1. Identifying and recruiting patients for clinical trials in the future: a pharma perspective Rob Thwaites EC/EFPIA Workshop on ” Primary and secondary use of EHRs: Enhancing clinical research ” 11 Oct 2007

2. Identifying and recruiting patients for clinical trials in the future: a pharma perspective  In the near future there are major opportunities for recruitment activities to become increasingly electronically integrated –To date largely paper-based (or electronically separate) –In the future, electronic integration will be key  An example: protocol assessments will be increasingly electronic –Protocol assessments are a major part of trial feasibility questions –A joint process in the future will be built upon shared or integrated electronic protocol assessments  The new approach to protocol assessments will change the interaction between the different participants: –There will be new roles, responsibilities and sharing of risks –How might other aspects of patient recruitment be affected, and what will be the impact on existing interactions?

3. Clinical trial activities today are typically either unconnected electronic activities or still paper-based tasks Typical overall process for a pharmaceutical company sponsored clinical trial Initiation and recruitment Analysis and reporting Need for specific CT identified in the development plan Concept protocol written Possible sites surveyed for estimates of eligible subjects Analysis plan agreed Clinical trial protocol, plan and budget finalised Trial registered Sites identified Approvals received Sites initiated and trained Subject recruitment programme undertaken Potential subjects identified; consent requested GP notified of subject participation Subjects screened Subjects entered into trial and allocated code Subjects follow requirements of protocol Data collected using CRF Subjects safety monitored Monitoring visits conducted Source data verification conducted Data (coded) brought in house by sponsor Study design and planning Study conduct Databases “cleaned” then locked by sponsor Data analysed by sponsor Final study report written by sponsor Results disseminated by sponsor and investigators

4. In the near future there are major opportunities for recruitment activities to become more electronically integrated Opportunities in recruitment in a pharmaceutical company sponsored clinical trial Initiation and recruitment Analysis and reporting Need for specific CT identified in the development plan Concept protocol written Possible sites surveyed for estimates of eligible subjects Analysis plan agreed Clinical trial protocol, plan and budget finalised Trial registered Sites identified Approvals received Sites initiated and trained Subject recruitment programme undertaken Potential subjects identified; consent requested GP notified of subject participation Subjects screened Subjects entered into trial and allocated code Subjects follow requirements of protocol Data collected using CRF Subjects safety monitored Monitoring visits conducted Source data verification conducted Data (coded) brought in house by sponsor Study design and planning Study conduct Databases “cleaned” then locked by sponsor Data analysed by sponsor Final study report written by sponsor Results disseminated by sponsor and investigators

5. Identifying and recruiting patients for clinical trials in the future: a pharma perspective  In the near future there are major opportunities for recruitment activities to become increasingly electronically integrated –To date largely paper-based (or electronically separate) –In the future, electronic integration will be key  An example: protocol assessments will be increasingly electronic –Protocol assessments are a major part of trial feasibility questions –A joint process in the future will be built upon shared or integrated electronic protocol assessments  The new approach to protocol assessments will change the interaction between the different participants: –There will be new roles, responsibilities and sharing of risks –How might other aspects of patient recruitment be affected, and what will be the impact on existing interactions?

6. Where protocol assessments are done currently, there are typically three distinct roles... Sponsor Runs initial protocol assessment Investigator Designs study Commissions initial protocol assessment Selects investigators etc. Analyst Conducts local protocol assessment Recruits patients etc.

7. Where protocol assessments are done currently, there are typically three distinct roles with two sets of interactions SponsorAnalystInvestigator Interactions 1. Study design protocol assessment: Do subjects for the study exist (in principle)? Sponsor provides draft eligibility criteria to Analyst Analyst conducts protocol assessment on general patient database 2. Study initiation protocol assessment: Do subjects exist at the proposed investigator site? Sponsor provides final protocol to potential investigator Investigator conducts survey/analyses charts/guesses number of potential subjects

8. With widespread availability of EHRs and skills in analysing the data, roles may change...requiring different interactions Sponsor Analyst Investigator Analyst NB This is one example of how roles may change: in this case the analyst roles are internalised

9. A joint process in the future will be based on shared or integrated protocol assessments Site investigator Sponsor Clinical Sponsor Analytics Site Analytics Draft Protocol Execute PA Validate codes Deliver report Adapt codes Run local PA Deliver report Advise on local feasibility Finalise Protocol Finalise PA, codes and report Refine PA Deliver report Develop recruitment proposal Recruitment proposal accepted? PA = protocol assessment

10. In this example, how might interactions change, and what practical steps can we take?  Changing interactions (examples) –Sharing information between sponsor and potential investigator Protocol assessment together with the coding and detailed analysis –Lower, and better shared understanding of risks associated with recruitment –Bringing potential investigators into early design discussions? –Changing need for Analyst role (may be internalised) –Growth in Analyst role – sharing data, analysis and judgement with sponsor –Resource synergies – analyses can be adapted very quickly  What practical steps can we take? –Commit to sharing protocol assessments (and coding etc) with potential investigators –Raise awareness of value of protocol assessments within pharma and other research bodies –Press data vendors to access (and make available) relevant data –Support work of the Filtered Query group under HL7