Does a clinical trials sponsor or their CRO need to provide study staff and subjects Personal Protective Equipment (PPE)? Do “civil society” groups have rights to govern a clinical trial? Vexing questions are surfacing in what is becoming a charged COVID-19 vaccine clinical trial in South Africa. On one side is the study sponsor, a South African contract research organization (CRO) called TASK Applied Science, and on the other side is a growing list of increasingly perturbed community-based groups, labor unions and local and international “advocacy” groups. With tensions mounting, the civic society advocacy groups are calling for a temporary suspension of this study to review not only participant safety—including investigators, coordinator and others involved—as well as a review of the perceived lack of transparency and community engagement as is required in South Africa. This study gets more costly by the day.
The Clinical Trial
As the SARS-CoV-2-driven COVID-19 pandemic spreads and takes more lives (over 435,000 as of this writing), health authorities around the world push for a vaccine that can stop the pathogen. Strategies to prevent illness and death of health workers are of particular concern, especially in some countries with significant shortages. Otherwise, continuous patient care becomes at risk with spikes of COVID-19 cases. In developing economies, such health crisis’ can exponentially disrupt societies—from widespread health ailments to economic devastation.
Hence the frantic push for COVID-19 vaccine studies worldwide. TrialSite News has introduced research initiatives centering on Bacillus Calmette-Guerin (BCG), a vaccine against tuberculosis (TB). This vaccine also happens to have protective, non-specific side effects against other respiratory tract infections in vitro and in in vivo studies, with reported illness and death reductions up to 70%. At least ten BCG-based COVID-19 vaccine studies around the world have been launched, including this one in South Africa.
This study commenced in May, led by Cape Town-based CRO TASK. Recruiting up to 500 participants, the study team administers the TB shot to determine if the BCG could aid health workers from developing serious COVID-19.
A number of organizations, from representatives of the trade union known as Cosatu (actually a federation of many unions) to South Africa’s Treatment Action Campaign and the Vaccine Advocacy Research Group (VARG), are advocating for the suspension of the clinical study and re-review of the study by both the South African regulatory authority, known as the South African Health Products Regulatory Authority (SAHPRA), and Pharma-Ethics, the ethics committee that initially cleared the study in the first place.
In a written statement, the group demands a suspension and review, declaring, “We are in full support of all research that is ethical, truly community-owned and accountable to the communities it purports to be in service to.” This statement was also signed a Kenyan chapter of the International Stop TB Partnership network. It just so happens to be that Zweli Mkhize, the South African Health Ministry is a Stop TB partnership board member.
The Group has intensified its public relations campaign for action claiming two fundamental issues that need resolution, including 1) the clinical trial sponsor hasn’t’ met its community consultation and engagement responsibilities, and 2) the trial is putting health workers at risk for not providing PPE as part of the “standard of care.”
These issues are reviewed for the TrialSite Network. That a clinical trial isn’t meeting its legal, regulatory or ethical standards is a serious matter that merits better understanding. Inherent in this conflict is a lack of thorough planning by the sponsor that has opened the door for the costly potential of delay and politicization.
Lack of Community Engagement?
The first issue centers on the duty of a pharmaceutical sponsor to provide community engagement around a clinical trial. International standards, from the International Conference for Harmonization of Technical Requirements for Pharmaceutics for Human Use or (IHC), to the World Medical Association’s Helsinki Declaration establish the imperative of the “standard of care” but do not address a communities involvement in a clinical trial.
As reported in Cape Town’s News24, the most recent 2006 recommendations from nation’s Department of Health involving Good Clinical Practice Guidelines suggest sponsors (and CROs) consider the establishment of a community advisory board in support community engagement and transparency for local South African studies. Consisting of community members where the clinical trial is conducted, the boards could consist of religious or tribal leaders where tribal members are subjects of a study as an example.
Introducing the concept of “community involvement,” the guidelines suggest “research to be carried out at a community level (e.g. vaccine trials) should ideally ensure adequate consultation with civil organizations that may exist within affected communities at all phases of the trial.” Hence, the concept of Community Advisory Boards are introduced as recommended in the nation with the continent’s second largest economy as measured by GDP.
Hence in South Africa today, most major HIV and TB clinical trials include such bodies to ensure healthy communications between sponsor and communities via standard community meetings as highlighted in the document titled “Good Participatory Practice Guidelines for TB Drug Trials 2012.”
Sponsor TASK retained a group called TB Proof to ensure local community participation. They reported to the news outlet Bhekisisa that information about the clinical trial was distributed to a number of WhatsApp groups and social media platforms, reaching what they estimate was approximately 2,000 healthcare workers. Moreover, the group conducted a May 27 meeting involving diverse interests centering on the clinical trial. TASK investigator Caryn Upton noted TB Proof’s mission was to advocate for protection of health workers and that they were consulting on the trial and fulfilling the community engagement purpose.
The opposition (e.g. community groups, union members, etc.) argue that TB Proof serves as a sort of a token not offering any meaningful updates nor are they responsive to key concerns around health and safety of study workers or subjects. They point to an admission that TASK directed TB Proof to not engage with community members and activists at a June 11 civil society meeting as explicit evidence to their point. The crux of the matter was summarized by TB Proof stating, “There appears to be disagreement among organizations regarding what constitutes ‘engagement.’”
Lack of PPE
The TASK study is not providing any study workers with PPE nor was protective equipment considered as “standard of care” for subjects. Interestingly, in this case, the costs associated with such a responsibility falls on the public sector via the Western Cape health department. As it turns out, this public health agency, and others across South Africa, have experienced PPE shortages since the advent of the COVID-19 pandemic. These shortages have directly impacted study teams, such as those in the TASK BCG clinical trial. There just isn’t enough PPE to go around.
Ms. Upton, the TASK investigator, informed Bhekisisa that the study didn’t have the funds to offer PPE to participants and moreover that it wasn’t a standard practice for international trials to ensure volunteers had access to such important gear. Consequently, TASK has approached the South African Medical Research Council to help with the funding for PPE.
A critical question surfaces from all of this: what are acceptable standards for a clinical study team in the middle of a pandemic? Moreover, for participating subjects should the standard of care be extended to PPE. A question to consider: What are the implications if it turns out that in the developed world it is assumed that a patient coming to a hospital or health clinic for a study could expect to have access to PPE but in developing economy nation this expectation isn’t available? Is the “standard of care” a global edict of a local reality?
In the context of a global pandemic, a clinical trial seeks to investigate whether a BCG vaccine can stop COVID-19: an important and urgent question. The study is operating in South Africa where the concept of community engagement (and associated transparency) were put in place due to a number of factors and historical considerations associated with clinical research on the African continent.
That study team members aren’t given adequate PPE is certainly a concern as the COVID-19 pandemic rages on. TASK was savvy enough in its negotiations to externalize the cost of PPE to the local health authorities. But unfortunately, the savvy move to save money upfront could backfire and hurt the study. After all, given the state of affairs with COVID-19 today, wouldn’t it be considered reasonable to ensure the protection of the very study team that the experimental vaccine trial has been established to hopefully protect?
Hence, the groups calling for a temporary suspension and regulatory and ethical committee review have a point if study team members and participating subjects don’t have access to PPE. Is the study worth having if everyone involves gets infected with COVID-19?
Given the growing attention, focus, and tension, TASK is naturally moving into a defensive mode with growing calls by organizations such as the Treatment Action Campaign for not only an ethical and accountable trial, but one that is “community-owned” and “shared by a comprehensive consultative process that is led by the community that the trial purports to serve: healthcare workers.”
Undoubtedly, South Africa promulgated community engagement recommendations and guidelines for good reason based on various ethical shortcomings of past studies. However, there certainly is a difference between a well-run, properly governed, safe, ethical and collaborative study that supports community transparency versus one that is hijacked by myriad interests for whatever local agenda or purpose—one that wants to “own” the study. This turns into something very different.
Unfortunately, one shortcut to save money can literally become a portal into an expensive and disorderly, not to mention complicated, entanglement that could have been completely avoided by good holistic planning up front. Because PPE was externalized to a group that didn’t have any, the cost of this trial, not to mention the duration, is about to become greater while COVID-19 continues.