We are all different, aren’t we? Indeed, and in this lies the beauty!
No doubt that the way we grow up influences who we are in the sense that how and where we live, learn, work, and play as well as if we have access to high-quality healthcare, food, and education can also influence our health outcomes in general.
Similarly, negative experiences and exposures, such as pollution, disease, and discrimination, can negatively affect our health. Therefore, our health status reflects the outcome of the effects of numerous factors.
So people may experience the same disease differently. This is because it is determined by the many factors previously mentioned that can influence the risk and likelihood of developing a disease, experiencing a long-term health outcome, and responding to treatment including (but not limited to): age, gender, presence of comorbidities, genetic variation and geographic ancestry as well as life experiences (negatives, such as psychosocial stress and lack of basic resources, or positives, such as educational and employment opportunities), unhealthy behaviors (e.g., substance use, sedentary lifestyle, overeating, risky sexual activity) and to the opposing side: health-promoting behaviors (e.g., adequate sleep, obtaining recommended preventive services, physical activity, healthy eating) can also contribute.
Furthermore in the same sense, different people may have different reactions to the same medicine based on their age, gender, weight, race, ethnicity and other factors.
An individual’s Socioeconomic Status could be a major predictor of health outcomes, because it can impact many aspects of life like access to healthcare and prescription medications or nutritious foods and other resources for healthy living.
But the question lies here: do these Socioeconomic Status measures (i.e., education and income level) get collected routinely and reported in clinical trials?
Utopia for healthcare would be developing novel cutting-edge therapies within a diverse patient population. Those in Pharma know why I called this a utopia and know that it has always been a challenge for the biotech/pharma industry. Commercial colleagues of the industry are pulled back by the increased cost of bringing new therapeutics to market while medical affairs see an additional pressure to conduct clinical trials that mirror the diverse population which just multiplies the challenges that the industry hasn’t quite found the answers to.
In simple terms, to be able to do this, we need to know if the developed medication works for everyone.
Historically, clinical trials relied almost exclusively on white male participants and did not recruit actual participants who were most affected by a particular disease, or condition.
This act has had its toll on our understanding of diseases and conditions, preventive factors, and treatment effectiveness across different populations – slowing it a lot.
Unfortunately, disparities do exist when testing new drugs, therapies, and devices. Among the many reasons for this, lack of diversity in clinical trials ranks near the top. This applies to race, age, gender, socioeconomic status, and even disease state. An evident example of this is the elderly population who are constantly excluded from clinical trials, for somewhat scientifically valid reasons, yet you can argue against that because not only are they a very large and the fastest growing portion of our ageing planet’s population but they also make up the biggest share of patients for particular health conditions. The list goes on where historically enrolment preferred men over women, white over individuals of colour as well as patients with one disease rather than “realistic” patients with comorbidities – say, someone who is HIV positive and also diagnosed with cancer – typically is not eligible to participate.
The dark side of this disparity off course also lies in the hands of biotech and pharmaceutical companies who design their clinical trials based on what will get their drugs approved and on the market as quickly, safely, and cost effectively as possible. It makes sense if you put yourself in their shoes because if more participants are eligible – you have a higher probability of potential risk, adverse events, and ambiguous data — drug developers sacrifice not only time and money, but the potential success of their drug.
In clinical research, when scientists combine information from individual research participants, this is called data aggregation. This step is particularly an important part of the research process that protects the anonymity of research volunteers and strengthens the statistical analysis of the study. As much as this is an integral part of data collection and reporting of the all the trial inputs, it could be a double-weapon serving to unmask hidden truths like for example, aggregation of demographic data, including race and ethnicity, covering up important differences in health risks or outcomes for specific subpopulations.
For example, many prior studies on the health of Asian Americans have not always examined differences by nationality. A recent study found that among Filipino, Vietnamese, Chinese, Japanese, and Korean American adults living in California, categorizing all participants as ”Asian American” masked at least one health disparity for each subpopulation.
Was this only historically, so what about now?
The numbers still tell the story: According to Food and Drug Administration data, in 2020 75% of trial participants were white, 11% were Hispanic, 8% were Black, and 6% were Asian.
A majority of global clinical trials fail to enroll enough patients over 65, patients with disabilities, and patients of color for a variety of reasons the main ones being that clinical trials aren’t easily accessible to many patients as well as not trusting that these trials serve their best interests.
In return, these gaps in knowledge have created pitfalls in the quality of health care decision-making mainly as well as the ability of healthcare systems to counsel people on ways to reduce their risk, optimal treatment responses, and even the development of more effective medications or interventions. Therefore, it’s essential that clinical trials include people with a variety of lived experiences and living conditions as mentioned above, as well as basic characteristics like race and ethnicity, age, and sex, so that all communities can benefit from scientific advances.
If a clinical trial doesn’t include appropriate representation of diverse patients, the results and findings cannot be translated broadly across all patient demographics. You’ve probably heard during your practice: “this doesn’t apply to our patients” – well, as sarcastic as that was a couple of years ago, regulators have started to set clear expectations for clinical trial diversity to reflect their distinctive populations.
Clinicians and researchers should carefully consider the inclusion or exclusion criteria for their clinical trials. Since many of the baseline characteristics are intertwined like trials which exclude specific participants with high blood pressure or other comorbidities for example may end up excluding many patients over 65 years old, who are more likely to have the condition in scope of the trial. Also, when individuals choose to participate in a clinical trial, they will represent people like themselves and from their local communities — in age, race, ethnicity, and gender.
To simplify the magnitude of this problem, this makes these specific populations underrepresented in the trial population and hence make the results less applicable to this group who may have otherwise benefited the most from its findings if included. The list goes on with disparities like postmenopausal osteoporotic women living in big cities and asthma participants living in at high elevations.
Therefore, it is integral to advance our understanding of new treatments, that the trial participants done on it reflect the disease epidemiology and represent clinically relevant populations. This is because the safety and efficacy of these treatments can differ based on age, ethnicity, gender, race and sex.
All the clinical research efforts would go astray if we do not do a good job in evaluating and ensuring a study population that would, upon extrapolation to the population as a whole, be representative. This is an integral part in bringing a new therapy to market because not only are we all biologically and genetically different from one another but also because certain minority patients may very well benefit from early access to therapies, potentially prolonging or saving their lives. In light of this, it is crucial to test new therapies in diverse populations to firmly conclude whether a drug is safe and works.
It was good to see that the FDA recognizes this issue as it released a draft guidance in June 2019, Enhancing the Diversity of Clinical Trial Populations – Eligibility Criteria, Enrollment Practices, and Trial Designs. This draft guidance is a step in the right direction and has some interesting thoughts and potential solutions for the industry to implement.
Additionally, in 2017, NIH updated its policy on the inclusion of women and people from racial and ethnic minority populations with a requirement that “recipients conducting applicable NIH-defined Phase III clinical trials ensure results of valid analyses by sex/gender, race, and/or ethnicity are submitted to Clinicaltrials.gov.”
Further recommended reading on this topic can be found in The National Institutes of Health Minority Health and Health Disparities Strategic Plan 2021-2025 was developed by NIMHD, in collaboration with all the NIH Institutes, to outline NIH’s commitment to improving minority health and reducing health disparities. It outlines an ultimate goal to increase the overall proportion of participants from diverse populations included in NIH-funded clinical research to 40% by 2030 and within specific major disease categories.
Below are my personal views on some tangible actions we, as an industry, can take to increase diversity in clinical trials:
- Widen eligibility criteria
Easier said than done. Companies must incorporate wider eligibility criteria earlier in the drug development process. Drug developers must be thinking about this in Phase 1, not Phase 3. I understand this is not an easy ask for smaller companies, which have less resources and capital on hand. A majority of companies need to achieve proof of concept and securing investor interest as a top priority in early stages of development, making it difficult for them to allocate time, resources, and funds toward inclusive clinical trial design.
- Tap into “Non-Academia” medical centers
A majority of clinical trials often take place in large research and academic facilities located in Europe and North America, due mainly to their academic credentials and experience, yet many “realistic” patients needing care actually live in rural areas.
Therefore, tapping into the “non-academia” based medical centers and community clinics can surely help. They may not have “the” big name affiliation or “the” most published studies, but what they do have is accessibility to a generous pool of patients and a keen understanding of their local community. Regions I usually highlight and see potential: Africa, The Middle East as well as Central Asia; centers in these areas if managed correctly can often be your trial’s biggest recruiter.
- Make use of the digital age
A big barrier for many patients is the financial burden and time commitment necessary to travel regularly to doctors’ visits. Clinical trials require participants to visit the doctor’s office weekly or mandate a number of assessments in order for the patient to be considered compliant with the protocol – this is particularly burdensome for elderly and low-income individuals. In the gulf, for example, as well as parts of North America, there is an insurance copay that is not covered by the clinical trial sponsor company; this cost to participate is a hurdle to optimum patient participation. Because most pharma companies are racing to be “patient-centric”, this is a golden chance to implement aspects of virtual clinical trials, using technology and other home-based and telemedicine technologies to enable the expansion of clinical trials into underrepresented areas and also reduce the obstacles of distance, costs, and availability. The future could also see us using AI in creating modeled “pseudo” clinical trials.
- Listen to your patients
Before the development phase trials, not after commercialization of the product, listening to patients and their unmet needs, perhaps through patient advocacy groups and incorporating their aspects in the design and conduction of the trials as well as getting their insights on the development phase steps all the way to commercialization is essential. From my experience as a Patient Advocacy Manager during the period of 2016 till 2018, these meaningful relationships with advocacy groups take a long time to foster, yet once they are in place, the scientific reward is priceless.Researchers should also design their studies and provide resources to make it easier for people with lower socioeconomic standards to participate in clinical trials, such as offering convenient locations and hours of operation, childcare services, and transportation vouchers.
- Support diversity-focused public policy
In certain countries, maintaining diversity in clinical trials is written into the law. And while this isn’t mandated in the United States, it is certainly a measure for consideration. Pharma is already over-regulated in many aspects and more rules would not benefit anyone. A potential solution to enable this would be for the FDA and other regulatory authorities to institute a diversity program similar to the pediatric and/or orphan programs that already exist to assist these niche populations. This would provide monetary benefits that incentivize trial sponsors to include diverse populations in their clinical trials.
- Make diversity and inclusion a mindset
At the end of the day, true change in clinical practices won’t happen unless diversity is prioritized within an organization — and from the top down. A company’s executives and clinical leads must be vocal and action-oriented about their commitment to ensure diverse representation at every phase of development.
In closing, the provocative questions remain: What’s the point of developing therapies for patients if we exclude groups of individuals who may benefit from them and provide more robust data for all patient populations? Why do we worry more about the statistical difference between two arms in a clinical trial than whether the trial as a whole represents the community we serve? We must be better about servicing all populations, not just those that are easiest to access; this will bring us a step closer to biopharmaceutical companies’ ultimate goal: improving the health of all people.
In simple terms, the aim is to have clinical trials that are as representative and accessible as possible, as well as reflect patient populations experiencing the disease and intervention we are studying across age, ethnicity, gender, race and sex.
There have been efforts in countering mistrust in clinical research, which have given rise to us seeing people from racial and ethnic minority communities being more willing to be represented in clinical research. This trust is better fostered when members of these communities have their inputs considered by researchers when carrying out research.
It is evident that enhancing the diversity of clinical trial participants is a critical step towards combatting healthcare disparities and enabling health equity in general. Participation in clinical trials by people of all backgrounds can make a difference by reducing health disparities among underrepresented populations and improving the development of medicines for everyone. This diversity should be ensured by recruitment processes that continue to evolve so that clinical trials achieve that objective and therefore help safely bring new medicines to all people.
In the end, as an industry that includes groups of researchers dedicating their lives to improving the health of others, regardless of their race, age, gender, or disease, we know that empowered patients and their families are better prepared to make informed choices about their health care and about participating in clinical trials. The question now is how can we do better?
About the author:
Shereef Ibrahim, MBA
Currently an MEA Medical Manager, Shereef previously spent his 15 years of experience at Novartis and Amgen in different medical roles of varying responsibilities covering 10 therapy areas across the Middle East & Africa region constituting nearly 24% of the world population.
Shereef worked as an MSL for Bone & Pain, Respiratory and Transplantation in Egypt during the period of 2014-2016 which added a lot to his prospective of being patient-centric in business.
Highly energetic, award-winning, purpose-driven pharmacist with a passion for patients: who prides himself on empowering medical affairs teams of leading global pharmaceutical companies to effectively use data in communicating scientific and clinical information to the medical community through various channels by enabling them to develop and execute effective medical affairs strategies.
His career in Medical Affairs to date has provided him with invaluable knowledge, driving country’s medical affairs strategy in line with the global strategy and quoting him: “I was lucky enough to have assisted thousands of HCPs find the right management solutions for their patients”.