Community involvement in clinical trials: From the U.S. to Western Europe

In many countries, HIV-positive activists today not only participate in the management of service organizations and sit on their boards and governing committees, but are also involved in shaping research policy and its implementation. Of course this has required constant effort to convince officials and politicians of the importance of having the input of affected communities. The first and great victory for community involvement in clinical trials was the establishment in 1990 in the United States of Community Advisory Boards, which oversee clinical trials funded through the AIDS Clinical Trials Group (ACTG), a U.S. government funded body created in 1987 to shape the AIDS research agenda and set standards for HIV drug trials. Building on the Denver Principles and the power of AIDS activist groups such as ACT UP NY, within one tumultuous year from late 1989 to late 1990, HIV activists first showed up, uninvited, to an ACTG meeting; then came, invited as observers; and finally pushed their way onto ACTG governing bodies. [2]

Activists to the forefront
Shortly after those events unfolded in the United States, a group of European AIDS activists and doctors created their own initiative, the European AIDS Treatment Group (EATG), [3] whose goal was to push for a universal standard of care and widespread access to new medications. The EATG was, and still is, heavily engaged in sharing treatment information and training people about scientific research and lobbying, thus strengthening long time treatment activists and creating new ones. At first some may feel intimidated by all this technical jargon but practice has proved that even people with no medical background can learn it with a little hard work. The EATG provides a forum to the HIV community to discuss and form policies and act as an equal stakeholder along with the government, regulatory authorities, physicians, and pharmaceutical companies. With the latter it negotiates issues such as compassionate access to experimental medications for people who have no other treatment options, and regularly discusses such issues as clinical trials, side effects, quality of life, and new formulations.

During our interactions with companies and researchers the EATG encountered a number of difficulties in ensuring timely and consistent input with regard to clinical trials. Community involvement was erratic and was far too dependent on the initiative of drug companies who invited EATG representatives when and where they chose. Furthermore, we needed advanced training to be able to express ourselves with the necessary terminology, if we wanted to be heard and be taken seriously.

The ECAB is born
In late 1997, the EATG came up with a solution: we set new rules on how community advice was to be sought and created a new vehicle to channel that advice: the European Community Advisory Board (ECAB). The ECAB now meets on regular, pre-set dates, where we can invite companies and researchers to meet with us. We use a hotel and meeting room of our choice and they come as our guests and the meetings happen on our terms. We use those opportunities to share information amongst ourselves and conduct trainings to increase our knowledge on topics like: e.g. research methodology, statistics, pharmacology, immunology, virology, resistance, regulatory processes, vaccines, diagnostics and more.

In the end though, ECAB’s central task is to examine trial protocols and give input to the trial design, with special attention to inclusion and exclusion criteria, and to ensure that patient information leaflets are comprehensible to prospective trial participants and thus ensure true informed consent. We serve as watchdogs who pressure companies and doctors to design trials that reflect the real world and, above all, safeguard the safety of the participants.

Companies prefer to exclude patients with liver abnormalities (e.g. people co infected with Hepatitis C) so that their drugs perform as well as possible. They like to exclude people who have a history of ”abusing drugs“ (a typical term), because companies consider them to be unreliable. Because of the political climate created by the so-called war on drugs in the United States, where the majority of trials are designed, the companies have no interest in studying interactions between their medications and illicit drugs. Even getting companies to study methadone interactions took some convincing until regulatory agencies began to require it. Since its founding, ECAB has been battling away against all of these forms of discrimination that are based on prejudice and politics, and not science.

The ECAB and beyond
Today ECAB consists of 50 members from around 30 countries and meets regularly in Brussels. We have achieved recognition of our work from the European Medicines Agency [4] (the body that regulates drug licensing) and companies are expected to seek our input and approval regarding drug development and early access to new medications. But not all is rosy. Some time all we hear back for our comments is: ”point well taken“. Recently ECAB met with a company to discuss a trial design. The second of the exclusion criteria read: ” [Patients with] Current or past alcohol and/or drug use which in the investigators opinion, could compromise the subject’s safety or adherence to the study protocol“. This highly inappropriate wording not only reflects existing prejudices; it perpetuates them and makes value judgments based on lifestyle choices. Instead we suggested a warning or guidance could perhaps be given to the doctors for patients that have demonstrated e.g. failure to keep appointments as an indicator of potential poor adherence. And while there is no evidence that alcohol or drug use results in one, numerous studies have demonstrated beyond doubt the inability of the doctors to predict the adherence success rates of theirs patients. Unfortunate as such prejudices are for the Western countries, imagine the possible consequences in the setting of countries with limited access to these life- saving medications. It would be the same doctors that would later have to make the choice of who ”deserves“ to be treated or who is not likely to ”harm oneself“ by ”improper“ use of the medications, posing also a threat to others due to the emergence of resistance.

On other occasions we feel we have achieved our goals like when last year, for example, we raised our concerns for a trial conducted by Schering-Plough which, after some tough negotiations, led to the change of the original protocol just before the trial was about to begin. This was the first time such a thing had ever happened in Europe. Our point was to raise the level of safeguards to potential trial participants at the expense of quick recruitment.

This last point has made ECAB increasingly concerned by the preference of drug companies to set up trials in Central and Eastern Europe and even to developing countries because of the difficulty of finding enough available treatment-naïve patients to participate in trials in the Western countries. In Central and Eastern Europe, by contrast, people with HIV have such difficulty accessing treatment that they are more than eager to enroll in an experimental drug trial. Well designed trials are of course most welcome but should only be offered along side affordable and unhindered access to the standard of care for all patient groups. The HIV community in these regions should be alert to the potential for abuses and exert all possible pressure to be informed and involved.

To that end the EATG will organize a seminar for AIDS activists in Eastern countries later this year with the aim to empower and train local activist to get involved and give their input and come up with their set of priorities and demands. They would also be more than welcome to join ECAB and use it to find out how they can influence things from that front as well.

Nikos Dedes, Chair of the European Community Advisory Board

References

1. Denver Principles, 1983 see more: http://www.actupny.org/documents/Denver.html
2. See more at: http://aactg.s-3.com/pub/docs/CCG-CAB-history.htm
3. See EATG’s web site at: www.eatg.org
4. http://www.emea.eu.int

EATN - European AIDS Treatment News, Volume 13, I – Spring 2005

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