Description

By examining the frequency and characteristics of major objections related to clinical pharmacokinetics and Dose- Exposure-Response (DER) relationships in assessment reports for medicinal products submitted in centralized procedures to the European Medicines Agency (EMA), the purpose of this observational review was to examine trends in deficiencies in clinical pharmacology dossiers. MOs were characterized in terms of ATC code, orphan status, legal basis, molecule type, major objection topic, and whether scientific advice had been sought during development from initial assessor assessment reports from 2013 to 2018. At least one major objection related to clinical pharmacology was found in 23% of the 551 identified Day 120 assessments. Analytical techniques, dose-exposureresponse relationships, absorption, distribution, metabolism, excretion, comparative bioavailability, and bioequivalence issues were the most frequently mentioned topics. The high number of major objections highlighted the significance of a robust clinical PK dossier in the evaluation of marketing authorization applications. In order to ensure that aspects of bio analytical methods, comparative bioavailability, PK in the target population, and DER relationships are thoroughly addressed in subsequent applications for marketing authorization, this review ought to provide useful insights.

Assessments of Significant Differences between Populations

In public health, clinical trials play a crucial role in educating patients and healthcare professionals about the potential benefits and drawbacks of new medicines. When a diverse population is included in clinical trials, a drug's real-world performance is best guaranteed. Patients' confidence in medicines' safety and efficacy grows when they see themselves reflected in clinical trials. Access to clinical trials also contributes to advancing health equity because clinical trials are mentioned in some treatment guidelines, such as those from the National Comprehensive Cancer Network. Health authorities and organizations like the Pharmaceutical Research and Manufacturers of America (PhRMA) and the United States Food and Drug Administration (FDA) are working to promote and increase diversity in clinical trials by publishing recommendations on principles of trial conduct and communication and issuing guidance on the subject. Based on lessons learned from its COVID-19 vaccine program, Pfizer recently published proposals to increase clinical research equity. Pfizer made a promise to make sure that people who take part in its clinical trials are people of the same racial and ethnic background as the countries and communities where the trials are being conducted. In the United States, the goal is to have racially and ethnically diverse participants in all trials, regardless of the type of trial or disease area, at or above US census or disease prevalence rates. To identify disparities in clinical trial populations, a comprehensive baseline of US interventional trial participation was established through an analysis of Pfizer clinical trials conducted between 2011 and 2020. Race and identity dispersions across immunization, CP, and remedial region preliminaries were contrasted relative with information announced by the US Statistics Department for 2010-2019. The analysis revealed that not all disease areas or trials had equal representation of races and ethnicities, with certain racial groups not represented in some trials. These results served as a starting point for evaluating the success of diversity-related initiatives in all clinical trials. In order to provide early assessments of significant differences between populations, diverse representation in CP trials is essential. However, Phase 2/3 clinical trials, which are large enough to evaluate safety and efficacy across demographic groups and encompass a wider range of intrinsic and extrinsic patient factors, may provide the greatest benefit of trial diversity. Additionally, the patient may gain from these subsequent trials. Through an understanding of the intrinsic and extrinsic factors that influence exposure and response, clinical pharmacology has facilitated diversity in patient trials and will continue to do so. This paper examines additional CP-driven strategies for promoting racial and ethnic diversity in patient trials. In this instance, Pfizer makes a commitment to these actions and encourages other sponsors of clinical trials to adopt a similar framework in the effort to establish a standard for the industry. Patients with organ impairment, elderly patients, and pediatric patients, among others, can all benefit from the presented considerations and recommendations.

Components of Improving and Optimizing Drug Use in Health Care

Over the past few decades, drug development and use have become more complicated, increasing the demand for new clinical experts. Many of the following aspects of drug development and use prompted this change, which occurs concurrently with the development of clinical pharmacology and the demand for it: alterations and a variety of sources; high standards for drug research and discovery; seek more in-depth characteristics in order to address unmet needs at the individual and community levels; expectations regarding efficient use; identifying, resolving, and avoiding issues related to drugs; and rising demand for assistance in the laboratory and with information during their use. The World Health Organization took a series of CP-focused activities half a century ago to define the discipline and identify the main components of improving and optimizing drug use in health care services. Currently, many developed countries are known to have an established CP discipline that implements the health services expected from the discipline under various headings. These initiatives are developed to get the most benefit from drugs. Because each nation's facilities and requirements have a significant impact on these processes, the development and advancement of CP follow distinct global practices. The Clinical Pharmacology Society and the Clinical Pharmacology Working Group of the Turkish Pharmacological Society were the primary pioneers in accelerating substantial progress in Turkey toward the end of the 1990s, despite the fact that this field had been the subject of a number of distinct efforts to establish it before that. The country witnessed efforts to organize CP activities in the fields of education, research, and routine health care; however, these efforts did not result in a firm identification of the CP field. In terms of organizational structure, no significant progress has been made so far; In 2011, the Clinical Pharmacology Society lost its legal personality, and the majority of CP issues were implemented as a result of the unplanned efforts of CP-oriented pharmacologists (CPOPs). Despite this, CPOPs an estimated community of 200 people in Turkey—have been looking for more and more ways to guarantee that CP functions in an integrated, structured, and well-organized manner. The purpose of this review is to contribute to the development of a network of communication and collaboration as well as to provide practitioners from around the world, including those from Europe, with comprehensive information regarding CP practices in Turkey. In addition, it aims to inspire and lead not only the national community but also other nations that have not yet implemented CP by increasing awareness of the fact that CP directly or indirectly improves the quality of health services, spreading rational use of medicines to all stakeholders, assisting in the establishment of CP organizations or units at academic or other health-related institutions, cultivating a workforce of sufficient quantity and quality, and expanding facilities.