Biomedical Engineering Reference
In-Depth Information
16.3.5 Efficacy, safety and risk
Clinical research can be justified only when the potential risks to the trial
participant are minimised, the potential benefits to individual subjects are
enhanced and the potential benefits to individual subjects and society are
proportionate to or outweigh the risks (emanuel
et al
., 2000). a suspicion
of equipoise with regard to a specific trial has to exist in order to justify it.
it must be unclear at the start which of two treatments is the best for the
patient under the given circumstances: applying the BTeP or an established
intervention (Freedman, 1987).
Successful regeneration will be greatly beneficial for the patient, returning
him or her to greater functionality and postponing the need for further
interventions or even making them redundant. if however the attempted
regeneration fails, especially when other therapies are available - even when
they are theoretically 'second best' to tissue engineering - the intervention
may turn into a hazard. one of the challenges in bone tissue engineering
clinical trials is therefore the identification, weighing and minimisation of
risks. These risks are partly unknown owing to our lack of understanding
of the long-term evolution of the BTeP in the body and of the induced
regeneration of human tissue
in vivo
. a number of potential hazards and
approaches to minimise them can nevertheless be identified (Farrugia, 2006;
Halme and Kessler, 2006). First, criteria for cell choice and cell quality
need to be established. This does not only concern the choice of the cell
type (es, msc, fully differentiated cells), but also the choice of cell donor
or cell line. second, there is the potential alteration in the genetic make-up
during cell culture and expansion and the presence of unwanted cell types
or contaminants in the administered BTeP. standard treatments to enhance
safety, such as sterilisation or irradiation, may not be applicable. establishing
good tissue practices and good manufacturing practices will consequently
be crucial for the successful development of BTePs (emea, 2002; emea,
2003).
Third, the evolution of the BTeP in the body must be monitored and
controlled in order to detect and prevent undesired cell migration, propagation
or (de)differentiation and not to evoke rejection or inflammatory responses
by the host's body. all these new risk factors come on top of more 'common'
risks associated with cell culturing and surgery. There has been so far little
attention to the assessment of these 'common' risks in trials with BTePs,
or to the influence of boundary conditions on the action of BTEPs (Kuijer
et al
., 2007; Lumelsky, 2007).
While many of the risks cited here are also present in other medical
technologies, it is the complexity of tissue engineering that leads to an
inflation of uncertainties, perhaps even provoking new emergent risks caused
by hitherto unencountered interactions of various processes going on in the
