Clinical research trials are the scientific bellwether to determine the safety and efficacity of the new pharmaceutical products that submit an application for approval to regulatory agencies. However, in the past decade many prominent researchers have questioned the bias against age, gender and race in the selection of individuals that wish to participate in these critical studies. Some good retrospective studies have studied those bias and their consequences in the studies. Most studies use a cohort of middle-aged white men that are progressively less representative of the general population in the USA, which has wide race, cultural and lifestyle differentials now.
Health Equity implies the attainment of fair, equitable access for health care services and the participation in clinical research trials that will determine the future of our modern pharmacopeia. It mandates the reconsideration as a whole of the protracted discrimination against minorities and special age groups in order to develop policy and practice protocols to assure equitable access.
In the USA the elderly population is growing rapidly due to the improved healthcare resources and the Wellness interventions in Baby boomers that consume less alcohol, tobacco, animal fat and other noxious substances that severely limited the lifespan of the previous generations. But the entrance to the third phase of our lives entails the arrival of diseases like high blood pressure, diabetes and arthrosis that do not similarly affect the younger and middle-aged members of society. When an elderly patient is admitted to a hospital , there are usually a few co-morbid conditions. Finally, the expense on elderly care represent the largest share of care budgets in modern societies.
Dr. Jaron Lockett et al. examined the Phase III clinical trials funded by the National Institutes of Health from 1965 to 2015 that studied the major causes of hospitalization or disability in older individuals, which are congestive heart failure, cardiac arrhythmias, coronary atherosclerosis, myocardial infarction, stroke, chronic obstructive pulmonary disease, pneumonia, lung cancer, prostate cancer and osteoarthritis. They found that 33% of these studies had arbitrary age limits that excluded older people and 67% of them had participants witha median age that skewed younger than the usual age of onset for the clinical condition being studied . The presence of co-morbid conditions like polypharmacy/concomitant medication excluded 37% of the cases and cardiac diseases excluded 30% of the potential participants. This underrepresentation of older individual due to age limits and exclusion of patients with common co-morbid conditions in older age severely limit the usefulness of any novel medication that might target the older population.
Historically women have been largely excluded from the major clinical trials, which has hampered the real usefulness of many medications that do not take into account the biological and cultural differences of women and members of the LGBT communities. The biological differences of women provoke pharmacokinetic and pharmacodynamic variations due to their smaller body size, higher fat and less water content, hormonal variations and varying levels of certain body enzymes. The fluctuating levels of hormones during the menstrual cycle and in pregnancy coupled by the metabolic changes when they use contraceptives must be considered when the effects of study drugs are being assessed by researchers. The particular mental and physical construction of gender and sexuality will influence the feminine lifetime experiences and health outcomes.
Minorities like Blacks and Hispanics have largely been under-represented in clinical trials due to absurd discriminatory guidelines that favored a certain segment of the population. The often-cited excuse that the “minorities do not sign up in good numbers” has been disqualified by the surging participation of them when they are properly, respectfully asked to participate in the clinical trials. Mechanically extrapolating all the scientific results obtained with a largely white middle class population can have disastrous consequences for the future treatment of grave chronic diseases. Three recent studies have highlighted that limitation in critical studies on Alzheimer’s Disease.
Dr. Melissa Murray has been the lead investigator in the seminal “Florida Autopsied Multiethnic” (FLAME) retrospective cohort study that examined the records of 1625 deceased Alzheimer’s Disease patients self-reporting as Hispanic/Latino (n=67) Blacks (n=19) and White Americans (n=1539) The investigators found that: “Hispanic decedents had a higher frequency of family history of cognitive impairment (58%), an earlier age of onset ( a median of 70 years).longer duration of the disease 9 a median of 12 years) and lower MMSE proximal to death 9 median of 4 points) Black decedents had a lower Braak Tangle stage ( stage V) and a higher frequency of coexisting hippocampal sclerosis (21%) compared to other groups.” The results seem to suggest that there are clinical differences that might affect the effectiveness of the treating medication.
Dr. Mungas et al. found that Hispanics and Black Americans were more likely than White Americans to have post-mortem neuropathological changes of Vascular Disease; they cautioned that the results must be evaluated with caution as only 67 Hispanics and 19 Blacks were included in this study, compared to 1539 White Americans. However, the suggestion that Vascular Disease may play a bigger co-morbid role in the evolution of AD in Minorities opens the door for the evaluation of opportune care and wellness interventions that would improve the health outcomes for these patients.
The growing use of blood biomarkers for the early detection of Alzheimer’s Disease—before the devastating clinical symptoms appear in a patient—has markedly changed the treatment schedules; the presence of apolipoprotein E4 (APOE4) have been shown to be the strongest genetic risk factor. Sid E. O’Bryant et al. analyzed the serum of 363 Mexican Americans (49 patients with AD and 314 normal controls) and found that AD patients had a lower concentration of APOE4 in blood. How could that be if the presence of that blood biomarker had been singled out as pathognomonic? Perhaps its presence, for still unknown reasons, is not clinically significant for the Mexican Americans. We should determine the biological risks for AD across a larger spectrum of different ethnic groups in order to design efficient therapies to control the disease. We still have much to learn.
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