1. 1. Evaluating Translational Research:A Process Marker ModelWilliam Trochim , Ph.D. , Cathleen Kane ,M.P.A., Mark J. Graham, Ph.D. , andHarold A. Pincus , M.D.
2. 2. What is Translational Research? Translating knowledge gained from laboratoryscience into clinical practice to improve health Focus is on the integration of activities frombench to bedside.
3. 3. The aim of translational research is toproduce new:TherapeuticsMedical devicesTools for diagnosing diseaseAvenues for community engagement research
4. 4. The Translation ContinuumSource: National Cancer InstituteBasicScientificDiscoveryEarlyTranslationLateTranslationDissemination AdoptionPromisinggeneBasicepidemiologicalfindingPartnershipsInterventiondevelopmentPhase III trialsRegulatoryapprovalPartnershipsHealth servicesresearch tosupportdisseminationand adoptionTo communityprovidersTo patients andpublicAdoption ofadvance byproviders,patients, andpublicPaymentmechanisms toenable adoption
5. 5. The National Institutes of Health (NIH) havemade it a central priority, part of theirRoadmap initiative. One of their primary programs, the Clinical andTranslational Science Awards (CTSAs) 350 million per year to fund 55 research centers In 2012 - fund 60 centers at a cost ofapproximately a half billion dollars per year,making it the largest program at NIH
6. 6. One of the most significant motivations comesfrom a relatively small number of studies thatshow that it takes a long time to move basicscientific ideas to practice and health impacts It takes an estimated average of 17 years foronly 14% of new scientific discoveries to enterday-to-day clinical practice
7. 7. This time lag is seen as too long, certainly longerthan necessary Must be a better way to move research to practicemore quickly without sacrificing quality orincreasing costs. Proposed solutions include everything from better management of scientific research increased process efficiency wholesale rethinking of the biomedical research-practiceendeavor for the 21st century.
8. 8. Models of TranslationalResearch
9. 9. Westfall et all
10. 10. Dougherty and Conway Feedback loopsBroader setting overtime
11. 11. Khoury et allResearch that describes, interprets and predicts the impact of variousinfluences, especially (but not exclusively) interventions of final endpointsthat matter to decision makers
12. 12. Translational Research ModelSynthesis
13. 13. Multiple competing models Different and conflicting numbers anddefinitions of translational research phases Complicate communication about translationalresearch generally Risk of confusing interpretations ofevaluations
14. 14. The particular dilemma for translational researchevaluators translational Tower of Babel Same phase label is used for very differentoperational stages in the research practicecontinuum, makes cross-evaluation comparisons and synthesesespecially problematic.
15. 15. First, and perhaps most important, all of themcharacterize translational research as atemporal process moving from basic to clinicalto postclinical research and ultimately to useand public health impact All of them also incorporate the idea ofbidirectionality
16. 16. Second, the three alternative models to Sunget al.s T1/T2 model differ in how finely theydivide their T1 and T2 phases.
17. 17. Westfall et al. believe that practice-basedresearch needs to be highlighted Dougherty and Conway want to be sure to note thedistinction between efficacy and effectivenessstudies in clinical contexts Khoury et al. want to preserve the efficacyeffectiveness distinction and make one betweenoutcomes research and other types ofpostguidelines work
18. 18. Leading to ever more complex models, andcontradictory classification schemes
19. 19. Third, all of the models make a basicdistinction between research that takes placebefore and after the development ofsynthesized clinical trial knowledge at thepoint of demarcation between T1 and T2. This distinction between pre- and postclinicalsynthesis may represent a critical jump fromindividual clinical studies (before) to moresynthesized general knowledge that cutsacross studies (after).
20. 20. A General Framework forTranslational Research and ItsEvaluation
21. 21. Process marker model, characterized by the twocomponents that constitute its name.
22. 22. First, it views translational research as acontinuous process that moves from basicresearch through clinical, postclinical, andpractice-based research and ultimately tohealth policies, outcomes, and impacts. Process may be bidirectional, variable, andcomplex
23. 23. Second, it assumes that there are many differentpotential markers along this process.
24. 24. The focus in this model identifying a set of observable points in the process that can be operationally defined and measured to enable evaluation of the duration of segments ofthe research-practice continuum.
25. 25. Model assumes that one would define a numberof operational markers along a presumedprocess continuum. Assuming that all of the markers use a commonmeasurement scale (e.g., dates), it is thenrelatively easy to operationally define thedifference between any two markers as theduration of time between their dates.
26. 26. What is the correct operational marker touse? A simple answer is that there is not a singlecorrect markerdifferent markers simplyrepresent different reference points in anassumed continuous process. That said, some markers may be better thanothers for different purposes and in differentcontexts
27. 27. Another consideration is that some markersare likely to be encountered by more protocolsthan others. Since protocols can take different pathways inthe process of translation, one would generallywant to select markers that are more likely tobe commonly passed
28. 28. Another consideration is that there are likelyto be subprocesses that get repeatedthroughout the overall translational process. For instance, the subprocess of conducting,replicating, and using a research study followsthe same basic steps regardless of whether itis a basic, clinical, or postclinical study Look at the durations between two steps inthis subprocess
29. 29. Characteristics that commend the process markerframework over multiphase models: Avoids theoretical presumptions and undefinedabstractions Emphasizes observable measurable phenomena,allowing anyone to readily see how any marker isdefined Avoids the debates about how many phases thereare in translational research, while enablingevaluators to use phased-based approaches as longas they operationally define what they mean.
30. 30. Encourages replicability Robust and forgiving ie, missing data andvariable protocol pathways can beaccommodated Encourage development of new hypothesesthat involve more precise operationaldefinitions
31. 31. Avoids debates about the scope oftranslational research ie, the scope oftranslation being examined in any given processmarker evaluation is simply the process that isencompassed between the first and lastmarker measured Applied prospectively or retrospectively
32. 32. The process marker model is firmly rooted in aprocess modeling research tradition in biomedicalresearch as well as in other fields such as qualitycontrol and assurance
33. 33. Important features of this approach Evaluate translational research at any level ofscale Provides a foundation for the evaluation ofinterventions designed to improve translationalresearch and the integration of these findingsinto a field of translational studies
34. 34. The process marker model provides a commonframework that can link these many and variedstudies together Assess whether such interventions contribute toreducing time to translation
35. 35. Important challenges May lead to complex and difficult tocommunicate models of translational research Relies upon descriptive statisticssuch asmedian durationsas the heart of the results
36. 36. Increased application of an operational processmarker approach to the study of translationalresearch is likely to lead to considerableevolution and adaption over time. The field will be able to determine empiricallythe degree to which various markers arefeasible to measure and yield results that havevalue for our understanding of translation
37. 37. Conclusion Translational research is critical to the evolutionof biomedical research and practice in the 21stcentury The key problems that led to its emergencetherelatively long time from discovery to use andimpactand the relatively low proportion ofdiscoveries that survive that journeyremain achallenge Significant investments in translational researchare already being made
38. 38. Evaluation will be essential for managingtranslational research effectively, learningwhat works and what does not, and beingaccountable for these investments The current state of conceptual models anddefinitions of translational research posessignificant challenges to our ability to evaluate
39. 39. There is considerable disagreement aboutmany of the key characteristics associatedwith translational research Translational research involves movement alongthe research-practice continuum, ultimately tohealth impacts.
40. 40. It is clear from that the unit of translationthe thing that is being translatedcanchange dramatically across the span of theresearch-practice continuum While there is also wide acceptance that theend point of translational research isultimately in health outcomes and impacts,many of the translational research activitieswill not directly touch on health impacts
41. 41. Stay with the data in the form of operationallydefinable markers (measures) on the pathwaysfrom basic research to health impacts. If multiphase classification systems are used inevaluations, indicate clearly whose definition ofphases are employed and how the different phasesare being operationalized. In the meantime broader translational researchcommunity to collect feedback regarding variousevaluation measurement challenges
42. 42. Thank You ..