The Deeper Data Debate

Since the mid-1980s, Belgium has been a very active clinical research territory in Europe. Currently, it is far more active than its neighbors or the United States in terms of new clinical trials per million inhabitants per year.

This is due to the qualification of Belgian investigators and their staff; the concentration of technology at the sites; the high level of education of the population, allowing participants to comprehend the purpose of complicated trials and thus to provide informed consent; and the high standard of living, which enables patients to defend themselves in case of investigator abuse (e.g., the means to access a lawyer and a functioning legal system).

Jean-Pierre Tassignon, MD, PhD

Through the globalization of research, sponsors and CROs have discovered by trial and error sites with an enrollment productivity three to 10 times greater than in economically advanced countries like Belgium. Twenty years into the globalization process, are we sure it is acceptable to pool data from extremely diverse origins, including from countries where:

• The investigator is in a dominant position vis-à-vis the patient, such that patients minimize adverse reactions and maximize the effect of the investigational product to "please the doctor?"

• A vast proportion of the population lives in poverty, for example, with a GDP per capita below that in the EU Member State with the lowest GDP?

• Access to health care conforming to disease-specific guidelines in advanced countries it is not available routinely, or where our level of standard of care is so unaffordable that the financial and logistic intervention of the sponsor is required to ensure that local participants receive it in the context of the trial?

A contrario, it is perfectly adequate to accept clinical data exclusively from poor countries where the primary disease studied in the trial is much more prevalent in the poor countries of the world.

The mere equivalence between countries of baseline characteristics of participants in a study concerning sex, biometrics, risk factors, and disease markers is not enough to justify the indiscriminate pooling of clinical results from all over the world. The transnational pooling of clinical data should be justified by demonstrating equivalence in relevant health care and socio-economic standards in the countries participating in the trial.

Equivalence should be demonstrated in the qualifications of health care staff involved in the research, in the capacity of participants to give free and informed consent, in the availability of alternative care if the participant turns down the trial, as well as equivalence in local standards of care. The latter is closely related to GDP per capita. Infant mortality rates and life expectancies for males and females correlate with living standards and the quality of health care in the population, and therefore differ enormously between countries. How different can the health care environments be from where trial data is derived to still justify transnational pooling?

The probability of a GCP inspection of participating sites is much higher in the EU and North America than in the rest of the world. Trials migrate today to regions of the world where the probability of a GCP inspection, and thus the detection of fraud and misconduct and corresponding sanctions, are close to nil.

Our standard of care in the future in Europe depends on clinical research with new products today. However, testing these new products in vastly inferior health care and socio-economic environments favoring hyper-fast recruitment solves only the sample size challenge.

Jean-Pierre Tassignon, MD, PhD President and CEO Crossover CRI AG jean-pierre.tassignon@crossover-cri.com www.crossover-cri.com