(2002; 166 pages)
Cross-border movement of clinical trial subjects
Dr Alar Irs, Estonia
In 1998-99, a cross-border clinical trial took place involving 135 healthy volunteers recruited and screened in Estonia. The subjects were transported to Switzerland for the early phase of the trial which was carried out by a contract research organization (CRO) and sponsored by several major pharmaceutical companies. The Swiss drug regulatory authorities and an independent ethics committee (IEC) in Switzerland were notified of the studies.
The Estonian State Agency of Medicines (SAM) learned about the study and an inspection was carried out at the premises of the recruitment in Estonia. As a result, the SAM concluded that since the study had begun in Estonia, it should have been approved by an Estonian ethics committee and by SAM. Inspection also revealed that the subjects had not been provided with sufficient patient information, neither in Estonia nor in Switzerland. Consent forms were in English or German, languages that many of the subjects did not understand and monetary compensation had been paid to the subjects for the 1-2 week study equivalent to several months’ salary in Estonia. In one case, it emerged that a recruitment doctor had recommended to a patient not to inform the investigators at the CRO of concomitant therapy, although this could undermine the validity of the data. No medical follow-up was provided to the trial subjects.
All activities in Estonia related to the trial were stopped by the inspection and a report was forwarded to the Swiss regulatory authority which conducted further investigations in Switzerland.
The Estonian Medicinal Products Act was subsequently amended by parliament, because it was found that the point of commencement of a clinical trial was not specified in legislation. The Act now states that “Dissemination of information concerning a clinical trial to possible trial subjects or performing of procedures related to the trial is deemed to be the commencement of the clinical trial”, thus requiring ethical and SAM approval before the recruitment of subjects can start. This is in line with good clinical practices (GCP).
The following conclusions can be drawn from the above case:
• It remains open whether the benefits of such research justify the risks involved.
• Review of a trial by an ethical committee in a different country to that where recruitment takes place does not comply with international guidelines. Also, such a procedure cannot adequately evaluate the influence of travel and monetary compensation (even if appropriately addressed in the application) on subjects from vulnerable or low income groups.
• It is also difficult to address informed consent procedures and medical follow-up in such “mobile studies”.
• Cooperation between drug regulatory authorities is absolutely vital to ensure the protection of clinical trial subjects and the integrity of data in international pharmaceutical research.