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Mistrust in medical research: a patient perspective

January 22, 2021 | #COVID19, Patient-centricity, clinical trials, coronavirus, patient, patient engagement

The recent development of several COVID-19 vaccines has placed medical research firmly in the spotlight, highlighting public confusion and misinformation about clinical trials. Patient advocate, Trishna Bharadia reveals what the life sciences industry can do to rebuild trust.

In medical research, trust has traditionally been hard-fought for. Terms like “lab rats” and “guinea pigs” are often used in conversations about clinical trials. For some communities, the historic unethical treatment of participants is also still a raw memory^[1]. People tend to remember when things go wrong, and this casts doubt over procedures and leads to questions about whether we can really trust industry, scientists, and researchers.

The approval and roll out of the COVID-19 vaccines have put the spotlight on clinical trials. I have never known the subject of clinical trials to be as discussed as much as it is right now. The subject is being discussed everywhere – in the mass media, on social media, in dinner conversations, and in discussions with friends.

It’s Thalidomide all over again

It’s not just patients – it’s the fit and healthy public who, until now, might have never thought about how long it takes to approve an intervention. They are asking: what are the ingredients? How many people participated in a trial? What were the adverse events? And how long did the trial last? Equally, to truly get a handle on a pandemic, never before has it been as important for patients and the public to have trust in the process.

“I’m not an anti-vaxxer, but…..” is a phrase I’ve seen repeatedly on social media over the past few weeks, especially when the news broke of the Medicines and Health Products Regulatory Agency’s speedy approval of the Pfizer-BioNTech COVID-19 vaccine in the UK. Suddenly people were comparing the length of approval processes in the UK, Europe, and the US. “Corners have been cut,” “The vaccine contains fetuses,” “It’s Thalidomide all over again”, all demonstrate a lack of public knowledge and awareness about how trials are conducted in the present day. So, how can we improve patient and public trust in the clinical trials process?

Stop hiding from the mistakes of the past

The Thalidomide Society has said that comparisons between thalidomide and the COVID-19 vaccine are “insulting”^[2]. In the US, people often use the Tuskegee Study^[3] and the case of Henrietta Lacks^[4] to demonstrate why people should not trust medical research. However, what is usually left out is how those cases changed the way research is conducted.

Thalidomide was marketed during the late-1950s and early-1960s in the UK and was later found to cause birth defects in unborn babies. Dr. Ruth Blue, Consultant for the Thalidomide Society, highlights that whilst the morning sickness drug initially passed animal safety tests, it was never properly tested on humans. Its sale was never approved in the US because the FDA did not think sufficient testing had taken place. She concludes that Thalidomide completely changed the way medicines are tested and approved^[5]. Examples like this should be used to reassure people that things are done differently now and to raise awareness of how regulations and standards are evolving.

Increase awareness and understanding

The Good Clinical Trials Collaborative (GCTC), for which I’m a member of the Writing Group, is a global initiative that recognizes that randomized clinical trials are currently governed by a complex system of guidelines and regulations that are outdated and confusing. These complicated rules have led to an over-interpretation of the guidelines and higher costs for trials because of failure, delays, and wastage^[6]. However, the general public is unaware of how such guidelines are developed, why they’re needed, or why they should be adapted.

We need more awareness about how interventions are made and how they work, not just for COVID-related interventions but for all. It’s worrying how many people still refuse the flu vaccine because they believe “it gives them the flu.”

The healthcare and life science sectors have the opportunity to promote and publicize such initiatives widely, so everyone can understand how researchers are being guided in their work and how trials are conducted. Doing so will not only inform the general population, but it will also reassure patients, in turn improving clinical trial recruitment

I didn’t realize everything needed to be tested

Education about clinical trials, how they’re conducted, and the regulatory approval process is greatly needed. The pandemic has highlighted an urgent need for this, but it’s been an issue for a long time. A brilliant video from the Center for Information and Study on Clinical Research Participation (CISCRP), Sanofi and Langland, – The MT Pharmacy^[7] – shows what our world would be like without clinical trials.

One ‘customer’ in the pharmacy says, “I didn’t realize everything needed to be tested.” In that case, we can’t then expect people to know what the testing process involves. More public awareness initiatives, such as the European Medicines Agency’s recent public stakeholders meeting on the scientific evaluation of the COVID-19 vaccine^[8] will help to better inform the public of how medicines go from the laboratory to the market. In the meeting, they provided a transparent view of the drug development process, including why it usually takes so long to conduct a trial, how is long-term safety data gathered, and how the approval process works.

Educate against fake news

The rise of social media and internet blogs has given us all the tools to easily self-publish content, leading to an environment where click-bait headlines prevail, and individuals are not held accountable for publishing incorrect information.

Fake news can have a dire impact on the uptake of therapies and lead to mistrust in healthcare. Members of the public need to understand which sources are trusted and which are not. This includes educating people about different stages of clinical trials, their purpose, and how to recognize robust data.

People need to be able to put things into context and read beyond the headlines. A good example is a recent incident in the UK that made headline news, where two NHS workers who were among the first to receive the Pfizer/BioNtech vaccine suffered allergic reactions.

The news sparked some panic among patients on social media. However, delving beneath the headlines, we learned that people with a history of severe allergic reactions were excluded from the clinical trial protocol, so it’s unsurprising that we will see some cases as the vaccine rolls out.

Within the trial itself, there was a low rate of allergic reactions among the 18,000 participants^[9]. The two people in question already had a history of allergic reactions because they carried Epi-pens. Those with a history of strong allergic reactions should always speak to their doctors before getting the vaccine. However, allergic reactions can occur with many vaccines, so it is not as much of a red flag as some of the headlines alluded to. If it had been any other vaccine or drug, would it have even been headline news at all?

Create transparency and clarity

Educating the public goes hand in hand with ensuring transparency and clarity. Unclear and incomplete information fosters distrust. For example, the public unease about the lack of available information around Pfizer’s legal indemnity agreement with the UK government for its COVID-19 vaccines and the company’s refusal to offer any details^[10].

Even for me, someone who is very knowledgeable about the industry, highly health literate, and very well-informed, this hasn’t sat well. Providing the public with more opportunities to engage with industry professionals would perhaps help with this. The Royal Society of Medicine has been running a series of COVID-19 webinars. Whilst they are “forhealth professionals, by health professionals^[11]” I’ve been watching them as a non-HCP and have found them extremely useful, especially as it provides an opportunity to be able to ask questions directly to the experts.*

A patient-centric trial design has the knock-on effect of increased recruitment and retention, which can lead to greater diversity and efficiency

Information that is made available in plain language, digestible lengths, and expanding open access to research papers will help improve healthcare literacy. Under new EU regulations, sponsors will be required to provide a lay summary of clinical trial results^[12]. Outside of this, there is also an opportunity for creating lay summaries of other types of publications, including manuscripts, conference abstracts, and posters. With the increased spread of fake news, information from healthcare companies is rising in credibility^[13], so sponsors should recognize the importance of providing this information in an understandable and easy-to-process format – not just because they have to, but because it will be beneficial to the industry to have a more informed population^[14].

Partner with patients and the public

Improving patient and public involvement (PPI) in clinical trials is another key area that could help to increase trust in the process. Treating patients as activated and valued partners, rather than passive subjects, can increase the success of a trial by making it more relevant and appropriate. The patient will also feel like a partner, improve their perception of a trial.

A patient-centric trial design has the knock-on effect of increased recruitment and retention, which can lead to greater diversity and efficiency. Overall, the process becomes more relevant to a 21^st-century diverse population, something that has been recognized by the FDA, which has recently published new guidance for enhancing diversity in clinical trials^[15].

In fact, Moderna slowed down recruitment for its COVID-19 vaccine trial specifically to address a shortfall in recruitment from ethnically diverse populations for an illness that has been shown to disproportionately affect people from certain ethnic groups^[16].

Unfortunately, PPI has not become such an embedded part of clinical trials and it is not seen as indispensable yet. I’ve heard many industry professionals talk about how the speed at which the COVID-19 situation evolved meant that PPI was pushed to one side, indicating that it’s still considered a “nice to have” rather than an essential part of the process. This needs to change. Patients and the public represent a key group that can help the industry build trust within the wider population, so we need to make the most of this.

Increasing public and patient trust in clinical trials and medical research is a complex issue and one that will not be solved in a single strike. It will require sustained and coordinated efforts from stakeholders everywhere, not just while the time is ripe, but for many years to come. Communication in general and scientific communication specifically in the time of a public health emergency can be extremely powerful. It can make or break the public’s buy-in when it comes to accepting interventions.

*Fishawack Health does not advocate that patients use materials designed for healthcare professionals.