Comment Implementation Science – “new kid on the block” and what to expect from it. Serhiy Souchelnytskyi Nerocentrum, Karolinska University Hospital, Stockholm, Sweden Oranta CancerDiagnostics AB, Uppsala, Sweden Email:
[email protected]
In the last years, the term “Implementation Science” has entered the medical vocabulary. As a newcomer, implementation science attracts a number of questions. What is the subject of implementation science? How does it differ from already established fields of medicine? What to expect from implementation science? In this letter, I would like to raise discussion about place of implementation science in the process of introduction of fundamental research into clinical practice. Recent publications tend to limit implementation science to observations and making recommendations. I believe that implementation science should be also pro-active and identify and promote practices of the future health care, and not only observe existing practices. According to the NIH-supported definition, implementation science “addresses the level to which health interventions can fit within real-world public health and clinical service systems”. This quite broad definition indicates study of all aspects of transferring research findings into clinical practice. It has to be noted that translation of ideas into accepted routine in a clinic has had many different names. Pre-clinical research, translational research, 1
comprehensive centers, clinical trials, integrative medicine, and now implementation medicine, are only some of them. Coming up with new names is not a bad thing, as it renews interest to the important issue. Translation of research developments into routine clinical applications goes via a number of steps (Figure 1). These steps start with discovery of novel treatments and drugs, pre-clinical validation studies to adjust the discovery to the requirements of clinics, clinical trials-type studies, development of programs for application of treatments in clinics, follow-up of outcomes, and evaluation of the impact of novel treatments on the society. The “death valley” in introduction of novel findings has been pre-clinical and clinical validations and introduction of approved drugs and treatments in clinical practice. Would implementation science help in the voyage through this death valley? Implementation of novel drugs and treatments would require passing all the steps shown in Figure 1. However, implementation science tends today to focus on the observation aspect, with the main output to be recommendations on the use of drugs and treatments. Observing existing activities and making recommendations is an important work. However, the stronger impact may be achieved if the implementation science would include development of mechanisms strongly stimulating collaboration between healthcare providers (Hospitals and their national managing organizations), research (Universities), policy makers (ministries of health), politicians, pharmaceutical industry, society groups, etc. Even stronger impact would be expected if implementation science would adopt a pro-active approach by searching for, attracting and shaping novel developments with potentially strong impact on the health care. Lack of the networking mechanisms and pro-active approaches may cripple efficacy of the observation-recommendation approach. An example of such failure is result of trials to implement some PARP inhibitors into clinical practice. When PARp inhibitor iniparib failed 2
in clinical trials with more than 280 millions USD of losses, it was a strong warning call. (http://www.bloomberg.com/news/2013-06-03/sanofi-ends-iniparib-research-plans-285million-charge.html). When the author of this letter tested iniparib (Figure 2), it become clear that the whole strategy of the implementation of iniparib in the clinical practice was too narrow. Academic research was not fully evaluated, clinical trials protocol did not include advanced companion diagnostics, and aspects of incorporation of the drug in the clinics and in the healthcare system were not carefully elaborated. Could implementation science help to avoid such a failure? I believe that ”Yes”, it could. If all aspects required for taking experimental results to a well functional clinical practice would be followed, as in Figure 1. It would be interesting to discuss different points of view on the implementation science, as it is obvious that this “new kid on the block” may spark enthusiasm and approaches to negotiate the “death valley” in bringing discoveries to the clinic. However, implementation science may also be limited to describing facts and analyzing existing strategies, and therefore with lower impact on progress of medicine than it could have if including more pro-active approaches. Does clinical community see a place for implementation medicine, and what the clinic wants from it? Will implementation medicine make an impact on shaping current and future healthcare policies? And the last, will implementation medicine direct fundamental research towards requirements of the real world? I finish my comments with these questions, and hope that answers to them will be coming from clinicians, policy-makers and researchers involved in making medicine better and more efficient.
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Figures
Figure 1. Schematic presentation of steps of introduction of novel discoveries into the clinical practice. The steps from discovery to the clinical routine are indicated. The top graph shows estimates of success in transition between the steps. Three areas of the introduction efforts are shown – observation-to-recommendation area, efforts to organize collaborative activities, and proactive efforts.
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Figure 2. Failure to include all components of importance for introduction of a drug into a clinic may lead to failure of otherwise good research. Inhibition of protein PARylation by iniparib was dependent on concentration of the drug and density of cells in culture. The figure shows results of testing activity of iniparib on protein PARylation. Note that even this single assay indicated that the success of the introduction of iniparib would require a comprehensive program with better pre-clinical validation and better analysis of consequences, including financial, for the healthcare system. Proteins from MCF7 human breast carcinoma cells were metabolically labeled with a radioactive precursor to detect [P32]poly-ADP ribosylated proteins, and were treated or not with iniparib as indicated. After treatment, total cellular [P32]PARylated proteins were detected after exposure in a phosphorimager. Images of PARylated proteins of cells at 2 densities and treated or not with iniparib are shown. Note that iniparib indeed inhibited protein PARylation (left panel; compare intensities of the signals in lanes), but changing cell culturing conditions resulted in iniparib-dependent selective increase of protein PARylation (right pane; note increase of the signal upon incubation with 1.0 microM of iniparib). In clinical trials, such differences could account for high variability in response of patients to the treatment.
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