Human Alzheimer's DNA Vaccine(Institute for Molecular Medicine Finland)

An experimental Alzheimer’s vaccine that stimulates the immune system to remove forms of amyloid proteins that accumulate in blood vessels appeared safe in a study of patients with mild cognitive impairment or mild Alzheimer’s disease. People in the Phase II, 134 patient study were assessed a year after they received the first of 6 shots. When measured on a common test for cognitive impairment called the Mini-Mental State Examination (MMSE), their disease slowed by a maximum of 38% in people who got the vaccines compared to placebo. That result was statistically significant. But a later review at 18 months and 24 months, which showed an 18% slowing of disease, was not.

The burden of diseases does not discriminate, and different populations may react very differently to treatments. To properly test drug efficacy across patient populations, diverse participants need to have access to and the opportunity to participate in clinical trials. Yet, despite the emphasis on recruiting more diverse participants, recent data shows a concerning trend – clinical trials have somehow been less inclusive than in decades past and the inclusion of Black participants in clinical trials fell by 46% in the past four years. This raises the question of whether efforts to promote diversity in clinical trials are genuinely advancing or merely superficial actions taken by pharmaceutical companies to pay lip service to increasing regulatory pressure. Diversity remains low in clinical trials While diversity may be flagged as a priority, racial and ethnic minorities continue to be left out of clinical trials, as do members of the LGBTQIA+ community, older adults, pregnant and lactating individuals, and people with disabilities. Recent studies continue to highlight this lack of diversity in clinical trials. A 2022 report from the Committee on Improving Representation of Women and Underrepresented Minorities in Clinical Trials and Research shows that lack of representation continues to be a “critical shortcoming” in clinical trials conducted in the U.S. Specifically, the committee found only a small decrease in the total percentage of White participants in clinical trials from 2014 (84%) to 2020 (74%). And, upon further investigation, it was discovered that this wasn’t even attributable to improved diversity within trials, but rather to the inclusion of new international data. In another example, despite its international scope, a trial for an Alzheimer’s drug by Roche’s Genentech unit featured 97.5% White patients and only 2.8% Hispanic, even though Hispanics are one and a half times more likely to be diagnosed with the disease. Yet another study recently published in PLOS further explores the ramifications of non-representative clinical trials, stating, “Medications and interventions are routinely tested for safety, but with low inclusion of racial and ethnic minorities in clinical trials, safety data could be lacking for racial and ethnic minorities. Additionally, exclusion of racial and ethnic minorities in clinical trials may exacerbate health disparities due to potential differences in treatment efficacy, dosing, or patient comfort and trust in a novel medication.” When diverse trials are successfully conducted, the impact can not be disputed. In the April 2023 issue of The New England Journal of Medicine, researchers discuss a recent experiment: “Investigators randomly provided patients with hypertension with results from one of two trials of a new hypertension drug. Both trials showed that the medication was effective at lowering blood pressure. In one trial, 15% of participants were Black; in the other trial, less than 1% were Black. Giving patients the results from the more representative trial increased by 20 percentage points the likelihood of Black patients’ believing that the drug would be as effective for them as it was for the trial participants, without altering white patients’ perceptions of the drug’s effectiveness.” This study clearly shows that the interest and confidence in new treatments that diverse patients have, significantly increase with inclusive clinical trials. Having diverse representation in clinical trials is therefore critical to ensure that healthcare interventions are considered to be effective, available, and safe for all patients. Efforts are underway to finally hold pharma companies legally accountable for running clinical trials that better reflect the demographic distribution of the U.S., including a new law requiring diversity action plans to be included with clinical submissions to the FDA. The onus is on pharma companies to evolve their clinical design and recruitment processes ASAP. Looking beyond demographics The healthcare industry is sitting on a wealth of data gathered from electronic health records, commercial pharmacies, health systems and payers, and health tech companies. So much that it makes up one-third of the world’s data. Pharmaceutical companies need to tap into this type of data to build inclusive clinical trials, focusing on participant recruitment, site selection, and developing diversity plans that adhere to the newest FDA requirements. With a plethora of data out there, pharma companies need to figure out which is most significant and how it can most effectively be used to improve clinical trial diversity. The first step is ensuring only the best available data is being used to identify diverse patients. While factors like age, gender, and ethnicity are important and easy to collect in certain locations, this census-level data does not provide a meaningful enough understanding of what’s happening at the disease and patient levels. Social determinants of health (i.e., affordable housing, access to education, public safety, availability of healthy foods) are certainly other valuable components to factor into site selection strategies, however, finding this data is often challenging and still does not provide a complete picture. Pharma companies need to go beyond patient demographics and social determinants of health to access granular patient insights on the disease level. For example, let’s say that a clinical operations team is planning a trial in the state of Georgia for breast cancer treatment. If they have the ability to identify exactly what percentage of breast cancer patients are Black in that state, then that can be used as a representative diversity benchmark and can act as a recruitment goal. With access to patient diversity data this granular – all the way down to the indication level – the data can be analyzed and meaningful insights can be pulled from it. These findings can improve clinical trial design and execution to promote diversity and inclusion. Having access to just this granular data alone will not fix the problem, however. Addressing the core issues that keep diverse patients out of trials, in combination with the right way of applying that data, is the key to diversity success. The ABCDs of clinical trial diversity gaps The main causes that keep diverse patients out of trials can be broken down into what I call the “ABCD” factors: awareness, burden, confidence, and disqualification. Awareness of trial participation, and more importantly, the lack of it, is a huge barrier. According to a study by Deloitte, 80% of patients might be interested in participating in a study but have never been asked to do so, nor do they know where to find relevant information. The burden of trial participation is one of the main reasons patients refuse to participate or drop out early during the study. Time away from work or home, in combination with the time and cost to travel to sites, is a luxury many patients can’t afford. Confidence in clinical trials, and the pharma industry in general, is low due to the lack of transparency in data sharing and the many mistakes the industry has made in the past. Patients often still compare trial participation with being a guinea pig for a large corporation. Disqualification from participation is another reason why clinical trials are not more diverse. This is often unintentional due to stringent inclusion and exclusion criteria of the trial design to measure the effect of the treatment on “the ideal patient.” Diverse patients often suffer from other underlying conditions due to genetic predisposition which exclude them from participating. Once we acknowledge these “ABCD” barriers that are preventing diverse patients from participating in clinical trials, we can then leverage granular data to determine where improvements can be made. For example, the following insights can help clinical feasibility teams design more inclusive trials and develop a diversity plan according to the latest FDA guidelines: Using patient demographics to uncover diversity gaps in current clinical trials and identifying any specific health conditions that prevail within diverse patient populations. Understanding who the investigators are and comparing their profiles against target patient populations to build a pool of diverse staff. According to a study by the Pharmaceutical Research and Manufacturers of America (PhRMA) and the Deloitte Center for Health Solutions (CHS), “Racially and ethnically diverse investigators and staff who reflect the communities they serve are key community ambassadors for clinical trials and can help ensure trials are culturally competent and mindful of unconscious/implicit bias.” Analyzing sites to understand the impact of research taking place and their experience, capacity, and interest in supporting diverse clinical trials. It’s important to seek locations where diverse participants already receive care and consider non-traditional sites such as community health centers or pharmacies. Improving representation in clinical trials is a big undertaking. It will not be solved overnight and it requires a strong commitment by all stakeholders within the healthcare lifecycle. Granular, indication-level data can help clinical operations teams design more diverse clinical trials that reflect the patient populations they serve. And ideally, more diverse trials will bring more effective treatments and more equitable healthcare.