Background and development of the study

The “Study Group on Analgesics and Nephropathy (SAN)” was prepared for late in 1998 and finally set up with the foundation of the “Scientific Board” (SB) in March 1999.

The initial question as to whether the available evidence of the postulated relationship between the development of nephropathy and the use of phenacetin-free (combined) analgesics was sufficient for recommending regulatory consequences was negated by this scientific committee in a consensus paper and was published (Kidney International Dec. 2000).

The conclusion that any relationship can neither be proved nor rejected due to a lack of suitable data gave rise to the demand for an epidemiological study approaching this question.
After another expert meeting discussed the role of caffeine in combined analgesics and the resulting conclusions were also published in an acknowledged international journal (Clin. Pharm. Therapeutics 2000), the design of an epidemiological study has been developed starting in September 1999.

After a first test of the concept, its defence in the SB meeting (May 2000), countless input was given in agreement with the Drug Authorities of the three countries involved, which led to numerous protocol amendments.
The detailed documentation of the course concerning timeframes and contents up to the beginning of the case-control study is available on request.

After consent to the study protocol by the last one of the involved Drug Authorities in March 2001, the study was officially placed with the German Kidney Foundation and the Austrian Society for Nephrology.

Since the beginning of the case-control study on nephropathy and use of analgesics (official study title for methodological reasons: “Health and Lifetime Exposure to Chemical Substances”) the following activities have been performed by the research association:


1. The study protocol, which was subject to numerous minor changes since the completion of the pilot phase and approval by the SB of the SAN study group due to requests by the Drug Authorities, was officially submitted to the German Kidney Foundation for review and approval as a research project in March/April 2001.

2. After approval by the external experts appointed by the German Kidney Foundation the protocol and thus the research project was released for implementation. Deliberations among the Boards of the Nephrological Societies of Germany resulted in positive and supporting opinions (April/May 2001). The Austrian Society for Nephrology gave their general approval to the project in June 2001 and measures for implementation were initiated.

3. In March – April 2001, ZEG Berlin set up the final versions of the study material: Questionnaire I (interview) and II (medical record form), including layout, instructions for interviewers and for completion after changes had been made, code lists and lists & tables (picture atlas for drugs) for the interview and study information sheets for cases and controls. For Austria, the mentioned material – in particular the medication lists – were compiled early in July and forwarded for conducting the interviews

4. The authorised commissioner for data protection and file access from Berlin approved of the study on May 21, 2001 and had no objections concerning Patient and Subject Informed Consent Forms, the information letters for patients and controls and the declaration on data protection as well as the record forms.

Approval of the study by the Ethics Committee of Ärztekammer Berlin was obtained on June 01, 2001. No fundamental ethical concerns against the beginning of the study were expressed.

The Ethics Committee of the Medical Faculty of the University of Vienna and of the General Hospital of the City of Vienna have also approved of the study on July 09, 2001.

5. For the qualified and standardised conduct of interviews, three interviewer training sessions were held by ZEG in Germany: the first one took place on May 17, 2001 in Nuremberg, the second one on May 18, 2001 in Berlin, and the third one on November 23, 2001 in Nuremberg again. The interviewers were recruited in co-operation with I+G Nuremberg who are also involved in the co-ordination and monitoring of the work of the interviewers. In Austria, a team of interviewers was set up. Their training session was held on July 19, 2001.

6. The first 500 control interviews (to check the assumptions made for sample size calculations in the protocol) were held in July.

7. The Data Base of Analgesics for Germany and Austria have been set up and are being complemented continuously.

Since unexpectedly access to an existing data base of analgesics of the “old Bundesländer” was not possible and further waiting (with insecure result) was not possible either because of the preparation of the analyses for the SAC meeting, the set-up of a new data base was agreed upon in a meeting of the study investigators (Managing Committee) in mid-June. For this purpose, the drug registers of both countries and the AMIS data base were used as sources, and manufacturers both in Germany and Austria were directly contacted in order to validate existing data.

The data base of analgesics in the “new Bundesländer” (Data Base East) was finalised in September 2001. The newly established data base of the “old Bundesländer” (Data Base West) has also been nearly completed. Both data bases are available in Excel format and can be used in this format in the future. Both data bases will be joined into one data base of German analgesics as soon as final additions to the Data Base West have been made. It will be decided upon in the course of the study, what improvements concerning easy and convenient use seem to be useful. It is planned to make a user-friendly data base of German analgesics available later (Public Use File).