Appendix 1. Q: Question, below each question the options that could be selected as answer are given.
| Q1 | Please select from the list below the option that best describes you or your affiliation: Pharmaceutical industry, Biotech, CRO, University, Consultant, Other |
| Q2 | What is the size of your affiliation: < 10, < 100, < 1,000, > 1,000 employees |
| Q3 | In which country are you based? Belgium, France, Germany, United Kingdom, Other (please specify) |
| Q4 | Have you or your organization ever conducted a clinical trial in early drug development with combined protocols, such as single dose escalation + food study? Combined protocol = umbrella protocol: protocol that combines more than one study element, such as single ascending dose plus food study or single ascending dose plus multiple dose
Yes, No |
| Q5 | If yes, how many combined protocols did you or your organization conduct within the last 5 years? 1 – 3, 3 – 5, 5 – 10, > 10 |
| Q6 | Please give 1 to 3 representative examples (multiple options can be selected here) SD, MD, food, DDI, age, gender, ethnic bridging, absolute and/or relative bioavailability, mass balance |
| Q7 | In which population did you conduct these clinical trials with combined protocols? Healthy subjects, patients, healthy subjects+patients |
| Q8 | Did you use adaptive elements in these combined protocols? Adaptive elements = the protocol includes elements of flexibility e.g. of dose, sample size, sampling time-points, measurements, or allows overlap of study parts
Yes, No |
| Q9 | If yes: Which? (multiple options can be selected here) Flexibility of dose, sampling and measurements, sample size; parallel or independent conduct of study parts |
| Q10 | Were there any issues with the adaptive elements used in these combined protocols? Yes, No |
| Q11 | If yes, please state the issues |
| Q12 | What happens if adaptive elements are used and changes are made? |
| Q13 | Does this need to be notified to the competent authority and/or the ethics committee? Yes, No |
| Q14 | If notification is required, do you consider this beneficial? Yes, No |
| Q15 | When changes by the use of adaptive elements are made is approval from the competent authority and/or the ethics committee required before these changes can be implemented into the study? Yes, No |
| Q16 | If approval is required, please give an estimate (weeks) how long this would take |
| Q17 | How many substantial amendments did you submit for these trials with combined protocols? None, 1, 2, 3, 4, > 5, > 10 |
| Q18 | If you compare the duration of studies within a combined protocol with the duration of the sum of separate protocols is there any difference? Yes, No |
| Q19 | If yes, which (estimate)? (multiple options can be selected here) No time saving, combined protocol took longer than individual studies, time saving of avoiding substantial amendment(s), time saving of avoiding standard regulatory submission, time saving of ethics review times for initial submissions; (for duration differences estimate in months) |
| Q20 | To which competent authorities did you submit a clinical trial application with a combined protocol? famhp (Federal Agency for Medicines and Health Products, Belgium); ansm (National Agency for the Safety of Medicine and Health Products, France); BfArM (Federal Institute for Drugs and Medical Devices, Germany); PEI (Paul Ehrlich Institute, Germany); Medicines Evaluation Board (Netherlands); Healthcare Inspectorate (Netherlands); MHRA (Medicines and Healthcare Products Regulatory Agency, UK); Other (Please specify) |
| Q21 | Which feedback did you receive from the competent authority to your clinical trial application with a combined protocol? Approval, refusal, deficiency letter; specify main deficiencies |
| Q22 | What are advantages of combined protocols in your opinion? |
| Q23 | What are disadvantages of combined protocols in your opinion? |
| Q24 | Do you have any comments on combined protocols? Please specify |
| Q25 | Would you like to add anything else? Please specify |