the details of the treatment they are receiving.

If either the participants or researchers are unaware, it is referred to as "single blind;" and if both are unaware, it is termed as "double blind."

b. Designing the Trial

There are various kinds of studies, including cohort, case-control and nested case-control, cross sectional study, ecological studies, meta analysis, systematic review, experimental studies such as randomized control trials, adaptative clinical trial and non-randomized trial, and several others.

This article will elucidate on a few within its scope.

-    Cohort Study: A cohort is a group of people sharing some characteristics. In this form of research study, a group of affected people is selected and information on their particular, common characteristic which is allegedly causing the underlying disease/condition, is acquired; or, the common causal agent they have all been exposed to.

For example, if the study is attempting to find a treatment for lung cancer, the cohort might be a group of heavy smokers. People who smoke have higher chances of forming lung cancer. They are kept under observation to see how likely they are develop the cancer.

The main advantage of a cohort study is that multiple outcomes can be studied for any one exposure, and the disease in question can be analyzed for both exposed and unexposed groups.

-    Systematic Review: In this method, the medical research on a particular subject or condition is synthesized from its barebones.

This procedure is meticulous and excruciating as it involve deep, relevant research and studies from updated medical literature. The data retrieved is critically evaluated before using it to analyse conditions or diseases.

Although a sound, evidence-based research that produces extremely accurate results at lower costs due to use of already existing material, it can be time consuming and spell trouble for combined studies.

-    Meta-Analysis: A mathematical technique that combines individual study results to arrive at one inclusive overall measure of the effect of treatment.

Uncommonly used as a subdivision of a systematic review, this method draws from a large body of research and uses statistical analysis on the collected data.

It is useful when studies have conflicting results and in establishing statistical significance

It develops an accurate estimate of the magnitude of effect. It also shares similar advantages as systematic review.

Although a great analysis method with powerful results, this technique requires advanced statistical tools (software).

-    Randomized Controlled Trial (RCT): This method of clinical trial allocates individuals treatments or treatment and placebo.

RCT is the most successful method in identifying the most effective treatment and reducing the influence of external variables including bias, age, gender, weight, activity level, etc. can be canceled out.

It works wonders for large groups. However, they are subject to statistical errors (false positives and false negatives).

Hierarchy of Evidence

Systematic reviews and meta analysis are the most evidence-based studies while RCT does fairly good. Methods such as case-control studies are ranked at the bottom of the hierarchy.

Conclusion

There are several phases within clinical trials which are beyond scope of explanation. However, to summarize, these phases are:

1. Phase 0: Pharmacodynamics & pharmacokinetics analysis
2. Phase 1: Screening for safety
3. Phase 2: Establishing the effectiveness of the drug against a placebo
4. Phase 3: Final confirmation of safety & effectiveness
5. Peer review
6. New drug application
7. Drug labelling, approval and others
8. Phase 4: Sentry studies

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