Introduction

Patient-reported outcomes (PROs) are increasingly used in clinical trials to assess the impact of a medical treatment or intervention. PRO assess a range of outcomes including symptoms, functional health, well-being and psychological issues from the patients’ perspective, without interpretation by a clinician [1,2,3]. Between 2007 and 2013, 26,337 (27%) of the clinical trials registered on ClinicalTrials.gov included PROs [4]. However, there is growing evidence that there is substantial research waste in relation to PROs [5, 6]. A recent systematic evaluation of oncology clinical trials determined that PRO protocol items were frequently omitted, non-reporting of PRO trials results was common and PRO publications were considerable delayed and presented suboptimal standards of reporting [5]. Thus, important PRO evidence may not be available to benefit patients and society.

Assessing the impact of research is a complex activity; however, it is important that the impact of PRO data is understood as this may inform funding allocations and demonstrate accountability to government, stakeholders and society [7]. Impact is defined as “any identifiable benefit to, or positive influence on, the economy, society, public policy or services, culture, the environment or quality of life …” (p.26) [8]. A number of reviews describe potential pathways (i.e. “a way of achieving a specified result; a course of action’ [9]) to general research impact [8, 10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33]. However, few studies have investigated the optimal pathway or methods for augmenting or evaluating specific impacts of PRO trial data or the extent to which PRO impact is being realised. It is also not clear which is the most appropriate way to measure PRO impact, or the barriers and facilitators to realising that impact.

One way of assessing real-world impact is via the United Kingdom (UK) Higher Education Funding Council for England Research Excellence Framework (REF) impact case studies. During the REF 2014 exercise, UK higher education institutions submitted impact case studies: narratives that described the impact of research conducted during a specific time-period, including a number of case studies describing clinical trials involving PROs. REF case studies present meaningful, far-reaching and properly articulated impact that is demonstrated through convincing evidence. The impact presented focuses on the benefits of the research rather than on the pathways of research impact, allowing the assessment of real-world impact on society [34]. Examination of these case studies can enhance understanding of the best methods for maximising and measuring PRO research impact, not only in the UK, but also internationally since a number of the studies described in REF are international studies [10, 35].

Therefore, the study had four objectives. First, to conduct a systematic review of the literature to: i) determine the range of potential impact that may arise from clinical trial PRO clinical trial data, ii) identify potential PRO impact metrics iii) identify barriers/facilitators to maximising PRO impact and; iv) to examine REF 2014 impact case studies to explore real-world evidence of PRO trial data impact.

Methods

This systematic review was registered on the PROSPERO database (CRD42017067799) and results are reported in accordance with PRISMA guidelines [36].

Search strategy

Systematic review

Two reviewers (SCR and OLA) systematically and independently searched MEDLINE (Ovid), EMBASE, HMIC and CINAHL+ databases (inception to December 2018) for articles discussing the impact of PRO data collected from clinical trials from inception to December 2018 (see Additional file 1 for the full search strategy). The authors (SCR/MC/DK) designed the search strategy with input from a University of Birmingham Information Specialist. In addition, the keywords ‘patient reported outcome measure*’, ‘PROs’, ‘PRO’, ‘PROM’, ‘PROMS’, ‘HRQOL’, ‘HRQL’, ‘quality of life’, ‘impact’ and ‘clinical trial*’ were searched on Google Scholar, where the initial 100 results were screened. Only the first 100 results (10 pages) were revised, as article relevance diminishes with each page of results [37]. Lastly, additional publications (n = 3) were sought through communication with methodological PRO experts facilitated by MC/DK. Hand-searching of reference lists and citation searches of the included publications was also conducted to identify additional relevant articles.

REF 2014 impact case studies

The keywords “trial*” and “quality of life” or “patient reported outcome*” were introduced in the REF 2014 database. The search strategy was restricted to: i) Unit of assessment: main panel A (see Table 1 for further detail), ii) Summary impact type: ‘health’ and iii) Research subject area: medical and health sciences.

Table 1 REF 2014 – Main panel A
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Eligibility criteria

Systematic review publications were deemed eligible if they discussed research impact in the context of PRO clinical trial data. In particular, we sought information on the types of impact (and pathways to impact) thought to be associated with PRO findings, proposed methods for measuring such impact and perceived barriers/facilitators to generating PRO-specific research impact. Publications were excluded if: i) solely focused on PROs used in routine clinical practice as the focus of this review was on the proposed PRO impact from trials; ii) trial publications reporting PRO results as the focus was research impact rather than primary results; or iii) conference abstracts. REF 2014 impact case studies were eligible if they included a trial in which PRO data were collected. There were no language restrictions.

Data screening

Systematic review

The screening process was conducted independently by two reviewers (SCR and OLA). Citations were downloaded into Endnote® software (version X7.3.1) and duplicates deleted. Records were screened by title and abstract. Potentially relevant articles were identified for further full-text screening (SCR and OLA). Discrepancies were resolved through discussion with a third reviewer (MC/DK/AS) if required.

REF 2014 impact case studies

The screening process was also conducted independently by SCR and OLA. The case studies were downloaded into a Microsoft Excel spreadsheet. Records were screened by title and summary of the impact. Relevant case studies were selected for further full-text screening (SCR and OLA). Discrepancies were resolved through discussion, with a third reviewer (MC/DK/AS) as necessary.

Data extraction/coding

Systematic review

Data extraction was done after the final selection of the included articles. SCR and OLA independently identified text excerpts that provided information on PRO-specific impact types, pathways, metrics, barriers or facilitators from the systematic review. Both reviewers independently imported text excerpts into a qualitative data analysis software package (QRS NVivo 11). They generated categories independently using descriptive coding under the directed content analysis framework [38]. The ‘pathways to research impact’ framework [10] was deductively applied to the data in order to identify types of impact and impact metrics. Data which did not fit within the existing framework were added to a ‘miscellaneous’ category. ‘Influence on policy-making’ was the only impact category discussed by the articles included in the systematic review. Subsequently, the data coded into this impact category was organised into subgroups. Through deductive coding, the following types of impact were identified: ‘inform clinical practice’, ‘inform clinical guidelines’, ‘inform clinical decision-making’, ‘inform health policy’ and ‘inform shared decision-making’.

Inductive coding was undertaken to describe and interpret more detailed codes within the ‘influence on policy-making’ and miscellaneous categories. The following types of impact were identified through inductive coding: ‘support drug approval’, ‘support pricing decisions’, ‘support reimbursement decisions’ and ‘inform consent for treatment’. In addition, inductive coding was used to identify further impact metrics, and barriers and facilitators to PRO trial impact. Development of overarching themes occurred after the coding process and collation of codes. The following details were also extracted from all the included publications: author, publication year, journal, methodology, study focus and type of PRO data impact.

REF 2014 impact case studies

Deductive and inductive was also undertaken to identify types of impact, impact metrics and barriers and facilitators among the REF case studies. In addition, the following details were extracted from the REF 2014 case studies: name, submitting institution and clinical area; trial name and year of publication, trial design, leading study centre, trial phase, trial primary and secondary outcomes, PRO instrument, significance of primary and secondary trial outcomes and type of impact. Furthermore, type of impact was further classified as either: i) direct PRO impact, where there was evidence of a direct link between PRO trial findings and subsequent impact. ii) Indirect PRO impact, where a trial including PROs subsequently led to impact, but it was not possible to directly attribute this impact to the PRO findings over and above the other trial outcomes; or iii) no evidence of PRO impact, where a trial including PROs failed to lead to impact. SCR and OLA independently piloted the coding frames, following discussion with MC/DK/AS/CM to resolve discrepancies. Finally, systematic review and impact case studies coding frames were validated by the co-authors MC/DK/AS/CM, who possess expertise in PRO clinical trial data, research impact and qualitative data analysis.

Results

Systematic review

Included studies

The search strategy retrieved 11,377 citations from MEDLINE (Ovid), EMBASE, HMIC, and CINAHL+; 100 citations were returned using Google Scholar and 6 through expert communication (PRISMA flow diagram, Additional file 2). Eight thousand eight hundred seventy-seven citations were excluded following review of title and abstract. In total, 32 full-text publications were assessed. Sixteen articles were excluded at this stage, as they assessed PRO data in routine care as an intervention. An additional 23 articles were included following hand-searching of reference lists and citation searches. In total, 39 eligible publications were included in the synthesis.

Study characteristics

The characteristics of the 39 included publications are summarised in Appendix 1. Fifteen (38%) publications were classified as systematic reviews, 11 as literature reviews (28%), eight (20%) as commentaries, three as qualitative studies and two as guidance papers. Non-English publications were identified through the different bibliographic methods used.

PRO impact types and pathways to impact

The included publications identified nine types of impact that authors proposed could be associated with PRO trial findings. These included; ‘informing clinical practice’, ‘informing clinical guidelines’, ‘informing health policy’, ‘supporting drug approval’, ‘supporting pricing decisions’ and ‘supporting reimbursement decisions’, ‘informing clinical decision-making’ and ‘informing shared decision-making’ and ‘informing consent for treatment’ (Fig. 1).

Fig. 1
figure 1

Proposed PRO impact types

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The majority of publications (69%) focused on the potential impact of PRO trial results on clinical decision-making [7, 39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67]. Clinical decision-making refers to the clinical evidence-based decisions made regarding individual patient care by the clinicians whilst considering clinician’s knowledge, skills and attitudes, resources available and the patient’s own concerns, values and preferences [68]. 15% of the publications considered the benefits of using PRO trial results to inform clinical practice [53, 56, 62,63,64]. Clinical practice refers to the healthcare services provided to patients at an organisational level, which are normally adopted following clinical practice guidelines [69].

One paper focused on the impact of PRO trial results on clinical guideline development [46] and one paper focused on PRO data use in the development of healthcare policy [7]. Several publications recognised the impact of PRO trial findings on drug approval (29%) [49, 66, 70,71,72,73,74,75,76], pricing (7%) [61, 72, 77] and reimbursement decisions (20%) [7, 65, 66, 72, 75, 77, 78]. Eight publications (20%) discussed the influence of PRO data on pharmaceutical labelling claims by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) [49, 66, 70,71,72,73,74,75,76]. An example given by one author was ruxolitinib (Jakafi™): an oral inhibitor to treat intermediate or high risk patients with myelofibrosis. This was the first FDA approved oncology drug that used PROs as an endpoint and followed FDA guidance to support a PRO-based labelling claim [78]. The oncology drug was approved based on reduction in spleen volume and improvement in symptom severity (e.g. weight loss, night sweats, itching, abdominal pain/discomfort, bone pain, cough, inactivity, early satiety and fever), as measured by the Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 Total Symptom Score.

Lastly, one paper discussed the impact of PRO data on shared decision-making [79] and two papers (2%) on informing consent for treatment [44, 54]. The types of potential PRO impact proposed in each publication are summarised in Fig. 1 and described in Appendix 2. Shared decision-making is also important and four publications outlined the potential benefits of including PRO findings alongside other outcomes such as survival. This allowed patients and their clinicians to make an informed joint decision about treatment preferences and symptom management based on mutual understanding of treatment objectives and expectations [1,2,3,4].

PRO impact metrics

Based on the review of the 39 included publications, two impact metrics were identified. Number of pharmaceutical labelling claims approved, mentioned by eight authors [70,71,72,73,74,75,76, 80] and number of promotional labelling claims, discussed by one author [70].

Barriers to impact

Authors identified different perceived methodological barriers to PRO trial impact, which fell within the following categories: ‘trial design’, ‘conduct and analysis’, ‘reporting’ and the ‘use of PRO data in practice’.

Trial design

Suboptimal PRO-specific trial design was cited by a large number (n = 22, 56%) of publications as a major barrier to realising PRO trial impact [40,41,42,43, 45,46,47, 49, 51, 52, 55, 62,63,64, 70, 72, 73, 76, 78, 81,82,83]. Particular areas of concern were selection of inappropriate or invalid PRO measures (n = 10, 52%). Lack of development of PRO cross-cultural items (n = 2, 9%). Broader methodological issues leading to potential bias and which may hinder PRO data use include allocation concealment, randomisation, blinding of participants and personnel and blinding of outcomes assessment (n = 7, 18%).

Conduct and analysis

Authors also highlighted that the way the trial was conducted and type of analysis carried out could act as an impact barrier. Over a third of publications (n = 12, 31%) identified PRO-specific barriers associated with trial conduct and analysis [40, 41, 56, 57, 62, 63, 70, 72, 73, 75, 78, 83]. The most frequent barriers mentioned by authors were low PRO compliance rates (n = 10, 83%), lack of personnel training on administration of PRO instruments (n = 3, 25%), incomplete follow-up of HRQL assessment (n = 2, 16%), selection of inappropriate statistical methods to handle missing data (n = 2, 16%).

Reporting

Incomplete or suboptimal reporting of PRO trial data was cited by 23 (65%) publications as a barrier to research impact if PRO trial findings and generalisability is not clearly presented [7, 38,39,40,41,42,43, 45,46,47,48,49,50,51,52,53, 56, 57, 63, 64, 72, 82, 83]. The most common barriers to impact were failure to report: the rationale for the chosen PRO instrument (n = 10, 43%), mode of administration (n = 10, 43%).

Use of PRO data in practice

Adoption of PRO trial findings into clinical practice was identified as somewhat problematic by 17 (43%) of the publications [39,40,41, 43, 45, 46, 52, 54,55,56, 61, 63, 64, 75, 78, 81, 82]. Key issues included lack of training/practice for clinicians on interpreting PRO data (n = 11, 64%) and lack of familiarity with PRO measures (n = 7, 41%).

Facilitators to impact

The review of the included articles identified a number of suggested facilitators purported to enhance the probability of realising PRO specific impact. Two (5%) authors suggested strict adherence to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) initiative to improve the completeness of trial protocols and reduce risk of bias [51, 62]. Eight (18%) authors proposed adherence to the Consolidated Standards of Reporting Trials (CONSORT) PRO Extension statement [7, 51,52,53, 56, 62, 64, 83] and two (5%) authors to the CONSORT statement [7, 51], in order to enhance transparency and complete reporting of PRO clinical trials. A detailed summary of the barriers and facilitators highlighted by the included publication are presented in Table 2, which includes additional resources identified by communication with methodological PRO experts (MC/DK).

Table 2 Barriers and facilitators to maximising PRO trial data
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REF 2014 impact case studies

Examples of clinical trial PRO impact were explored using REF2014 case studies. These identified a range of impact metrics.

Included studies

The search strategy yielded 209 REF 2014 impact case studies (PRISMA Flow Diagram, Additional file 3). Case studies were excluded if they did not include a clinical trial or the clinical trials did not incorporate a PRO element, meaning 69 relevant case studies were subsequently included in the analysis.

PRO clinical trials characteristics

The characteristics of the PRO clinical trials included across the eligible REF 2014 case studies are detailed in Table 3.

Table 3 PRO clinical trials characteristics
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Full details of the included case studies are available in Additional file 4. The assessment of the PRO trial metrics was considered using the ‘pathways to research impact’ framework [10]. Following this, two new additional impact metrics were identified, cost-effectiveness and drug/device approval. The summary of the PRO impact metrics is depicted in Fig. 2.

Fig. 2
figure 2

PRO trial impact metrics. *Additional PRO impact metrics identified. **There was not direct mention of this impact metric within the REF 2014 case studies; however, ‘drug approval’ could embrace the concept of patents granted/licenses awarded and brought to the market. Impact metrics were drew upon the ‘pathways to research impact’ framework [6]

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Real-world evidence of PRO impact

Assessment of the 69 eligible case studies determined that (n = 12, 17%) appeared to lead to direct demonstrable PRO impact, (n = 12, 17%) showed evidence of indirect PRO impact and (n = 45, 66%) provided no evidence of PRO impact (Fig. 2). Trials that included PROs as primary outcome (50%) reported a larger number of trials leading to direct impact than those trials that had PROs as secondary outcome (83%).

Direct PRO impact

The most common types of direct PRO impact presented across the case studies included: number of publications (n = 12, 17%), citation rates (n = 12, 17%), changes to international guidelines (n = 5, 7%), contribution to national guidelines (n = 4, 6%), contribution to evidence of cost-effectiveness (n = 3, 4%) and informing drug approval (n = 2, 3%). In addition, several case studies demonstrated more than one type of impact.

Indirect PRO impact

The most common types of indirect PRO impact included: number of publications (n = 12, 17%), citation rates (n = 12, 17%), changes to national guidelines (n = 10, 14%), contribution to international guidelines (n = 9, 13%) and national practice (n = 9, 13%) and contribution to evidence presented in conferences, seminars and workshops (n = 5, 7%).

Absence of evidence around PRO impact

The assessment of the included case studies demonstrated that the impact of PRO trial data is not usually captured in the long-term, specifically under the impact categories health and health system impacts, health related and social impact and economic impact.

Discussion

This manuscript is the first to present a systematic review aimed at identifying the potential types of PRO trial impact alongside real-world evidence of impact. It will allow researchers, clinicians, funders and policy-makers to consider pathways to research impact before conducting PRO trial research and to identify metrics to assess impact prospectively. In the same way, it will allow PRO stakeholders to consider facilitators at the design, conduct, analysis and reporting stages whilst avoiding recurrent barriers to generating PRO-specific impact and minimising research waste. High quality clinical trials involving PROs may lead to benefits for patients and society.

Nine types of potential PRO trial impact were identified (Fig. 1): informing clinical practice, informing clinical guidelines, informing health policy, supporting drug approval, supporting pricing and supporting reimbursement decisions, informing clinical and shared decision-making and informing consent for treatment. Only four impact metrics were proposed to measure the impact of PRO data, number of pharmaceutical claims and promotional labelling claims and inform drug/device approval and cost-effectiveness. Further research to formalise PRO-specific impact metrics is required.

Authors suggested that potential barriers to the use of PRO trial findings to inform healthcare decision-making and patient care included poor quality trial design, conduct, analysis, reporting and uptake in practice [55]. Several of the barriers comprised within ‘uptake of PRO trial results in practice’ (Table 2) are not unique to PRO clinical trials. These challenges are also encountered in the implementation of PRO data collected in routine clinical practice to inform patient care or for audit/benchmarking purposes. For instance, ‘high levels of missing data’ ‘overburden of staff, clinicians, participants and resources’, ‘lack of training/guidance for clinicians on interpreting PRO data’ are challenges commonly faced in routine practice [84, 85]. Furthermore, it is important to note that many of these challenges are not unique to PRO data/trials. Greater efforts are required to improve outcome selection, collection and reporting in both in trials and routine care [86, 87].

Suboptimal reporting of PRO trial data was the most discussed barrier (65%), which might hinder the maximisation of PRO trial findings. Therefore, addressing poor and incomplete reporting is essential, as it is unethical to waste research funding, resources and patients’ efforts and time invested during the collection PRO trial data [5, 6]. In recent years, a number of methodological guidelines have been developed to address the different barriers highlighted by this systematic review. These include: the SPIRIT-PRO Extension to improve the completeness of trial protocols [3]; The ongoing work of the SISAQOL Consortium to standardise the analysis and interpretation of PRO and quality of life from oncology clinical trials [88]; CONSORT-PRO Extension to facilitate optimal reporting guidance of trials that include PROs as primary or secondary outcome [46] and; the work carried out by Snyder et al. (2017) to present PRO trial findings [89]. The adoption of these guidelines has the potential to improve the design, conduct, analysis and report of PRO trials thus ensuring that high-quality data that may benefit patients and society are obtained from trials. The uptake of these guidelines is currently being promoted through PROTEUS (Patient-Reported Outcomes Tools: Engaging Users & Stakeholders) Consortium, which is funded by the US Patient Centred Outcomes Research Institute (PCORI) [90].

The literature suggests that adherence to guidelines should be endorsed/mandated by journals/editors in order to ensure high quality PRO data through the trial design, implementation, analysis and reporting stages. In addition, the FDA [2] and EMA [91] provide guidance to sponsors on reporting of PRO instrument development, measurement properties, implementation, analysis, and interpretation used to support drug approval and pharmaceutical labelling claims in the United States and Europe, respectively. Additional facilitators identified to maximise the realisation of impact in practice were reporting of PRO results adequately within the main trial publication, whilst considering journals word restrictions [43, 52, 53, 56, 64] and clinicians receiving training/guidance on interpretation of PRO data [41, 43, 52, 63]. Thus, it is essential that funders, ethics committees, journal editors and trial researchers proactively work together to ensure that PRO studies follow optimal design, conduct and analysis and reporting.

Although the systematic review publications may not have included information on PRO trial data impact, we explored whether evidence of impact could be identified from REF 2014 impact case studies as by their nature, they present an opportunity for researchers to highlight the impacts of their research. Sixty-nine REF 2014 case studies included a trial where PRO data were collected. Of these, 24 (34%) presented evidence of PRO trial impact that was classified as direct or indirect impact. Direct attribution of impact to PRO trial data was possible in 12 trials, most commonly informing national and international clinical guidelines. A number of potential impact categories are currently unrealised or under reported. This could be attributed to the fact that some of the PRO trials associated to the case studies have been published in the last years, which limits demonstration of PRO trial impact in the mid and long-term [10]. Furthermore, it was often difficult to unpick the exact contribution of PRO data to this impact as they were commonly combined with ‘clinical’ outcome data.

The REF 2014 case study ‘Heart failure: Improving the quality of life and survival of heart failure patients through Cardiac Resynchronisation Therapy’, submitted independently by the University of Birmingham [92] and Hull [93] is described below (Table 4) to illustrate the different facilitators that might help translating PRO findings into clinical practice. This example was chosen, as it is one of the case studies that have led to most varied impact and will provide researchers a useful guide about how to maximise PRO trial data and reduce research waste (Fig. 3).

Table 4 Practical guide for researchers
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Fig. 3
figure 3

CARE-HF Trial Pathways to PRO Trial Impact. Logos reproduced with permission of ESC and ACC

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However, reported barriers and facilitators in the literature focused predominantly on the PRO clinical trial design, conduct and analysis stages. There was a dearth of information on how to address barriers to generating PRO trial impact in practice. Additionally, identified impact was mainly focused on primary research (e.g. publications, citations and conference). There was little attention on policy-making, health & health systems, health related & societal and economic impact, which is generally realised in the mid and long term. Thus, further research in this area is required to identify facilitators to maximise PRO trial impact in the longer term. This will be achieved through interviews with international stakeholders in order to explore in-depth perceived barriers and facilitators to effective dissemination and impact on healthcare decisions and patient care. Work will be conducted to refine the ‘pathways to research impact’ framework in the context of PRO trial impact. In addition, it is important to mention that it is well established that certain impact categories (e.g. primary research impact via publications) are easier to measure than others (e.g. societal impact), which can limit the number of available impact metrics to measure the impact of PRO trial data.

Limitations

This systematic review summarised the different types of impact thought to be associated with PRO trial findings and proposes metrics to measure impact in practice. The main limitation was that due to poor indexing, over half of the included publications were identified through hand-searching of references lists and citation searches methods rather than databases searching. Therefore, some relevant publications might not be included in this article if they failed to mention a type of impact in the title/abstract. However, we made efforts to identify all the relevant publications. The search strategy adopted did not include the search term ‘self-rated health’, which could have led to the exclusion of relevant articles. Nonetheless, our search strategy was informed by the Oxford PROM Group Construct & Instrument Type Filter [94], which was modified according to the objectives of this systematic review. Although there were no language restrictions, we did not systematically search non-English databases. In addition, a formal quality appraisal was not undertaken to assess the quality of the studies included. We acknowledge that a significant amount of the evidence we found was based on expert opinion, which does not rank highly in the evidence hierarchy. Furthermore, a small number of the included studies were discussed by different authors, which may have influenced the frequency counts. However, this does not affect the conclusions of this systematic review.

The ‘pathways to research impact’ framework was used to measure the impact of PRO trial data. This framework was selected as it synthetises all the existing types of healthcare research impact and metrics (Fig. 2). However, not all the types of impact outlined by the framework are relevant to PRO trial data (e.g. human rights and United Nation Millennium Development Goals). The REF is an expert review process solely focused on the UK HEIs, which may limit the generalisability of the impact of the PRO data, although 30% of the trials were categorised as international trials. In some instances, it was not possible to confirm the impact described by the REF 2014 impact case studies, as there was no access to some sources provided. It is important to consider that the case studies had word count restrictions, which could have led to under reporting of impact. In addition, the majority of the articles included in the first section of the systematic review focused on oncology. Therefore, the findings presented in this study can only be generalised to oncology PRO clinical trials.

Conclusion

This review provides a summary of the different types of potential PRO impact identified in the literature, supported by real-world examples. The impact of PRO clinical trials can be attributed to PRO results and measured through different impact metrics. It is essential that researchers and authors design, conduct and analyse and report high quality PRO trial results and; proactively tackle barriers to PRO impact in order to maximise the impact of PRO clinical trials in the short, mid and long term to fully realise benefits for society. Adherence to guidance and multi-stakeholder collaboration is essential to maximise the utilisation of PRO trial data, while minimising research waste and maximising future patient care.