The United States Agency for International Development (USAID) was established by President John F. Kennedy in 1961 and is responsible for overseeing foreign aid and development assistance. The current Executive administration has launched an assault on the Agency, beginning with an expansive freeze on foreign aid, followed by specific attacks on the USAID itself. Most of the activities have been halted. The majority of employees are slated for layoff or suspension.
If you familiarize yourself with the activities of USAID, the chaos and cruelty of its abrupt deconstruction are self-evident and already demonstrable. Workers who have dedicated their careers to serving needy communities are suddenly adrift in a foreign land, cut off from communication with their peers, and forbidden from even the most humane gestures toward the communities in which they have worked and collaborated. The communities who have benefitted from the USAID are suddenly cut off from lifesaving food, medicine, and other resources without the time to explore and implement alternative arrangements.
There is one particular casualty of the assault on USAID which hits close to home for me. As reported by several media outlets including Science, the New York Times, and others; more than 30 clinical trials have been interrupted and likely terminated. The interruption or termination of these trials is tragic on many levels. It epitomizes the indiscriminate, cruel and wasteful nature of these abrupt measures.
A word on clinical trials
A clinical trial is a research study in which people (study participants) are assigned to some intervention(s) or strategy. Study participants are followed in a prospective manner to assess the effects of those interventions. Often, this involves the direct comparison of 2 or more strategies, which may include control groups (including placebos). As someone who has been involved in many aspects of clinical trials,I will try to communicate consequences of these sudden disruptions on a more personal basis.
There are aspects to clinical trials that outsiders may not fully appreciate. Clinical trial participants are the unsung heroes of progress in biomedical research. They are volunteers. In order to qualify, they undergo a screening process and detailed informed consent. Study participants must accept that there are risks, with no certainty of benefit. They typically commit to time, testing, and inconvenience far in excess of conventional care. One of the key motivations expressed by clinical trial participants is the hope that knowledge gained through their participation will benefit others.
Clinical trials may go on for months or years, and often involve dozens of interactions with study participants. Research coordinators and other team-members often spend hours with clinical trial participants and their families. Speaking from personal experience, there is a special relationship that develops between investigators, research staff, and participants in clinical trials. Responsible investigators recognize the sacrifices and risks that their study participants accept. I made a conscious effort to be especially generous of my time and attention to clinical trial participants. Research coordinators and support staff are ambassadors, communicators, schedulers, etc. Those with whom I have worked have been incredibly dedicated professionals. They are the lubrication and the glue that make clinical trials run effectively. The bond and trust that participants form with clinical trial staff is the “secret sauce” of successful clinical trials.
Reportedly, over 30 clinical trials have been abruptly halted. A complete accounting of the trials is difficult because public records have been hidden. Here is a sample of the interrupted study interventions:
- A device to prevent HIV transmission and pregnancy
- HIV vaccines
- Long-acting HIV prevention
- Malaria treatment in young children
- A malaria vaccine
- Treatment for cholera
- A screen and treat method for cervical cancer
- Multiple tuberculosis treatments
Indiscriminate
These trials were not launched recklessly or indiscriminately. They were approved by appropriate ethical review committees. They were awarded based on merit and priority. They were implemented because they were expected to answer important questions. In contrast, the suspension/termination of these studies was done indiscriminately, apparently without consideration merit or potential benefit, and also without regard for the consequences of termination. None were spared.
Cruel
The indiscriminate termination of these studies was a cruelty imposed on the study participants and to the investigators, but perhaps the greatest cruelty is to the world at large, because potentially life-saving and health restoring treatments will be delayed or permanently foreclosed.
The participants in each of these studies made a commitment to accept the terms of the study. The sponsors and investigators also made a commitment supervise the trials ethically, including the commitment to protect the participants from unnecessary risk. Arbitrary termination of these trials is a betrayal of an ethical commitment to the participants who volunteered.
Once enrolled, investigators are obligated to monitor participants for potential harms from their participation, to mediate those harms to the best of their ability. The stop-work orders prohibited the investigators from fulfilling that commitment, leaving study participants vulnerable. In one clinical trial, young women received implanted devices to prevent HIV transmission and pregnancy. On termination of the study, it would be dangerous, cruel, and unethical to leave the experimental devices in women who could no longer be monitored; yet the stop-work order prohibited further contact. Complying with the order would require abandoning the study participants. Investigators were given an excruciating choice of honoring their ethical commitment to their study participants or obeying the stop work order. This is cruelty to the women as well as to the investigators.
Volunteers surely hope that they will benefit from their involvement, but they enter clinical trials with the understanding that there are risks with no assurance of benefit. They are often motivated by an altruistic hope that knowledge gained through their participation will help others who are similarly afflicted. I have heard this over and over in my interaction with study participants. If a study is terminated without scientific justification, the study objective usually cannot be achieved. The primary question will not be answered. For the participant, this will decrease the potential for personal benefit, may increase the personal risk, and destroy the hope of vicarious benefit to others and to society. These participants have endured the risk and much of the benefit has been stolen. It is a betrayal to the volunteers on every level.
Wasteful
Running a clinical trial is a little like building a bridge. A great deal of planning takes place before construction of a bridge. Similarly extensive planning takes place before beginning a clinical trial.
The conduct of the clinical trial is like the construction stage of building the bridge. If construction stops prior to reaching the other bank, the bridge is useless. It doesn’t matter how noble the intent, how elegant the design, how flawless the construction, or how great the cost; the project has not achieved its goal of providing a conduit from one side of the river to the other. If a clinical trial is terminated prior to the prescribed end, the question the trial was meant to answer will remain unanswered and much, if not all, of the resources invested will have been wasted.
Here is where the analogy breaks down. Construction of a bridge may resume and be completed at some time in the future without diminishing the designers’ intent. Not so for a clinical trial. Clinical trials are run according to strict protocols. Compliance with a protocol is never perfect, but total abandonment of the protocol, even for a limited time creates major problems. Once the study is stopped, it may not be possible to resume. Some participants may be unreachable, some may decline to participate due to broken trust with the investigators. Some may have taken medications otherwise engaged in activities that would invalidate their results. Some may have died. Even if all the participants could be assembled, interruption of the experimental treatment would likely make the study outcomes uninterpretable.
There can be justification for interrupting a study early. A study may be paused if the interim results are definitive, if the risks of continuing the study are too great, or if it becomes clear that the study has little to no potential to reach a meaningful conclusion. Often contingencies for these pauses are prespecified in the study protocol and based on the advice of an independent review committee which has access to the data. In each of these examples, certain aspects of the study may be stopped or modified BUT, the study participants are not abandoned. They will often be debriefed on the reasons for modification of the protocol. They will continued to be monitored for safety, and treated as appropriate.
For the USAID supported clinical trials, I am aware of no scientific or ethical justification for their termination. There is an excellent chance that the results of these studies would have produced impactful results. That possibility has been foreclosed. All resources that have already been used for these studies have been wasted.
These trials were funded because they had potential to generate data that could improve health and reduce suffering. Running a trial on treatment of tuberculosis in a country with a high rate of tuberculosis has certain efficiencies and results of the study have the potential to improve the health in that country. But the benefits do not stop there. The results may be quite impactful elsewhere. Tuberculosis is prevalent across much of the world. Cases are increasing in the United States. The largest outbreak of tuberculosis on record was reported in Kansas City this year.
Trials in the USAID portfolio could have led to the prevention and/or more successful treatment of diseases like tuberculosis, malaria, HIV, cervical cancer, and cholera worldwide. Now they will not. This is the greatest cruelty and waste of all.