Introduction:
Drug safety assessment and efficacy evaluation are required in pre-marketing trials that are limited in size and duration. These trials also exclude high-risk populations. They have limited statistical power to detect rare but potentially serious adverse events in real-world patients.
Randomized controlled trials are mainly designed to give reliable information on the efficacy and safety of the drugs. They are considered the main basis of regulatory approval for a drug in the United States. All drugs and medical products have risks associated with them, along with the possible benefits. For the development of new medicine, the risks and benefits both have to be evaluated properly. The risk associated with the drug can be minimized when the safety and efficacy of the drug are well established before it is used for the general population.
In 1961, it was realized that international efforts were required to address drug safety issues after the Thalidomide disaster. Several guidelines were developed for monitoring drugs, foods & environmental contaminants for toxicity and adverse effects. Initially, these guidelines were restricted to specific regions. However, with globalization, guidelines were made to be followed and accepted internationally to ensure the safety and efficacy of medicinal products.
What Is Drug Efficacy?
The efficacy of a product can be defined as its potential to yield therapeutic benefits. Interventions that might be used include medical devices, drugs, surgical procedures, and public health interventions. Usually, the comparisons are made in randomized clinical trials.
In pharmacology, efficacy is defined as the maximum response that can be obtained with a drug. The effectiveness of a drug is in two distinct methods, including method effectiveness and use effectiveness. Method effectiveness is the maximum response that is achieved as a result of taking the drug exactly as prescribed, while use effectiveness is the response obtained when the drug is used under specific circumstances when adherence to the drug might not be 100 percent.
How Is Drug Safety Assessment and Efficacy Evaluation Established?
In clinical trials, critical safety and efficacy endpoints are established in advance, and an estimate of the sample size is taken to assess the effectiveness. In the United States, approximately 500 to 2000 patients are administered a new drug during clinical trials, with around only a few hundred of them being treated for more than three to six months. Common adverse effects are usually evaluated and well-characterized in future trials. Delayed or infrequent adverse effects are characterized based on their severity and importance to risk-benefit assessment.
Safety evaluation while clinical drug development is not expected to characterize all the adverse effects, for instance, those observed in one in thousand patients.
Risks that may be missed during the trials include:
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Rare events.
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Adverse effects are observed in association with specific diseases.
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Adverse effects that occur after long-term use.
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Effects were seen in special populations.
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Effects of concomitant drug therapy.
What Are the Safety Concerns During Clinical Trials?
The safety information on drugs approved for the market is mentioned in the product labeling. The pharmacology of drugs or pharmacologically related drugs can be helpful in identifying and exploring the major safety concerns, like the drug clearance pathway that indicates certain potential drug-drug interactions or some effects of reduced renal or hepatic function.
What Are the Adequate Sources for Safety Assessment and Efficacy Evaluation?
Information from all of the sources is screened properly, and side effects must be identified to indicate that some side effects occur more commonly observed than previously known or that certain patients are highly susceptible to some effects than others.
With the availability of new information associated with a marketed drug, the regulatory agencies review the data and evaluate any future drug safety concerns. If a potential drug safety concern is observed, the agency evaluates new safety information to find out whether there is an essential drug safety concern related to a specific drug or drug class and whether regulatory action is appropriate.
Various sources of information include:
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Spontaneous adverse drug reaction (ADR) reporting schemes.
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Clinical and epidemiological studies.
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Worldwide published medical literature.
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Pharmaceutical companies.
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Worldwide regulatory authorities.
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Morbidity and mortality databases.
What Are the Essential Criteria for the Safety and Efficacy of a Clinical Trial?
It is essential to know whether the subject is clinically fit for the trial or not because the safety of the subject is of prime importance. It is essential to apply investigation brochure findings for a prospective subject to certify this.
The fitness of the subject is decided based on inclusion or exclusion criteria and a thorough examination of the potential for drug accumulation or toxicities.
The inclusion or exclusion criteria:
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Medical history.
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Laboratory values.
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Concomitant medications used.
Examining the potential for drug accumulation or toxicities involves:
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Pharmacokinetics parameters.
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Single versus multiple doses.
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Linearity of exposure with dose escalation.
How Do the Adverse Effects Affect Clinical Trials?
Any untoward medical experience or occurrence associated with the use of a drug in humans must be recorded carefully during the trials. The worsening of any signs, symptoms, or the disease as a whole should be noted. The adverse effects severity grading scales provide general guidance on parameters to monitor safety and efficacy in clinical trials. They are associated with:
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Study population.
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The phase of product development.
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Product evaluated (therapeutic biologic, mall molecule, device, vaccine).
An adverse effect can be considered serious by the investigator or sponsor if the following outcomes are seen:
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Life-threatening side effects.
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Death.
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Patient hospitalization.
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Prolongation of existing hospitalization.
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A significant incapacity or substantial disruption of the ability to conduct normal life functions.
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A congenital anomaly or disability.
These adverse effects require intervention for permanent impairment or damage. Adverse drug reactions have an unwanted relationship with the medicinal product. The different types of adverse effects include:
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Suspected Adverse Reaction: Any adverse effect for which there is a possibility that it is caused by the administration of the drug.
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Life-Threatening Adverse Reaction: An adverse effect or suspected adverse reaction can be “life-threatening” if, according to the investigator or sponsor, it exposes the patient or subject to the risk of sudden death.
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Suspected Serious Adverse Reaction (SSAR): Adverse reaction that is classified as serious in nature as serious and consistent with information regarding the medical product used.
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Suspected Unexpected Serious Adverse Reaction (SUSAR): Adverse reaction that is classified as serious in nature but is not consistent with information about the medical product used.
Conclusion:
Safety assessment and efficacy evaluation of a medical product is a dynamic and ongoing process. It does not stop during the active life cycle of the product. During the premarketing phase of the drug, the chances of detecting the adverse effects are moderate. However, with the development of effective pharmacovigilance, unrecognized but clinically significant adverse drug reactions can often be detected, and adequate corrective measures can be taken. It is essential to communicate the risks and benefits through product labeling of prescription drugs.
