Case Study 1: The VanTx Case (1999)
Despite the flurry of regulatory documents, recent history reminds us of the need for continued vigilance. The following case studies describe cases where the basic principles of human research have not been followed.
Case Study 1: The VanTx Case (1999)
The 1999 VanTx case in Switzerland demonstrated the need to ensure that research ethics committees (RECs) are free from conflicts of interest.
VanTx was a small contract research organisation (CRO) conducting clinical trials for the international pharmaceutical industry. Situated in Basel, VanTx specialised in conducting Phase I and bioequivalence and bioavailability trials in healthy volunteers. Most of the trials conducted by VanTx were approved by a private REC (Freiburger Ethik-Kommission International (FEKI)) based in Germany with a subsidiary office in Switzerland.
In the spring of 1999, an Estonian newspaper revealed that research participants were being brought into Switzerland from Eastern European countries. Potential participants, students for the most part, were being recruited primarily in Estonia and Poland and then sent to Switzerland to participate in clinical trials and receive payment for their participation. The company behind this ‘trafficking of human participants’ was VanTx.
The Swiss Agency for Therapeutic Products (Swissmedic) opened an inquiry into the affair. Many troubling facts about research participants’ protection were revealed, as well as issues surrounding the scientific merit of the trials conducted by VanTx.
First, a remarkable fact was that this CRO conducted a great number of trials in record time (almost 40% of all Phase I trials in Switzerland over a 4 year period). This impressive turnaround time was considered a significant advantage by VanTx’s clients. And, even if audit reports revealed numerous infringements to GCP requirements, many companies continued to use the trial services of VanTx.
Second, the ‘volunteers’ did not receive any information about the trials in their mother tongue. On-site recruiters, simply explained that they would participate in medicines trials and what the travel arrangements to and from living accommodation in Switzerland would be. Once in Switzerland, participants received additional information in German, English and Russian. However, few participants actually understood any of these languages. Sometimes, experienced participants who had participated in several trials translated the information sheets to the new participants. Then, participants signed a document, considered by many to be a contract, in English or German. Questioned about the signed document, many participants considered they were bound by the document and could not withdraw from research nor seek compensation.
It appears that they were not properly informed of their rights, including:
- Right to withdraw from research at any time,
- Right to receive medical treatment and/or compensation for any adverse effects,
- Right to receive medical follow-up once they returned to their home country.
This highlights the importance of acceptable recruitment processes that are an integral part of the consent process. It is particularly important that the recruitment process be evaluated by a competent REC.
Third, this seemingly rare case involved the recruitment of participants in a country other than the one where the trial was to be conducted. The trial is actually being conducted in several countries since the recruitment process is an integral part of a trial. In such cases, the trial should be considered multi-centred and submitted for proper authorisations and ethics review in every country involved. Estonian legislation has since, made this requirement explicit: ‘The publication of information concerning a clinical trial of medicinal products to possible trial participants […] or the performance of procedures related to the trial is deemed to be the commencement of the clinical trial.’ (§ 87.3 Medicinal Products Act, passed 16 December 2004 and entered into force 1 March 2005).
Fourth, VanTx submitted its protocols to a private REC, FEKI. The inquiry revealed that the CEO of the REC was none other than the principal investigator for VanTx. This clearly compromises the REC’s independence. Swiss legislation on the status of RECs has since been modified. RECs are now considered as bodies that fulfil a role for the protection of research participants in the public interest. When the private corporation FEKI claimed the right to pursue its commercial activities, the Supreme Court of Switzerland confirmed that ethics reviews of projects fell within government responsibilities. It could not be considered a commercial service to be provided to researchers or to sponsors. The Court recognised that the State could decide to delegate this responsibility to a private entity but only under strict conditions.
In the aftermath of this affair, Swiss legislation was strengthened and concrete measures were taken to ensure that public RECs had sufficient resources for their level of responsibility. Certain cantons (states) in Switzerland also created research participant registries that would identify a person’s origins. This helped to avoid research participants becoming ‘professionals’ of trials, e.g. by taking part too often.