Case-control study on analgesics and nephropathy (SAN): protocol

Abstract

BackgroundThe association between intake of non-phenacetin-containing analgesics and the occurrence of chronic renal failure is still controversially discussed. A new epidemiologic study was planned and conducted in Germany and Austria.Methods/designThe objective of the international, multicenter case-control study was to evaluate the association between end-stage renal disease (ESRD) and use of non-phenacetin-containing analgesics with particular emphasis on combined formulations. A targeted sample of 1000 new (incident) dialysis patients, aged less than 50 years, was planned to recruit between January 1, 2001 and December 31, 2004. The age limit was chosen to avoid contamination of the study population with phenacetin-containing analgesics to the extent possible. Four control subjects per ESRD case, matched by age, sex, and region were selected from the population living in the region the case came from.Lifetime exposure to analgesics and potential renal risk factors were recorded in a single face-to-face interview. A set of aids was introduced to reinforce the memory of study participants.A standardized, pre-tested interview questionnaire (participants), a medical documentation sheet (physicians in dialysis centres), a logbook for all activities (dialysis centres) were used to collect the necessary data.Quality management consisted of the standardized procedures, (re-) training and supervision of interviewers, regular checks of all incoming data for completeness and plausibility.The study is scientifically independent and governed by a international Scientific Advisory Committee that bridged the gap between the sponsoring companies and the investigators. Also other advisory groups assisted the managing committee of the study. All relevant German and Austrian nephrological associations supported the study, and the study design was carefully reviewed and approved by the Kidney Foundation of Germany.DiscussionThe study is expected to answer the main research question by end 2005. There is however a high potential for various biases that we tried to address with adequate measure. One limitation however cannot be overcome: The methodologically needed age-limitation of the study will make it not easy to generalize the results to age groups over 50 years. It might be suggested to repeat the study for persons over 50 years in 10 years when contamination with phenacetin use early in life is likely to be outgrown.

Analgesics use and ESRD in younger age: a case-control study

“…The study protocol was reviewed and agreed to by the Scientific Advisory Committee, was accepted by the regulatory authorities of Germany, Austria, and Switzerland, and was reviewed and approved by the Kidney Foundation of Germany. It was supported by the three Nephrological Societies in Germany and the Nephrological Association of Austria, published in BMC Nephrology [ 11 ], shown on an open-access website [ 12 ], registered as clinical study in the FDA website (Protocol Registration Receipt NCT00302835) [ 13 ], and approved as a study protocol by the Lancet.…”

“…This strategy was adopted to account for the potential differential recall of trivial use in cases and controls, based on the notion that controls may have poorer recall of irregular and low use than cases despite all standard memory aids used (cf. protocol published in this journal [ 11 ]). The decision was approved by the SAC after discussion of intermediate analyses and became integral part of the analysis plan.…”

“…Several index dates were defined and examined to determine the most appropriate lag time between exposure to analgesics and the start of dialysis. The decision was made that exposures in the 5 years prior to start of dialysis should not be used in analyses concerning ESRD risk [ 11 ] because analgesic use may have been initiated due to incipient kidney disease during that time.…”

“…Crude and adjusted odds ratios with 95% confidence interval were calculated. The decision was made a priori to use unmatched analysis if the risk estimates of matched analysis did not materially differ [ 11 ]. This is because less information is lost in unmatched analyses and these are therefore better suited for subgroup analyses.…”

“…The board was aware that the analysis would address several subgroups, including analgesics co-formulated with caffeine. The design efforts resulted in a detailed, published study protocol, confirmed and approved by the regulatory authorities [ 11 ].…”