How do MOA Clinical Trials Contribute to Understanding Drug Efficacy and Safety?

Current evidence-based medicine focuses on clinical trials rather than considering mechanistic evidence data. Hence, scientific communities are addressing this imbalance by evaluating approaches that include mechanistic studies focused on mechanisms of action combined with clinical studies. Data on randomized control studies is usually available during drug development meetings. Evidence on mechanism of action studies is not common among these setups.

Nevertheless, mechanism of action studies are critical to all aspects of drug approval, including evaluating pharmaceutical quality, assessing efficacy and safety, designing dosage regimes, extending product licenses, complex assay results such as cytokine multiplex assays, etc. Mechanism of action (MOA) clinical trial data should be discussed while presenting data on clinical studies. The current article discusses the contribution of MOA clinical trials in understanding drug efficacy and safety. 

Role of mechanism of action studies in understanding efficacy and safety 

Understanding the mechanism of drug action, particularly its pharmacokinetic properties, is crucial to designing dosage regimes for individual patients. For example, treating deep vein thrombosis with anticoagulant enoxaparin, the approved dosage is relative to the patient’s body weight. This relation is because the rate of enoxaparin depends on the metabolism and renal functions, which tend to be influenced by the body weight. However, the clearance rate of enoxaparin depends on the lean body weight rather than the total body weight. This distinction becomes crucial when treating a broader range of patients in routine analysis. Treating obese patients based on their total body weight will put the patient at risk of increased toxicity. Hence, a deeper understanding of the mechanism of drug action can help design appropriate dosages for a specific patient population. 

The primary correlation between the mechanism of action studies and drug development is that as the clinical evidence about the mechanism of action and benefits becomes more compelling, it increases the success rate of drug progression through different stages of clinical development. This success is due to the merger of evidence obtained from the mechanism of action studies and drug benefits confirmed through rigorous randomized control trials. However, this merger during clinical development does not necessarily stop at the approval stage. 

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The questions clinicians and consumers have about a drug product extend beyond the rigorous evidence from randomized clinical trials. The primary questions consumers have are based on the evidence of drug benefit to the patient population, consideration about individual characteristics, safety for patients with impaired hepatic or renal function, adverse reactions depending on age groups, etc. Although studies conducted during drug development partially answer these questions, clinical outcomes and mechanism of action studies must evolve simultaneously to address all pressing concerns regarding the safety and efficacy of drug products. 

The road ahead for the mechanism of action studies

Today, developers are focused increasingly on evaluating a product throughout its life cycle. To do so, having relevant and reliable data for clinical outcomes and drug mechanisms is critical. Besides, technological advancements in approaches for clinical outcomes and the mechanism of drug action studies will be essential to instilling customer and regulatory confidence and developing safe and effective drug products.