Quality Management

Researchers, funding agencies, and the public have recently begun to realize that a significant proportion of the resources spent on biomedical research are wasted. A plethora of treatment strategies for numerous diseases is being developed in laboratories worldwide, including those of the Department of Experimental Neurology. However, despite often being highly beneficial in preclinical models of disease, only very few of these treatments eventually prove effective in patients. At the same time a growing number of studies report on the non-reproducibility of results published in the biomedical literature. Measures to increase quality and value and to reduce inefficiency in biomedical research are overdue: Scientists need to improve the design, conduct, analysis and reporting of their research.

To do so in a structured manner we have established a systematic quality management (QM) system. The aim of this QM system is to implement auditable standards for the planning, realization, evaluation and publication of our experimental studies, and to safeguard compliance to guidelines (such as ARRIVE) and regulations of good scientific practice (GSP). As academic biomedical research worldwide has up to now operated based on trust alone, and entertained the notion that any type of regulation only stifels the creativity of researchers, no precedents for systematic quality management in academic research exists. The emergence of quantitative evidence that the low predictiveness, robustness, and replicability of biomedical research is at least partially related to quality deficits has exposed the lack of systematic approaches to improve and maintain quality in academia. We had to therefore design from scratch, implement and refine effective and transparent procedures for quality control in experimental neuroscience research. To the best of our knowledge, our QM system, which is certified according to DIN EN ISO 9001:2008, is now the first structured attempt to quality management in biomedical academic research in Germany, and possibly worldwide.

Among other features, our QM system features standard operating procedures (SOPs), common goals and indicators, communication structures and document management, critical incident management (LabCIRS), as well an electronic laboratory notebook. The ultimate goal of our QM system is to improve the reliability of our research and to change medical practice through novel guidelines or treatments. Due to the long cycle of the translation progress the further development of our QM system needs to at least partially be guided by surrogate indices, such as how many findings are successfully replicated, how many innovative discoveries are made, or how many clinical proof of concept studies were initiated based on our results, among many others.

References

Selection of articles coauthored by members of the Dept. of Exp. Neurology concerning research quality and translational success:

Llovera G, Hofmann K, Roth S, Salas-Pérdomo A, Ferrer-Ferrer M, Perego C, Zanier ER, Mamrak U, Rex A, Party H, Agin V, Fauchon C, Orset C, Haelewyn B, De Simoni MG, Dirnagl U, Grittner U, Planas AM, Plesnila N, Vivien D, Liesz A (2015) Results of a Preclinical Randomized Controlled (pRCT) Multicenter Trial: Anti-CD49d treatment for acute brain ischemia. Sci Transl Med (in press)

Duda GN, Grainger DW, Frisk ML, Bruckner-Tuderman L, Carr A, Dirnagl U, Einhäupl KM, Gottschalk S, Gruskin E, Huber C, June CH, Mooney DJ, Rietschel ET, Schütte G, Seeger W, Stevens MM, Urban R, Veldman A, Wess G, Volk HD (2014) Changing the mindset in life sciences toward translation: a consensus. Sci Transl Med. 6:264cm12

Dirnagl U (2014) Modeling immunity and inflammation in stroke: Can mice be trusted? Stroke 45:e177-8.

Schäbitz WR, Dirnagl U. (2014) Are We Ready to Translate T-Cell Transmigration in Stroke?  Stroke 45:1610-11

Kimmelman J, Mogil JS, Dirnagl U (2014) Distinguishing between exploratory and confirmatory preclinical research will improve translation. Plos Biol PLoS Biol 12(5): e1001863.

Dirnagl U, Endres M (2014) Found in translation - Preclinical stroke research predicts human pathophysiology, clinical phenotypes, and therapeutic outcomes. Stroke 2014; 45: 1510-1518

Macleod MR, Michie S, Roberts I, Dirnagl U, Chalmers I, Ioannidis JP, Al-Shahi Salman R, Chan A and Glasziou P (2014) Biomedical research: Increasing value, reducing waste. Lancet. 383:101-4.

Watzlawick R, Sena ES, Dirnagl U, Brommer B, Kopp MA, Macleod MR, Howells DW, Schwab JM (2014) Effect and Reporting Bias of RhoA/ROCK-Blockade Intervention on Locomotor Recovery After Spinal Cord Injury: A Systematic Review and Meta-analysis. JAMA Neurol. 71:91-9

Dirnagl U, Hakim A, Macleod M, Fisher M, Howells D, Alan SM, Steinberg G, Planas A, Boltze J, Savitz S, Iadecola C, Meairs S. A (2013) Concerted Appeal for International Cooperation in Preclinical Stroke Research. Stroke. 44:1754-60.

Dirnagl U, Fisher M. International, multicenter randomized preclinical trials in translational stroke research: It's time to act. (2012) Jointly published in Stroke  43(6):1453-4 and J Cereb Blood Flow Metab. 32(6):933-5.

Prüss H, Kopp MA, Brommer B, Gatzemeier N, Laginha I, Dirnagl U, Schwab JM.Non-Resolving Aspects of Acute Inflammation after Spinal Cord Injury (SCI): Indices and Resolution Plateau. (2011) Brain Pathol. 21:652-60.

Dirnagl U, Macleod MR. (2009) Stroke research at a road block: the streets from adversity should be paved with meta-analysis and good laboratory practice. Br J Pharmacol. Aug;157(7):1154-6.

Macleod MR, Fisher M, O'Collins V, Sena ES, Dirnagl U, Bath PM, Buchan A, van der Worp HB, Traystman R, Minematsu K, Donnan GA, Howells DW. (2008) Good Laboratory Practice. Preventing Introduction of Bias at the Bench. Stroke. 40:e50-2

Macleod MR, van der Worp HB, Sena ES, Howells DW, Dirnagl U, Donnan GA (2008) Evidence for the efficacy of NXY-059 in experimental focal cerebral ischaemia is confounded by study quality. Stroke 39:2824-9

Crossley NA, Sena E, Goehler J, Horn J, van der Worp B, Bath PM, Macleod M, Dirnagl U. (2008)  Empirical evidence of bias in the design of experimental stroke studies: a meta-epidemiological approach. Stroke 39(3):929-34

Contact

Claudia Kurreck

Qualitätsmanagement-
beauftragte
Abteilung für Experimentelle Neurologie
Charite Universitätsmedizin Berlin

Phone: +49 (0)30 450 560 664
E-Mail: Quality Management

Certified

The Department of Experimental Neurology is fully certified according to ISO 9001 (Quality management).