Professor Catriona Waitt discusses the importance of access to research

Posted on: 28 September 2024 by Rebecca Derrick in LONGEVITY Blog

Access to information is an important consideration in various communities, but in the pharmaceutical research community, this idea needs to extend further to equitable access to research. Though not the only cause, a firm base of equal access to research is necessary in the work to eradicate global medical inequity.

What is the International Day for Universal Access to Information?

28 September was designated as International Day for Universal Access to Information by UNESCO at a UN level in 2019.

“UNESCO provides a platform and frame for all the stakeholders to participate in international discussions on policy access to information in the digital era as it empowers individuals, enables informed decision-making, fosters innovation, and promotes inclusivity and social progress.”

It may not be obvious why awareness formed from digital considerations would relate to a long-acting therapeutics team, but this concept is a foundational consideration for a vast element of the work we do.

Why is this day relevant to long-acting therapeutics research?

The Centre of Excellence for Long-acting Therapeutics (CELT) was formed by co-Directors Professor Andrew Owen and Professor Steve Rannard in 2020. One element of the broad set of activities we undertake, is to take existing medicines and work to create long-acting versions of them, seeking to reduce the drug burden associated with target diseases and create more convenient medical options for patients. One of our biggest projects is the LONGEVITY project funded by global health agency Unitaid. LONGEVITY is a consortium of partner organisations who cover the entire journey of concept, development, testing, licensing and clinical trials for long-acting drugs to prevent or treat malaria, tuberculosis and hepatitis C virus. At the foundation of LONGEVITY and other CELT activities is dissemination of information and new medicines to those in low- and middle- income countries (LMICs) who are most in need.

International Day for Universal Access to Information is all about making sure everyone can access the information they need to make informed decisions in their lives. Accessing thorough information about the medication a person takes is an important aspect of this idea. What is key within all CELT’s activities, is that there is equitable access to research outcomes and products. To build trust in the outcomes of our work, end users need to be represented in the activities that we undertake.

Earlier this year Professor Catriona Waitt presented a talk about the importance of equitable access to research in clinical work. While there is a lack of global majority participants in clinical trials there is a particular community whose safety must be specially considered, but are rarely allowed for. We asked Professor Waitt to write this guest blog for us as someone who saw the gap in this access and actively started work to change it.

What does Professor Catriona Waitt have to say about equitable access to research for pregnant and lactating women?

Almost everybody requires treatment with medication at some point in their lives. Whilst issuing a prescription may seem a routine task for many healthcare providers, for the patient this may be a time of anxiety. Everybody deserves access to the evidence they need to make an informed choice together with their healthcare provider, weighing up the potential benefits against any risks.

For some groups of individuals, this evidence is simply not available. Many diverse groups are negatively impacted by this situation, with women of childbearing potential being a key example. Worldwide, it is estimated that more than half of all women require some form of medication during pregnancy and breastfeeding [1]. However, in most situations, these women are systematically excluded from clinical trials, meaning that many drugs are used ‘off label’. I became acutely aware of this challenge in 2012 when I had my fourth child. My pregnancy had been complicated with about eight admissions in third trimester with persistent vomiting, malnutrition and opportunistic infections. After delivery I continued to vomit for another two years until I had surgery on my stomach to correct the underlying problem. Throughout this time, I was prescribed multiple medications and on each occasion, my first questions regarded the wellbeing of my baby. Mostly, I was given a vague answer, or told that I should be less anxious. When breastfeeding, I was similarly given little information and told that if I was concerned, I could simply stop breastfeeding. I found this situation unacceptable, disempowering and distressing. As soon as I was able, I began to systematically explore questions about medication transfer from mother to breastfed infant, with the desire to use my Clinical Pharmacology skills to challenge the status quo.

I was shocked by what I discovered. Having undertaken my PhD on tuberculosis mortality in Malawi, I was aware of the high rates of HIV in adolescent girls and young women. At that time, the World Health Organisation recommended that women living with HIV in low- and middle- income countries (LMIC) should exclusively breastfeed whilst taking antiretrovirals. In contrast, many high-income countries (HIC) prohibitively recommended against breastfeeding for these women with the threat of referral to child protection services should she be found to be breastfeeding (a situation which has thankfully changed in most places, as reflected in British, US and European guidelines). There were many unanswered questions [2], and few studies had systematically explored transfer of antiretrovirals from mother to breastfed child [3].

Whilst still on maternity leave, I wrote an Academy of Medical Sciences Starter Grant for Clinical Lecturers to develop and pilot the necessary techniques (clinical, laboratory [4] and pharmacokinetic) in Ugandan breastfeeding mothers-infant pairs. At the same time, dolutegravir was emerging as a likely ‘game changer’ for oral antiretroviral therapy, and with Professors Saye Khoo and Mohammed Lamorde, we gained funding from ViiV Healthcare to investigate the safety and pharmacokinetics of dolutegravir in women initiating antiretroviral therapy in the third trimester [5]. This was a very innovative approach – from the outset, ViiV Healthcare sought to understand understudied groups such as pregnant and lactating women and those requiring treatment for malaria [6] In addition, the company pledged to make the drug available in LMIC at generic cost within 18 months of licensing, a promise which was honoured.

These two pieces of work led to me relocating with my family to Uganda in 2014 to work at the Infectious Diseases Institute, Makerere University, and Uganda became our home from that time forward. I subsequently gained a Wellcome early postdoctoral fellowship to further explore the question of antiretrovirals in breastfeeding [7], then a Wellcome Clinical Research Career Development Fellowship to explore other drugs which were even more neglected: TB treatments [8], antimalarials [9] and antibiotics. Recently funded work will further build the repertoire of drugs studied, the pharmacokinetic modelling processes required and the stakeholder engagement necessary to transform policy and practice.

Over the past fifteen years there has been a change in attitude towards the ‘fair inclusion’ of pregnant and breastfeeding women in research [10,11], although we are still far from the point where pregnancy and lactation data are mandatory for all new drugs which are anticipated to be used in women of childbearing potential. It is interesting to note that there have been more pharmacokinetic studies of antiretrovirals in pregnancy than any other class of drug [12,13], and that in many aspects, the HIV research community has been at the forefront of shifting the mindset on the need for equity of access to research, and in moving from rhetoric to reality.

It is increasingly recognised that it is ethically essential that these studies are done in a timely manner [14-16], and that there is excellence in study design to ensure reliability of findings [17]. Community engagement and involvement is increasingly accepted as essential to ensuring that all elements of research, from protocol development through to results dissemination are accessible to those who will benefit most from them.

I was privileged to be part of a recent WHO working group drawing together an open access ‘toolkit’ drawing many of these aspects together with a specific focus on antiretrovirals; the principles can easily be adapted to other therapeutic areas. The change in mindset is apparent in several recent clinical trials protocols: the ongoing ILANA trial has set recruitment caps to ensure recruitment of 50% women, 50% ethnically diverse people and 30% over 50 years of age to include a more representative study population than reflected in previous trials of long-acting cabotegravir and rilpivirine [18]. In the recently published PURPOSE 1 clinical trial, contraception was not required and participants who became pregnant could choose to remain in the trial and continue the medicine, lenacapavir, after a new informed consent process reviewing risks and benefits. 510 pregnancies were reported, 277 of which were completed at the time of publication with no safety concerns being raised [19]. These protocols reflect best practice and should be celebrated as exemplars.

However, there remains much to be done to ensure continued equity of access not just to research and the emerging data, but also to novel therapeutic agents. In partnership with multiple global stakeholders including CELT, Venter and colleagues, have recently given an eloquent, but disheartening overview of the challenges in affordable, equitable access to long-acting injectable antiretroviral drugs [20], despite clinical trials in LMIC settings demonstrating proven benefit [21]. These delays are unacceptable, especially in the light of established global HIV targets.

In other clinical areas, and for complex and understudied populations including pregnant and breastfeeding women and their infants, and also children and adolescents, those with severe intercurrent illness and polypharmacy, those with hepatic or renal impairment, or the elderly, there remain enormous gaps in availability of specific evidence to inform discussions of risks and benefits and enable clear decision making by patient and healthcare provider. I believe it is important that we break down silos between disease areas, between industry and academia and between researchers and the community as we harness all of our strength to address these major challenges.

It is unacceptable that anybody lacks access to the information they need about their medication. As a community of diverse individuals, we will not rest until remaining barriers are dismantled and equity becomes reality.

The LONGEVITY project aims to simplify TB, malaria and hepatitis c virus treatment and preventative treatment to reduce the drug burden and the number of patients requiring complex therapies for active disease.

Find out more about the LONGEVITY project

The LONGEVITY Project is funded by global health agency Unitaid

The project also involves critical partners and collaborators in the Clinton Health Access Initiative, Johns Hopkins University, Medicines Patent Pool, Tandem Nano Ltd., Treatment Action Group and the University of Nebraska Medical Center