Background
Informed consent forms the cornerstone of ethical requirements in healthcare research [
1,
2]. In the context of healthcare research, the giving of informed consent signifies that an individual has made an informed and voluntary decision about their participation in a research study. Randomised controlled trials (RCTs) usually require all participants to sign an informed consent document indicating that they have understood the information they have been provided with before they commence participation in the trial [
1].
To assist in making an informed decision about participation, potential trial participants in the UK are provided with a patient information leaflet (PIL) that contains information about the RCT. The information included in PILs is guided by the Declaration of Helsinki, the International Conference on Harmonisation Good Clinical Practice (ICH GCP) and also by national guidance such as the National Research Ethics Service (NRES) [
1,
3,
4]. As defined by the guidance, the PIL should include, at minimum, information about: the purpose of the trial; procedures; interventions; possible risks and benefits; sources of finance; potential conflicts of interest; and the researcher’s affiliation [
1,
3]. The guidance for informational requirements covers predominantly fact-based information and is standardised at a population level [
1,
3].
Currently the PIL and consent form are the only components of the consent decision making process for RCTs that are formally regulated, through specific guidance, and reviewed by ethics committees or internal review bodies [
1]. However, as with decisions about treatment, potential participants vary in the amount of information they desire when faced with a decision about trial participation [
5‐
7]. As such, within a trial context where the information minimum has been pre-determined by the guidance [
1,
3,
4], many potential participants’ preferences for information may be exceeded [
6] and other approaches to supporting decision making may be required. Despite this, there is evidence that some trial participants, both those considering participation and those actively enrolled in clinical trials, fail to understand key components of the trial processes or rationale [
8‐
10]. This has ranged from misunderstandings about: risks [
11]; the right to withdraw [
11]; confidentiality [
12]; side effects [
13]; and purpose of the trial [
14]. This suggests that in the context of trial participation, existing approaches to information provision may be sub-optimal and some decisions may not have been based on a full understanding or consideration of all the relevant issues. This may be because the information is too complex or not designed to support an informed decision but rather to present factual information to the potential participant. A range of studies have explored ways of improving information, and have tended to focus on the content and structure of the information [
8]. For example: the length of the information sheet, that is, short versus long leaflets [
10,
15]; simplified or enhanced versions of the same PIL [
16,
17]; patient-specific information versus generic information [
18,
19]; linguistic analysis of leaflets [
20]; consumer involvement in development of PILs [
21]; audio-visual information [
22]; computer-based information [
23]; and user testing to improve content [
24].
As discussed above, the literature to date has tended to focus on the provision of information, to improve understanding about trial processes, with the aim of making the consent process more 'informed’. However, informed decision making in the context of trial participation is a complex process and requires more than just greater understanding or comprehension of certain fact-based information. For example, key considerations which are regarded by established theories of decision making as being important for making 'good’ decisions (for example considering the alternatives (for example standard care and what that is), making trade-offs and evaluating potential outcomes of the decision [
25]) might not be presented or discussed at all during the informed consent discussion or explicit in the PIL. These omissions may stem from the conventional conceptualisation of trial participation as an act of 'informed consent’. This conceptualisation likely relates to the ethical and regulatory requirements, rather than viewing deliberations and decisions about participation as broader and more complex [
26].
Decision aids have been developed for a variety of treatment and screening decisions as a means of improving 'informed decisions’ in particular contexts and across the decision making process [
25]. These decision aids provide information about: the available options and any associated outcomes; personalise information by including exercises to help patients think about what matters most to them; and provide ways of communicating this with the healthcare professional to reach a decision [
25]. There is substantial evidence to suggest that decision aids can positively influence outcomes, such as: improving knowledge, especially when there is clinical equipoise; providing accurate perceptions of outcome probabilities; and align preferred outcomes with the choice made [
25].
As discussed previously, the traditional conceptualisation of informed consent in RCTs is as a behaviour relating to understanding rather than promoting informed decisions. This may have led to the information contained within PILs being focussed on fact-based trial information rather than, for example, what trial participation might mean for that individual. Yet, these personal considerations do play a significant role for people when deciding whether or not to participate in a trial [
27] and this is often the type of information contained within treatment decision aids. As such, it is perhaps timely to re-think the way in which decisions about trial participation and discussions about informed consent are supported.
Preliminary studies exploring the potential of decision aids for use in the informed consent process for RCTs have shown promise in that they appear to improve aspects of the decision making process [
28‐
32]. Decision aids to support decisions about trial participation have been shown to be acceptable and valued by potential participants [
28,
29]. In these studies, the decision aid was a substitute for the existing PIL and contained all of the required information expected to be in a PIL in addition to those expected to be in a decision aid. Specifically, decision aids in this context have been shown to improve understanding about the trial and its associated interventions [
28,
29], produce low levels of decision conflict [
29] and not raise anxiety [
28,
29]. However, these studies had small sample sizes and were set within a hypothetical trial context. As such, the need for further research has been noted [
28‐
32]. A recent study examined the extent to which existing informed consent documents conform to standards for encouraging good quality decision making as laid out by International Patient Decision Aid Standards (IPDAS) [
33,
34]. The evaluation tool used in the study by Brehaut and colleagues contained two sections: a series of items derived from the IPDAS and a set of items derived from published guidance on informed consent [
34]. Only the first section of the tool, including items developed from the IPDAS, was used and the majority of the included PILs were developed in the US with approximately half being for cancer trials [
34]. Guidance for US PILs differs from that for UK PILs with regard to whether specific information is presented in either the information sheet or consent form, with UK consent forms being a one-page document, whereas US consent forms are longer and contain much of the information contained within the UK PIL. Moreover, the study by Brehaut and colleagues did not assess word count or readability, both of which can contribute to understanding of information and length of document.
Previous research has suggested that decision aids for trial participation have the potential to promote good quality decision making [
28,
29] and specific components of decision aids that have been applied in RCTs have also offered promise [
30,
35]. Therefore, this study aimed to assess the feasibility of assessing the extent to which items considered important in decision aids are present in existing UK PILs. We used the complete evaluation tool (developed by Brehaut
et al.[
34]), alongside word count and readability 'calculators’, to evaluate PILs across a range of clinical conditions in a UK context.
Discussion
This study evaluated PILs from UK RCTs using an evaluation tool based on the IPDAS [
33] and informed consent guidelines.
We assumed that all included PILs had been reviewed by an ethics committee and had been given a favourable opinion. Despite this, we found that the majority of PILs did not perform well using the tool (based on a score of less than 50%). All the PILs scored more poorly on Section A as compared to Section B. Our results provide an indication that information shown to support high quality decision making in other contexts is lacking in PILs for UK RCTs. There were four sub-sections in Section A that scored consistently poorly across all leaflets. These sub-sections were: presenting probabilities; clarifying and expressing values; structured guidance in deliberation and communication; and using evidence. This was not surprising given these concepts are not currently included in the informed consent guidance [
1,
4]. However, the items reflect standards that have been shown to be important to promote high quality decisions for treatment and screening [
25] and identify items that have also been shown to be important to trial participants during their trial participation experience [
27]. Moreover, our findings are mirrored in a similar study by Brehaut and colleagues, who also demonstrate an absence or lack of detail related to these items in PILs developed for trials in other contexts [
34]. Perhaps also unsurprisingly, in our study, scores for Section B were better than scores for Section A. This is perhaps because many of the items included in Section B are present within the current guidelines for informed consent documents [
1,
3]. Our findings suggest that the information presented in PILs to date has tended to focus on key elements of the RCT rather than supporting the process for decision making. As highlighted earlier, arguably this relates to conceptualisations of trial participation as being merely an act or a process of informed consent. As such, we propose reconsideration of the purpose of PILs and their role in the informed consent process. We would support a move to a more informed decision making process which encourages potential participants to assess what matters to them and how trial participation relates to them personally as individuals. This study provides further evidence that PILs do not include information that has been shown to improve decision making in other contexts. As such, this could suggest that poor quality decisions are being made about trial participation and indicates room for improvement.
There is evidence that some of the items identified as lacking from PILs, which were measured in Section A, may have an important role to play in decision making for participation in RCTs. For example, the section on 'presenting probabilities’ was lacking in most PILs, but aspects of this concept have been shown to be important for decisions about trial participation. In a recent study, parents were faced with a hypothetical decision about inclusion of their child in a RCT of paediatric postoperative pain control. Parents who received probabilistic risk information in pictograph form (a diagram that conveys meaning through pictorial resemblance) understood the information better than those who received information as words or tables [
35]. Also, exercises to help patients clarify and express their values, that is, to determine what matters most to them, have been shown to play a potentially important role in decision making for potential RCT participants [
30]. A recent study provided potential participants with values clarification exercises when considering participation in a hypothetical trial for breast cancer treatment [
30]. These exercises were found to be beneficial in this context as they enabled effective deliberation about the decision by lowering ambivalence and decisional uncertainty and improving the clarity of personal values [
30]. Such exercises were also identified as lacking in the PILs in this study. Lastly, another of the areas which scored consistently poorly across the PILs was structured guidance in deliberation and communication. This type of information could be incorporated by including text such as
' take time to think about how you would feel if you received treatment A rather than treatment B, and how the possible side effects of each would affect you personally’ and 'think carefully about your decision to participate and how it might impact on your life, take time to discuss with family and friends’, and so on. However, the impact and usefulness of such information requires investigation. To our knowledge there is no published research into using structured guidance in deliberation and communication within RCT PILs.
There was no correlation identified between readability and tool score. Interestingly, the average readability level of the PILs in this study (13 to 15 years) is well above the estimated reading age of the UK population in general (9 years) [
38]. It is worth noting that readability formulae (such as Flesch-Kincaid) have limitations in that they test 'structure and composition’ rather than meaning or context. In addition they do not take into account additional influences on 'readability’ such as layout, appearance, print size, and use of diagrams [
38]. However, there was a significant correlation between word count and tool score. This may be expected as longer PILs can incorporate more information and thus potentially score higher on the evaluation tool. We are not, however, promoting the lengthening of existing PILs, which have previously been noted as getting longer whilst not necessarily improving understanding [
39]. It is possible to write shorter PILs whilst improving the overall evaluation score and being in accord with current guidance from ethics committees, as evident from some of the PILs included in this study. For example, PIL01 and PIL17 (word count 1,500 to 2,000) scored higher than others containing substantially more words (PIL04 and PIL15 (word count 2,500 to 3,000)). It may be that the tool should include consideration of word count to accommodate any effect of the number of words in the PIL. Therefore, it may be helpful to develop a framework from the evaluation tool for those writing PILs for RCTs to encourage them to include text that might facilitate better quality decisions which are more aligned with promoting 'informed’ consent.
Strengths and limitations
The primary strength of this study is that it investigated the content of a sample of UK PILs, considering the extent to which they contained key information which is known to support decision making in other contexts. A further strength of the study is that each PIL was scored by two researchers independently, so as not to introduce rater bias. This study is the first to report the use of Section B of the tool which was developed with the specific aim of assessing consent forms in a US and Canadian context. As discussed earlier, consent forms for US trials are often considerably longer than those in the UK (where they are generally a single page) and much of the information contained within US consent forms would be found in a PIL in the UK. Therefore, we felt it was appropriate to use both sections of the tool to assess UK PILs.
We undertook this study as a feasibility study to assess whether the tool could be used to evaluate PILs from UK-based RCTs, and as such, our sample was small. Although taken from a convenience sample, PILs were sampled purposively to ensure that there was representativeness of CTUs (so as not to introduce any bias from developers) and intervention type across the sample. As we sourced only publicly available PILs from CTU websites, the number of PILs identified is likely to be much smaller than the number of RCTs on-going or recently completed in the UK. Moreover, CTUs may be selective with regard to which PILs they make publicly available on their websites. Despite these potential limitations, we found both variability in scores between PILs and consistency in terms of which sub-sections the PILs scored poorly on. This suggests that our findings may be generalisable, and have relevance to a wider range of PILs for UK RCTs. We restricted our sample to PILs dated from 2001 onwards (to align with the introduction of the European Clinical Trials Directive [
36]). Although it is possible that PILs written more recently may score better on the tool, partly because of updates to UK guidance [
4], we did not find evidence of an association between year of publication and tool score (r = -0.136,
P = 0.566). In addition, the majority of the PILs included in our study (16/20) were produced after 2006, and so are likely to conform to the most recent UK guidance documents [
4].
Key recommendations
As is evident from existing studies, changing the structure of information contained within PILs often has little or no effect on knowledge or understanding. However, the findings from this study support new ways of thinking about the information to include in a PIL, which may be more encompassing for supporting high quality decision making, and as such, more aligned with the process of 'informed’ decision making relating to consent. Therefore to improve decision quality with regard to making decisions about trial participation, it may be important to incorporate, or at least consider inclusion of, these items into PILs. The preliminary findings from other studies do offer promise for the use of decision aids, and associated aspects, within the context of informed consent for clinical trials [
28‐
30,
35]. We believe there may be potential benefit from the use of decision aids in this context. However, there is currently insufficient evidence to propose a definitive model to improve the existing process such that it aligns more with 'informed decisions’ for trial participation or to recommend writing PILs to IPDAS standards. At present, suggestions for researchers could be to evaluate their own PILs using the tool, equivalent frameworks developed from the IPDAS or explore those items identified in this study as lacking from existing PILs. Any areas which score poorly could be supplemented before the PILs are used in the informed consent process and piloted with potential participants to discuss support for decision making. However, before this could be implemented, empirical studies assessing whether any of these items are associated with an improvement in decision making are required.
It should be recognised that PILs form only one piece of the jigsaw for supporting decisions about trial participation and that decision making in this context is often influenced by much more than just the provided information [
27]. We propose that existing PILs need to be replaced, or supplemented, with interventions that are more suited to supporting informed decision making. This may be a decision aid but may also be a strategy for improved communication. It is worth noting that more informed decisions about participation in RCTs may impact either negatively or positively on both recruitment and retention within a study. We postulate that participants who are more fully informed at the outset and more aware of the likely expectations on them throughout their participation experience may be less likely to drop out, but this remains to be determined empirically.
Engagement with key stakeholders such as ethics committees, policy makers, patients and trialists could help to incorporate the findings from this research into the development process for PILs, and pave the way for new ways of thinking about supporting informed decisions in the context of RCT participation.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
KG conceived the study, carried out the analysis of PILs, contributed to data analysis and led the writing of the manuscript. WH carried out the analysis of PILs and contributed to data analysis. ZS and SC both participated in the design of the study and coordination and helped to draft the manuscript. JB developed the original evaluation tool. All authors read and approved the final manuscript.