Table 5 Quotations illustrating design-related factors

You know, in every study you have the problem that if you look on your emotionally coloured experiences then you mean, ‘Oh, I think from our 2000 patients with disease X, we will have per year a minimum of 100, which can be a part of a trial.’ And then you know, 50% will have no interest to be a member of a clinical trial. ‘Okay we will have 50’. But that’s only possible if everybody in your team has the same motivation as yourself and that’s the problem. And so you see, half of the patients you have no direct contact, despite the situation that I am the chief of the department. And so it’s really a problem of too optimistic view on the clinical basis of your study. T10 Principal Investigator of a discontinued trial

Everybody knows that the sites will always overestimate their recruitment. But they do it (feasibility assessment) once in the beginning of the study and they base their plans on what the sites say. And then they run into these troubles. And they often don’t repeat the feasibility. If the sites are behind, they are not meeting the targets they said in the beginning, you would ask them again: ‘Ok well you didn’t give us 50 patients, you have 5, can you give us the new plan of what you can actually achieve, now that you have some experience with the study?’ And they would then update their feasibility on an ongoing basis and know exactly where they stand against what is realistic, rather than, you know, wishful thinking. R6 Representative of pharmaceutical industry

Well, first there is a certain level of optimism, of undue optimism on the part of the researchers. They figure that if these patients come to the hospital; they would be able to recruit them. They don’t necessarily think about what happens at night, during weekends, when the staff maybe goes on vacation, maybe they are not caught when they should be, there will be a good amount of opportunities missed for recruitment. They don’t think about that in advance. And if they do, they underestimate the patients that will be missed during the process. R25 Representative Clinical Trial Unit

…the second point is wrong assessment by investigators and overestimate of the ability to recruit. My own experience with that – I worked many years in an outpatient department with patients and I participated in quite a large number of studies there were situations where I completely (emphasis in original) overestimated my ability to recruit. Oh I thought, yeah no problem I have seen just so many of patients last year here and it happens that from that day onwards there was no patient fulfilling requirements anymore. Just happens! About half a year nothing. R30 Representative of pharmaceutical industry

The major difficulty usually is the… the exclusion criteria and very tight inclusion criteria. So people are so… let's say, so concerned about having no (…) well, not only confounding factors but also no side effects. So they prevent all patients who could potentially have side effects and they try to exclude them before, which makes it more difficult for us to find exactly the patients… You know, they want to kind of have healthy patients without failure (laughs). Or healthy patients with chronic kidney disease which is relatively rare or healthy diabetics. T4 Principal Investigator of a discontinued trial

But when you are doing a pilot or feasibility, the sites are handpicked, so these are the keeners, these are not the lagers, it is the people who can recruit and who will recruit and do a good job with it and we feel very strongly that everybody who is eligible for that study should be in that study. We go over and above to make sure that this is going to happen. When we do a pilot, the recruitment rates are estimated but it is the keeners who do that (however that might not be the case of all centers which will be eventually included in the trial). T1 Research coordinator of a discontinued trial