Lifelong Learning
This exercise covers the significance of drug trials in the process of creating new medications, the phases of drug trials, and the myriad ethical issues that may occur during clinical trials. It emphasizes important features of drug trials that the healthcare team—including physicians, nurses, technicians, pharmacists, and data analysts—must understand in order to interpret and grasp clinical trial results and use this knowledge to guide patient care.
One of the goals is to identify the various phases of drug studies.
Describe the moral and ethical quandaries that often occur during pharmaceutical research.
Briefly describe the clinical significance of pharmacological studies.
Explain the importance of interprofessional team collaboration and coordination in improving research outcomes, guaranteeing transparency, and assuring appropriate use of data from pharmaceutical trials.
Introduction
Drug trials are clinical research studies that are conducted on human subjects to evaluate the efficacy and safety of various drugs. Drug trials are carried out to assess current medications that warrant further investigation and comparison, as well as to seek for innovative and improved remedies for the prevention and treatment of different medical disorders. Blinding, randomization, appropriate power, and a clinically relevant patient group are regarded to be features of high-quality drug trials.
Function
Drug development refers to the process of introducing a new pharmaceutical product onto the market after its discovery, synthesis, or modification. It includes both human subject pharmacological trials and pre-clinical research.
Outside of humans, pre-clinical studies are undertaken to test medications on microbes and animals to determine their toxicity, pharmacokinetics, and pharmacodynamics. If additional research involving human participants is to be done in the United States, this information must be submitted to the FDA for approval of an investigational new drug (IND) application. In most other countries, the clearance process is similar. Once the IND application is approved, the experimental treatment is subjected to a series of human drug studies. If the medicine shows safety and effectiveness in phases I through III of the drug trials, the drug sponsor may submit a New medicine Application (NDA) to the FDA. The national drug regulatory agency chooses whether to grant the pharmaceutical final marketing approval after analyzing the application.
Human drug trials are generally divided into five phases, each containing at least one distinct clinical investigation. If a drug successfully completes phases I, II, and III of a drug study, the national regulatory authority will often approve it for general use. The whole medication development process might take several years to complete each phase.
Phase 0 trials are optional, exploratory, first-in-human investigations designed to determine whether or not the treatment has the anticipated effects on people as predicted by pre-clinical research. These studies help collect preliminary data on the pharmacokinetics and pharmacodynamics of the research medication in human subjects by providing low, nontherapeutic doses of the study medicine to a small group of volunteers (typically 10 to 15).
Phase I drug trials assess the experimental medicine’s safety. These tests assist in determining a safe dose range and identifying any adverse effects of the new medicine. Over the course of a few weeks or a month, a small group of healthy volunteers (often 20 to 80) are subjected to drug testing.
The efficacy and safety of the experimental drug are further evaluated in phase II clinical trials in a larger participant group (typically 100 to 300). Participants in phase II research with the target disease or condition are often included, and the trials span months.
After phase II trials give early proof of the drug’s effectiveness, phase III studies are conducted to provide final confirmation of the treatment’s safety and efficacy. The risk/benefit profile of the medicine is extensively investigated during this phase. It is often compared to medicines that are currently in use in a larger population (typically 1000-3000 patients) and for a longer period of time (usually six months).
Phase IV medication studies, which are undertaken after a treatment has been approved for marketing, offer more evidence of the risks, benefits, and optimal methods to use the drug. Post-marketing surveillance (PMS) studies are non-interventional phase IV studies mandated by the regulatory authority to validate the tolerability, safety, and effectiveness of a marketed drug in the real world. Post-marketing safety monitoring, in comparison to any other stage of a medication trial, enables the detection of any long-term or uncommon side events over a much longer time period and in a much larger patient group. Post-marketing surveillance studies aid in the intentional collection of clinical data relating to the use of a medicine in a broad range of patients, in addition to safety monitoring, providing information that may not have been obtained during phase III trials.
Investigator-initiated or academic clinical trials are clinical studies that are started and carried out by non-pharmaceutical company researchers, such as an individual investigator, a group of researchers working together, or an institution. Although sponsors may fund these studies, particularly if they believe it will provide support for a novel indication, the fundamental tenet of this type of clinical research is that the person who develops and conducts the study may be both the sponsor and the investigator. Investigator-initiated trials can obtain data on a drug’s effectiveness and safety in real-world settings. They are typically prompted by concerns from stages I through III of medication trials that have yet to be addressed.
Consider the Following Questions
In compared to conventional medical care, participating in a drug trial carries a greater level of risk, especially since there is a possibility of encountering unexpected adverse effects from a new prescription. Furthermore, there are other moral quandaries associated with pharmacological trials. These enigmas are sometimes caused by the fact that individuals who engage in the trials and bear the weight and danger are not the same as those who stand to gain from them.
The informed consent method is highly valued in modern research ethics. However, the concept of informed consent is sometimes questioned because it can be difficult to determine how much information should be provided to the participant in order for their consent to be valid, especially when it comes to a novel substance that hasn’t been tested before and may be associated with unknown risks. A person is given either too little or, in rare cases, too much information in a language that is too technical for them to comprehend.
Placebos are often used in pharmacological investigations. A danger associated with the use of a placebo is the possibility for harm to participants who get a placebo rather than a genuine treatment. If the person is not getting active treatment, their conditions may worsen, they may have greater suffering, or they may die away. As a result, the use of placebos is only permitted if there is no risk of the subject suffering significant or lasting harm.
Randomization is an important component in reducing bias in clinical trials. However, randomization between the two arms of a drug study might lead to serious ethical issues. Participants in a randomized controlled trial may be offered a treatment that later shows to be inferior. This is particularly problematic if the experimental drug turns out to be inferior to the standard of treatment available outside of the trial, or if the individual is given a placebo. As a result, participants may not get the most effective level of care possible.
Only clinically or statistically significant drug trial results are disclosed, which is known as publication bias. Unfavorable results are often not disclosed or publicized, resulting in an incorrect sense of a drug’s effectiveness. A pharmaceutical company, for example, that is supporting a medicine study may be able to assess the research results before they are released and may opt to postpone the dissemination of unfavorable findings. As a consequence, the scientific community is still unable to access the research data, making it impossible for healthcare practitioners to determine whether or not a certain treatment is appropriate for their patients.
Another issue to be cautious about during drug trials is sponsorship bias, often known as funding prejudice. A research is often financed by the pharmaceutical company that manufactured or funded the treatment. As a consequence, there is a conflict of interest since the company is inherently biased in favor of study results that would promote product sales.
Clinical Importance
Pre-clinical research may give essential solutions to safety issues, but it cannot replace trials that examine how a medication impacts the body. Clinical drug trials are often regarded as the major source of information on the safety and effectiveness of medicinal therapies.
The end goal of the drug development process is to market a new, significantly improved/altered molecule with proven therapeutic effectiveness. Because many suggested medications do not get beyond this stage, the transition from pre-clinical to clinical phases is critical. First-in-class pharmaceutical trials are also advantageous for doing the most comprehensive examination of the underlying causes of human sickness. Post-marketing surveillance helps monitor a medication after it is on the market and is used by patients in a variety of contexts and real-life scenarios, as opposed to carefully controlled laboratory conditions that are typical in pre-approval drug research. This ongoing study helps in determining the drug’s possible advantages and disadvantages.
Improving Healthcare Team Performance
Drug trials provide the most conclusive evidence of a medicine’s efficacy and safety in humans. This is only true if the trial activity is open, visible, and of good quality. The sponsor, local site investigators, the various Institutional Review Boards (IRBs) who monitor the study, and the national drug regulatory body are all accountable for a drug trial’s openness and the safety of research participants. To generate the most comprehensive and accurate data to inform clinical decisions and practice, all stakeholders must be aware of the myriad ethical and moral issues that often emerge in clinical trials and fulfill their responsibilities in conducting high-quality research. Furthermore, all stakeholders must properly understand the results of drug trials in order for them to be utilized ethically, appropriately, and appropriately in clinical practice.
It is the responsibility of every member of the interprofessional healthcare team to remain up to speed on clinical trials in order to use the most current data-driven models to guide patient care and question practices that are not supported by the most recent research. Because this responsibility must be specialty-driven, the focus on trials will be on studies that pertain to the provider’s field of expertise; clinicians will exhibit a significant interest in and demand for information about trials that deal with their specialized area. Similarly, if pharmaceutical trials are offered, pharmacists are more likely to investigate them if they are related to their areas of expertise. Nurses (especially those with specialty qualifications), PTs, even chiropractors, and other auxiliary medical practitioners should be able to share the most current pertinent research with other members of the healthcare team when required and/or appropriate. Everyone on the interprofessional team can only achieve their maximum potential for patient outcomes via open collaboration and communication. [Level 5]
