Well, I think that in liver transplantation there is no prospective, independent and randomised mutlicenter study which is large enough and has enough power to show that cyclosporin or any form of tarcrolimus has superior results for the patients - used as induction therapy or long term. If somebody thinks there is, I would like to see one.

Thank you Krist for this comment. I will respond with some citations:

"...Observational data bases can be useful adjuncts to randomized, controlled trials, to see whether efficacy under controlled conditions in specialist centers translates into effective treatment in routine practice..." Stuart et al. NEJM 2000.

“..The popular belief that only randomized, controlled trials produce trustworthy results and that all observational studies are misleading does a disservice to patient care, clinical investigation, and the education of health care professionals...The results of well-designed observational studies do not systematically overestimate the magnitude of the effects of treatment as compared with those in randomized, controlled trials on the same topic..." Concato et al. NEJM 2000.

"...Registry-based studies offer a number of advantages over clinical trials or prospective cohort studies. They are relatively quick and inexpensive to conduct, and ethical approval is often straightforward. Typically, registries allow for many more subjects than would be feasible with primary data collection; the larger sample size and multicenter nature of many registries enhance study power and allow researchers to conduct sophisticated multivariate or multilevel analyses. Registries also draw from more transplant centers than would be feasible in most cohort studies (in particular at small or nonacademic centers)..." Massie et al. AJT 2014.

"...Theodore Roosevelt once said, “Do what you can, with what you have, where you are.” Today we can no longer afford to undertake randomized effectiveness trials that cost tens or hundreds of millions of dollars. But today we also have registries and other powerful digital platforms. Today it may be possible to design and conduct megatrials with what we have: bigger data and smaller budgets. Yet we must also recognize and acknowledge the daunting challenges that diverse groups of researchers and stakeholders must overcome to get there." Lauer et al. NEJM 2013.

We are in the era of the so called BIG DATA & Analytics that explore even non-structured data thanks to the increasing power of computers. Successful businesses swear by this. I think that we can believe that clinical registry data, which is structured, audited and controlled can contribute to the choice of imm. treatment in the future.

We have been using Advagraf as induction immunosuppression since its delivery in Europe in 2007, more than 400 hundred patients so far. Beyond the recent study from the Europen Registry all the published studies have been focused to demonstrate non-inferiority of Adv vs Prograf with follow-ups no longer than 1 year in most of the cases. The study from the ERLT demonstrating better survival with Adv must be seen with caution because the authors show 3-year patient survival but only 50% of the patients were followed up to 12 months, less than 30% up to 2 years and only 15% up to 3 years. Moreover, this study has the pros and cons of a registry including heterogenicity of policies in the different centers. Anyway, our immunosuppression policy is based on Adv and we have achieved more than 80% 4-year patient survival in a recent study of the first 150 recipients that will be presented at the ATC 2015. Nevertheless, the role of Adv in this good results should be studied.

Thank you Mikel for sharing your experience in Bilbao. It is unfortunate that the Spanish centers do not report immunosuppression data to the RETH so that they are integrated into the ELTR. But I plan to soon offer an alternative to the Spanish centers. Regarding the heterogeneity of rules in centers and in countries of Europe, we recognized the limitations of a registry data analyzes in our paper. However, despite these limitations and using the available variables and propensity methodology, the results showed a superiority of ADV beyond 1 year FU. Of course further studies are needed to explain these results.

Finally, I will be interested to read your abstract to the ATC.

I believe that trustworthy data can be extracted both from RCTs AND observational studies. With respect to CNIs I support Kristers view. But in addition to hard endpoints concerning Advagraf such as graft- and patient survival, there is an additional element that is important for both patients and hospitals. That is the easy administration once daily. Possibly this is also an advantage concerning patient compliance. In our center we start the patients on Prograf during the first week when they tend to be metabolically unstable and then switch them to Advagraf after 1-2 weeks.  

Thank you Tim for sharing of your practice in Oslo. I agree with the fact that once daily administration will improve compliance mainly in young patients.