Declining to participate
The explanations given for declining trial participation could be divided into two distinct groups relating to perceived necessity and perceived risk. For one group (N = 6), respondents' explanations indicated a lack of necessity to participate in the trial, and were characterised by mentions of largely mundane problems (either trial-specific or more circumstantial) that nonetheless took priority.
Trial-specific explanations included concerns about the trial involving too much commitment or too long a duration, particularly for individuals at the upper end of the age range.
"I think it was too much of a hassle for me [...] and I thought well if it's not too serious, which might sound stupid, I'm not gonna bother... At the end of the day would it have been beneficial?" (P3.5, male, 58, declined trial)
"The thought of this going on for five years, seemed to me a long time, I didn't want to commit myself." (P3.6, female, 73, declined trial)
A procedural aspect of the trial was the focus of concern for two respondents - the blood tests conducted at the baseline appointment to measure serum cholesterol levels, which led to fear and discomfort in these two, and thus to their declining to participate.
"Well the nurse said I was a fraction over and I could go on the trial. I said I didn't mind that but they was gonna take some blood from me. And I says, 'no way!' That was it. Because I'm terrified of needles" (P3.11, female, 73, declined trial)
Circumstantial explanations emphasised issues such as unfortunate timing due to unrelated health problems at the time of recruitment:
"I was happy to take part in it, but unfortunately I was in [the hospital] having problems and that's why I didn't take part, and I was going to see a specialist and there was a possibility it was either a- well they thought- a hernia, or an ulcer, so I spoke to my own doctor and he said obviously not to take part in this until we'd sorted the other problem out." (P3.2, female, 62, declined trial)
A few reported not seeing any personal benefits or incentives to participate in the trial, with one mentioning lack of financial incentive.
These largely mundane reasons had overridden any initial desire to take part in the trial. The priority of these reasons, and the lack of perceived necessity to participate (for example, "it's not too serious", P3.5), demonstrated the lack of risk perceived from the ankle brachial index result for these respondents.
In contrast, the second group (N = 5) were characterised by a high level of risk perceived from participating in the trial. For three respondents this translated into an unwillingness to accept the blinding and random allocation in the trial, and most importantly the possibility of being allocated to the placebo. One respondent disliked the idea of being a 'guinea pig' and acted on this by requesting aspirin on prescription from his own general practitioner, while one respondent chose the less formal route of self-medicating with over-the-counter aspirin.
"I tried to analyse what you were offering under the aspirin trial and when I found out you knew I was at risk, but you were prepared to put me on a dummy pill I said, get lost! And [...] they can't tell you what you were on. So I walked out of the trial at that stage and I went to my own doctor... I spoke to him and told him what was happening, and he said, 'Do you want to go on aspirin?' and I said, 'Well it sounds like I might have to. I'd sooner be on it rather than nothing.' So I have the 75 mg aspirin." (P3.8, male, 68, declined trial)
"I buy [aspirin] in Superdrug, and I just take one you know dissolved in water most days, maybe five times a week" (P3.10, female, 61, declined trial)
For two respondents the risk they perceived from aspirin led to their declining. Despite being keen to participate, one man had previously experienced adverse reactions to aspirin, and thus stated that he would have participated if he could have been guaranteed to receive the placebo.
"they had said in the letter it was aspirin...I thought well I'll go and see er...I get tummy trouble, so I try to avoid aspirin if I can [...] and I didn't really fancy going on a prolonged sort of dose of it. So that was the main reason I didn't go on the trial. [...] I said, 'well I don't really want aspirin', [thinking that] they might just give me the placebo, but to some extent the trial's not really working properly if I go in and say, 'well I don't want aspirin but I'll go on the dummy'" (P3.1, male, 59, declined trial)
A second respondent who declined in order to avoid aspirin reported a long history of adverse reactions to various medications and now sought to avoid all conventional medication. For her this avoidance included the placebo:
"I thought, no I'll try and take care of myself other ways [...] I take supplements, I'm also vegetarian anyway, so I thought I would increase my fruit and veg, I take oils, I read a lot of health supplements, I also attend an Ayuverdic doctor. [...] I didn't know what was in the dummy pill! The placebo, I didn't know what was in that, so I wasn't willing to swallow it [either]." (P3.9, female, 60, declined trial)
In comparison to the first group, the risk perceived by this second group was associated with a perceived necessity to engage in action of some sort - seeking aspirin or identifying other lifestyle behaviours with the aim of minimising the risk associated with their ankle brachial index result.
Stopping trial medication
For the respondents who had started to participate in the trial but had stopped the medication, their explanations for stopping fit into four main categories: Side effects attributed to the trial medication; starting a course of aspirin or medication contraindicated to aspirin; experiencing an outcome event [
13]; and 'changed mind'.
Seven respondents described side effects they had experienced and had attributed to the trial medication. They reported consulting the trial team or their own doctor, and being advised to stop the trial medication, either temporarily or permanently. Side effects ranged from knee swelling to tongue tingling, but the most typical were gastro-intestinal as discussed by focus group participants:
FG2.4: again I found that I had stomach problems with the tablet so I assumed that it must be the aspirin (yeah) I was taking it and I kept saying, 'I can't be ill, I don't even know what it is.' I stopped it and started it on two occasions and did find that I was waking up at night with a slight gnawing feeling in the stomach and
FG2.2: I was exactly the same
FG2.4: Did you have the same? Well that's good to know yeah
(FG2.4: female, 63; FG2.2: female, 61)
No respondent expressed anger in relation to these side effects (even when probed in the interview) or reported regret for participating despite the effects being severe in some cases:
"I really felt I'd got gall bladder trouble again because [the pain] was from here right through into me kidneys and really severe. So I went to my GP, and she just checked round and said straight away, 'Don't take anymore, and ring [the trial] and tell them' [...]
HCE: so once you got it sorted out, how did you feel about the trial then?
I felt like well I've let them down, but at same time your health does come first and if that tablet aspirin were gonna kill me...!
HCE: did you feel angry for getting the symptoms that you got?
No, no, because you go into it and you do know what you're doing I mean that were it, it were just one of them things, there's some people as you know who've started with it and they've still no problem." (P2.3, female, 55, stopped medication)
Indeed this respondent's comment about letting the trial down and disappointment in having to cease full participation in the trial was shared by others (for example most of the focus group participants). Furthermore, one respondent's disappointment about having stopped led him to contact the trial with the aim of restarting after a side effect-free period.
Six respondents had been prescribed aspirin, or a medication contraindicated to aspirin, for a range of conditions. Again there was an indication of disappointment in some of these respondents, but rather than an emotional reaction it was typical for the respondent to simply describe what happened in a somewhat resigned manner, accepting the requirements of the changes to their health. For example:
"I took angina, and I went and I [came] off the trial
Husband: and you'd then to start taking aspirin, you didn't know whether you were on aspirin or the placebo under the trial
Aye, and so that's why I come off it, but we're now taking an aspirin a day." (P2.11, female, 76, stopped medication)
"It was the fatal type of malaria I had...I was all wired up the whole time I was in [hospital] and they discovered I had heart fibrillation... After that I'd to go on warfarin you see, so that's why I had to drop out because warfarin and aspirin just don't agree" (P2.5, female, 77, stopped medication)
One respondent had experienced a myocardial infarction eleven months into the trial, which was one of the AAA trial outcome events. Similarly to those who had experienced side effects he did not blame the trial, rather he seemed to be fatalistic about the event.
HE: So how did you feel about that, about going into the trial?
"I was glad in the sense that they found something that maybe, you know. You don't know if you're taking the real aspirin or the dummy aspirin, I felt in a sense that it was helping, you know, till I actually took the heart attack"
(Later in interview):
HE: Did it change how you felt about the trial after having the heart attack?
"In what sense, do you mean whether the trial contributed? I thought maybe the trial to me in a way highlighted it, [that] my heart was bad you know... No I didn't blame anything on the trial, no, I felt that after all if it was gonna do it, then it was gonna happen you know..." (P2.8, male, 63, stopped medication)
In contrast to the medical explanations presented so far, the final category of explanation can be classified as 'changed mind'. Examples of this included two respondents who initially reported stopping the medication due to forgetfulness, but later in their interviews revealed an underlying dislike of medication, as demonstrated in the two quotes from the following respondent at different points in his interview:
"The only reason I stopped was simply because I kept forgetting to take the tablets you know [...] I'm getting terrible forgetful. And I mean it would just be a sort [of] sham for me to say I've been taking it when I haven't, you know. I think trials are- they are good things you know..."
(Later in interview):
"If you're taking a lot, it knocks the hell out of your stomach. [...] Given the choice, I'd rather not take medication full stop." (P2.6 male, 55, stopped medication)
Two respondents explained the lack of necessity they attributed to taking medication associated with the lack of risk they perceived from the ankle brachial index (echoing one group of explanations for declining).
"I think if it had been medication that I needed to take, I would have taken it. And that sounds as though I wasn't committed, but I was when I started certainly, but you know I'd go to take them and 'goodness me, I haven't taken them this week'." (P2.4 male, 72, stopped medication)
These two respondents described managing without medication all their life and thus seeing no reason for starting now.
In this sample, respondents who stopped the medication due to changing their mind seemed to do so early on, whereas most of those who stopped for medical reasons had taken the trial medication for a longer period - up to 3 years in some cases - by the time that they stopped.