1.What is a Diversity Plan?
In order to know if a new drug or medical device works in specific patient population, we need to have data generated from clinical research. This is why ‘clinical trials diversity’ is not just another political expression. Proper representation of clinical trials participants is an important part of clinical research, and it is the focus of many regulators.
In Nov 2023, 21 of the 84 UK Research Ethics Committees participated in debate regarding underrepresentation of different groups in clinical research. They all agree that more should be done to include underrepresented groups.
While there is a requirement for diversity planning in the USA, there are no official requirements in the UK and EU. The UK regulators are currently developing diversity plan and there is no doubt that EU will follow the same approach.
2. Why do we need a diversity plan?
While we all like to embrace equality the reality is that people are different, and they respond to treatment differently. It is important to remember that people even experience diseases differently. What works in European patient population will not necessarily work in the Asian patient population. However, an analysis of 230 oncology clinical trials conducted in 2019 (totalling 112,293 participants between 2008 and 2018) found that 37% of studies did not report race. Often there is minimal information collected from the participants and this is due to various reasons – data protection laws, information not considered relevant, etc.
3.What are the main challenges in clinical trials diversity?
3.1 Trust in regulatory agencies
The trust in regulatory agencies is important part in involving participants in clinical trials. A survey results from 2,021 participants published in Mar 2023 shows that 23% of them do not trust USA FDA. The survey also found that those who live in rural areas have less trust in FDA than the urban areas.
FDA is not the only agency that suffers from trust issues. The inevitable perception that the regulators are connected to the big business and having members who come from the corporate world does not help them in the eyes of the general public. Another example is the way COVID-19 vaccines were approved promptly in comparison to all other drugs caused uneasiness in some people and even feeling that they were not assessed properly.
Regulatory agencies have to find their way to assure concerned people that they are trustworthy and reliable.
3.2 Language barriers
Some patients are excluded from research because they don’t speak the language of the country where they live in. For example, in the UK researchers are encouraged to provide translated versions of the informed consent but in some countries, like Germany, it is a regulatory limitation that exclude those who don’t speak the language.
If we want more patients to participate in clinical research we have to consider the language barrier and provide them materials in their native language wherever possible.
3.3 Heavy use of technology
The use of technology could discourage older participants from taking part in research because they may feel uncomfortable with using devices, mobile apps and other technologies.
This is, however, not a limitation only to the older population – there are young people who also try to avoid devices and apps due to data privacy concerns.
It is important when designing the clinical trial to consider these factors.
3.4 Inclusion criteria restrictions
It is very common to see restrictions in the eligibility criteria related to age and pregnancy. In some cases, these restrictions are reasonable but in others – they are not. Often companies try to avoid older population because of concerns of comorbidities and disease burden, but it is important to remember that the study population has to be representative of the actual patient population affected by the disease.
Another often excluded group are patients with hepatitis or HIV. In cases where the study drug could interact with their therapy, it is justified to exclude these patients. However, for those who don’t have active hepatitis or are on long term HIV therapy and stable, it may not be appropriate to exclude them.
A very good example of how the restrictions of the clinical trial protocols could affect participation is a condition called benign ethnic neutropenia, which is observed in patients with African ancestry. The neutropenia in this case is not associated with increased risk of infections, however many studies have very strict protocols when it comes to neutrophil count. This could exclude patients with such genetic condition.
Recently FDA issued a guidance recommending the eligibility criteria in oncology clinical trials to be more relaxed in terms of mobility status, required lab parameters and disease burden. Hopefully this will be reflected in upcoming studies.
4. What to consider when developing diversity plan?
4.1 Collecting the correct information
As a first step the companies have to consider collecting information on race, ethnicity, sex and age. As strange as may sound not all studies collect this information. Maybe there are a lot of different people participating in research but since the data is not collected, we don’t know about it.
4.2 Selecting hospitals which have the patient population
Selecting sites which have the patient population is another important step in reaching out to more potential participants. Here we have to find the good balance between site experience and patient population as not all sites which have the patients will have the relevant experience.
4.3 Increasing the awareness of clinical research among physicians
Often the issue is that physicians do not refer patients to clinical trials. This could be due to lack of knowledge that the study exists or lack of time. Reaching out to all relevant professionals is an important step of bringing awareness of the study. Another critical step is finding an easy way to refer patients to clinical trials.
4.4 Creating patient-friendly clinical trials
The design of the study should consider how to make it convenient for participants to attend visits and to maintain overall compliance. The companies also need to think about reducing the overall burden of the clinical trials wherever it is possible. Sometimes there are limitations due to regulatory requirements for data collection.
The decentralisation is another approach to offer more flexibility in clinical trials and give options to patients to attend their local physician or a nurse to attend at their home.
Another point is that participants could be reimbursed for their travel expenses to help those with low socioeconomic status to take part in research. While this may not be seen as critical it could be a major barrier for some patients to participate in research.
Real world evidence studies (RWE) may offer opportunity to include in clinical research minority groups that otherwise may not be interested to participate. RWE provide great opportunity for already approved drugs and medical devices that need post-market surveillance.
4.5 Patients engagement and training
In order to recruit participants from different backgrounds the companies have to try to work with patient groups and provide disease area training and materials in local language to potential participants to help them improve their understanding of clinical research. While this may not be an attractive option for many companies, it will be very beneficial for their long-term reputation in the communities and brand awareness.
Patient engagement and training should not only be limited to the companies which conduct research but the regulatory agencies, charities and other parties also need to be involved in bringing awareness of clinical research.
5. Is there a short cut?
Now if you wonder if you can set up your studies in the developing countries and meet the diversity requirements, you need to take some points into consideration. Patients from developing countries could have poorer health because of different standard of care and living standards and this could affect the overall safety profile of the product.
Another complexity is that health status of someone who lives in a developing country and a person from the same ethnic background living in a developed country could be quite different.
As addition many regulatory agencies would like to see data from their region as part of marketing authorisation. For example, China, USA and EU are known to expect to see data representative of their population. If you present them data from developing countries this data will likely not be accepted.
Literature
- Who distrusts the FDA? Survey shows gender, location and politics are key factors
- REC shared ethical debate
- Diversity in clinical trials in Europe and the USA: a review of a pharmaceutical company’s data collection, reporting, and interpretation of race and ethnicity
- Increasing the diversity of people taking part in research
- Diversity and Inclusion in Clinical Trials
- Diversity Plans to Improve Enrollment of Participants from Underrepresented Racial and Ethnic Populations in Clinical Trials Guidance for Industry
Published: 28 Oct 2024