Setting International Standards in
Analysing Patient-Reported Outcomes
and Quality of Life Endpoints
Publications
Single-arm studies involving patient-reported outcome data in oncology: a literature review on current practice
Liu L, Choi J, Musoro JZ, Sauerbrei W, et al. The Lancet Oncology. 2023
Patient-reported outcomes (PROs) are increasingly used in single-arm cancer studies. We reviewed 60 papers published between 2018 and 2021 of single-arm studies of cancer treatment with PRO data for current practice on design, analysis, reporting, and interpretation. We further examined the studies’ handling of potential bias and how they informed decision making. Most studies (58; 97%) analysed PROs without stating a predefined research hypothesis. 13 (22%) of the 60 studies used a PRO as a primary or co-primary endpoint. Definitions of PRO objectives, study population, endpoints, and missing data strategies varied widely. 23 studies (38%) compared the PRO data with external information, most often by using a clinically important difference value; one study used a historical control group. Appropriateness of methods to handle missing data and intercurrent events (including death) were seldom discussed. Most studies (51; 85%) concluded that PRO results supported treatment. Conducting and reporting of PROs in cancer single-arm studies need standards and a critical discussion of statistical methods and possible biases. These findings will guide the Setting International Standards in Analysing Patient-Reported Outcomes and Quality of Life Data in Cancer Clinical Trials–Innovative Medicines Initiative (SISAQOL-IMI) in developing recommendations for the use of PRO-measures in single-arm studies.
Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI): stakeholder views, objectives, and procedures
Pe M, Alanya A, Falk RS, Amdal CD et al. The Lancet Oncology. 2023
Patient-reported outcomes (PROs), such as symptoms, functioning, and other health-related quality-of-life concepts are gaining a more prominent role in the benefit–risk assessment of cancer therapies. However, varying ways of analysing, presenting, and interpreting PRO data could lead to erroneous and inconsistent decisions on the part of stakeholders, adversely affecting patient care and outcomes. The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI) Consortium builds on the existing SISAQOL work to establish recommendations on design, analysis, presentation, and interpretation for PRO data in cancer clinical trials, with an expanded set of topics, including more in-depth recommendations for randomised controlled trials and single-arm studies, and for defining clinically meaningful change. This Policy Review presents international stakeholder views on the need for SISAQOL-IMI, the agreed on and prioritised set of PRO objectives, and a roadmap to ensure that international consensus recommendations are achieved.
An Emerging Trend in Oncology: Global Initiatives Incorporating Patient-Reported Outcomes.
PE M. European Society For Medical Oncology, Madrid, Spain, October 2023.
The use of PRO data in cancer randomised controlled trials (RCTs): Literature reviews on current practices and guidelines.
Cocks K, Catalan C, Machingura A, Coens C, et al. ISOQOL, Calgary, Canada, October 2023.
Background: Complementary to classical efficacy and safety endpoints, there is a growing use of patient reported endpoints for cancer drug development. Therefore, patients’ perception of their disease, treatment, and other health-related quality of life issues has become an integral part of clinical trial research objectives. These perceptions are captured through patient-reported outcomes (PRO) and play an essential role in cancer clinical trials for the evaluation of cancer treatments. This scoping review aimed to evaluate current practices, existing guidelines, and methodological recommendations on the use of PRO data in cancer treatment RCTs. Results of this review will inform the development of the SISAQOL-IMI recommendations and hence standardized guidelines.
Methods : A literature search on current practices and guidelines was conducted on PubMed, clinicaltrials.gov and EMA, according to PRISMA principles. Additionally, documents and guidelines used by different stakeholders (i.e., FDA, EMA, ICH and HTA) were considered in the review process. Eligible sources were published protocols, guidelines, recommendations, and systematic reviews that are relevant to the use of PRO endpoints in cancer randomized trials. After the screening process, 29 protocols were identified, 14 articles were selected from European public assessment reports from EMA, and 6 systematic reviews on current PRO practices. In addition, 12 methodological guidelines and 12 stakeholder’s guidelines were fully reviewed.
Results: The review revealed that there is a lack of precision on PRO objectives, such as pre-specifying the PRO domains and key time point of analysis. Results also showed that specific intercurrent events relevant to PROs like handling of death or treatment discontinuation are often ignored. We also observed a lack of consistency between trials with respect to frequency of assessments, follow-up times, and data handling after treatment discontinuation. Furthermore, current guidelines and recommendations fail to cover these aspects.
Conclusion: There is a need to increase transparency of underlying PRO research questions and reporting of relevant intercurrent events like death and treatment discontinuation. The work of SISAQOL-IMI on the estimand framework will clarify how PRO endpoints should be determined. Moreover, analytical approaches should be sufficiently detailed to fully understand the interpretation of the reported PRO results, which would in turn, facilitate comparative insights on the oncology-patients experience.
An Emerging Trend in Oncology: Global Initiatives Incorporating Patient-Reported Outcomes.
Mulkey F, Chen T, Pe M, Cappelleri J, Bhatnagar V, Fiero M. ASA Biopharmaceutical Section Regulatory-Industry Statistics Workshop, Rockville, USA, September 2023.
In this session, regulatory, industry and academic representatives will present an update on current local and global efforts on incorporating and improving interpretation of PROs throughout different stages of oncologic drug development. Regulatory representatives from the FDA will highlight how several initiatives through OCE have provided a framework for more effective collection and use of PROs in oncology trials. Pertinent case examples with a focus on estimands and the clinical perspective for interpretation of PROs will provide context for the panel discussion. FDA leaders will discuss issues with the current paradigm of dose selection as highlighted in Project Optimus and focus on how PROs can be used to characterize safety and tolerability, thereby guiding dose optimization. An overview of Project Patient Voice will demonstrate how publicly available patient-reported symptom data can help patients and healthcare providers understand the patient’s experience in a later phase trial. An overview of the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials (SISAQOL) consortium which includes global representatives from industry, academia, and international regulatory agencies, will also be highlighted.
Generating recommendations for design, analysis and interpretation of patient-reported outcomes for cancer clinical trials: Progress from SISAQOL-IMI.
Cocks K, PE M, Coens C, Schlichting M, et al. Royal Statistical Society, Harrogate, USA, September 2023.
Patient-reported outcomes (PROs) are increasingly used in cancer clinical trials to provide information on treatment risks, benefits and tolerability. However, there is no consensus on optimal methods for PRO analysis, hindering the interpretation of results, comparability of results across different trials and therefore restricting the utility of PRO data in product labelling, clinical guidelines and health policy.
SISAQOL-IMI (Setting International Standards in Analysing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials) is an international multidisciplinary consortium with funding from the Innovative Medicines Initiative. This four-year collaborative project was launched in 2021 and will develop a set of standards for the design, analysis, interpretation and presentation of patient-reported outcomes.
This presentation will give an overview of the project and its aims followed by an introduction to the four scientific work packages and the key statistical issues they are addressing. The scientific work packages cover analysis in randomised controlled trials (RCTs), single arm studies, graphical presentation and clinically meaningful difference.
The presentation will discuss some of the key challenges in achieving harmonisation and standardisation for statistical analysis of PROs; the analysis of PROs within the estimand framework (valid PRO objectives and handling of death and disease progression as intercurrent events), presentation of multi-dimensional, longitudinal PRO data and recommendations for improving the interpretation of PRO analyses results.
As the SISAQOL-IMI project is still in progress the presentation aims to provide an opportunity for RSS members to participate and feed into the ongoing work of the consortium.
Developing recommendations to handle patient reported outcome data in oncology cancer trials: sisaqol-imi.
Le Cessie S, Goetghebeur E, Thomassen D. International Society for Clinical Biostatisticians, Milan, Italy, August 2023.
This talk is on behalf of work package 3 of the SISAQOL-IMI consortium. SISAQOL-IMI is an international project, led by the European Organisation for Research and Treatment of Cancer (EORTC) and Boehringer Ingelheim. The aim of this four year project is to establish international standards in the analysis of patient reported outcomes (PRO) and health-related quality of life data in cancer clinical trials. This is done by seeking consensus internationally and across stakeholders (industry, academics, patients, trial organizations, regulators, etc). STRATOS is involved in this large project, in particular in the work package on single arm trials and other non randomized studies. We are now halfway through this project and currently a set of suggested recommendation for PROs in single arm oncology studies is piloted on case studies. arm oncology studies is piloted on case studies. The recommendations consider the aims of PROs in single arm studies, formulation of research questions in the context of the ICH E9(R1) estimand framework (1), choosing appropriate outcome measures, addressing the absence of a randomised control group, and handling intercurrent events and missing data. In this talk we will give an update on the current status of our work and discuss questions and challenges in the design and analysis of single arm PRO studies.
Imputation of longitudinal patient reported outcomes in the presence of death and other intercurrent events.
Thomassen D, Roychoudhury S, Delphin CA, Liu L, et al. International Society for Clinical Biostatisticians, Milan, Italy, August 2023.
Patient reported outcomes (PROs) such as health-related quality of life and symptom severity can correlate with the occurrence of intercurrent events (e.g., death, disease progression): for instance, a decrease in health-related quality of life may precede death. At the same time, intercurrent events may impede PRO measurement, leading to missing data. We encountered this in a single arm trial where health-related quality of life was repeatedly measured and where the mortality rate was high. Since PROs after death are not defined, our estimand was the mean PRO at each time point in those who were still alive, regardless of treatment discontinuation or disease progression[1]. Marginal means from a standard linear mixed model (LMM) were not appropriate here, as they are based on implicit imputation of missing PROs, ignoring the relation with intercurrent events and extrapolating PROs after death. Therefore, our aim was to derive methods to deal with missing PRO data before death, assuming missingness at random conditional on the longitudinal trajectory of the PRO; the individual timing of progression of disease (PD), treatment discontinuation (TD) and death. An important challenge was censoring: the times of PD and death were not observed for all patients. We imputed missing PROdata until death or censoring, after which we reweighted for censoring in the analysis. To this end, we formulated single and multiple imputation models: LMMs, multivariate normal models in MICE and a predictive mean matching-model in MICE[2]. The models conditioned on time-varying variables specifying the time to death, PD and TD; time-varying indicators of the event, and censoring indicators. We varied the coding of the time- to-event variables (linear, splines, a change of slope at event times) and the addition of interactions with the indicators in model specification. Imputation conditional on intercurrent events generally led to lower estimated mean health- related quality of life (while alive) over time compared to available data; particularly with increasing incidence of intercurrent events. Variations in the imputation models led to noteworthy differences in their estimates and standard errors. We demonstrate how the imputation models’ assumptions about the relation between the PRO and intercurrent events ct the resulting estimates. Abstract submitted on behalf of SISAQOL-IMI Work Package 3.
Imputation of longitudinal patient reported outcomes in the presence of death and other intercurrent events.
Goetghebeur E, Reynerds D, Thomassen D, Le Cessie S. International Society for Clinical Biostatisticians, Milan, Italy, August 2023.
The EU IMI_SISAQOL project https://www.imi.europa.eu/projects-results/project-factsheets/sisaqol-imi develops guidelines for evaluating the effect of novel treatments on PROMs in oncology populations. STRATOS helps develop statistical guidelines as a partner in this project. When mortality is high, we consider `time to death’ in combination with `Quality of life (QOL)- while-alive’ as the bivariate real-world outcome. From a statistical perspective, comparing treatments in terms of this outcome is wrought with major challenges. First, death is a terminal event for any patient-reported outcome, and especially for quality of life. While obvious, implications for statistical analysis and interpretation are often ignored. This happens for instance, when parameters in mixed models for QOL measures taken repeatedly over time get a direct interpretation which implicitly imputes QOL-after-death. Averaging derived predictions among the living at a given time t is then warranted but GEE models target the real world estimand more directly. Second, in single arm studies as in RCTs, the question arises `in which populations to compare QOL(t*) (at a chosen time t*) with and without treatment’. To this end, we identify a control group with overlapping entry and exclusion criteria where a common `core set’ of confounder variables is measured at baseline t0, and the positivity assumption holds. The combined propensity of treatment at t0 and propensity of censoring avoidance at t* enable adjustment for measured confounders and explainable censoring, respectively. An extra between study variation on the standardized QOL(t*), then yields a `real world’ Confidence Interval for the population Average Treatment Effect (among the Treated), The final challenge arises when at disease progression or change of treatment one stops measuring QOL. Besides death as an intercurrent event, and administrative censoring there are missing QOL data, with missingness likely dependent on time to subsequent death. We argue in favour of a well understood real world analysis and present challenges and solutions in the setting of a single arm study seeking an external control group. We illustrate how the three challenges can be handled jointly in our case study.
What do we know about visualisation of group-level PRO data from cancer clinical trials for healthcare professionals and other stakeholders? Results from a systematic literature review.
Wintner L, Gross F, Peacock R, Boele F, et al. ISOQOL, Prague, Czech Republic, October 2022.
Aims: As part of the SISAQOL-IMI project, currently developing standards for the use, analysis and interpretation of patient-reported outcome (PRO) data in cancer clinical trials, work package 4 (WP4) performed systematic literature searches to gather existing knowledge on how PRO trial data should be visually presented to different stakeholder groups. This abstract reports findings for healthcare professionals (HCPs) and other stakeholders (e.g. researchers, policy makers, regulatory authorities).
Methods: A two-step approach was applied for searching Web of Science, EBSCOhost and the Cochrane Library: Search 1 identified trials investigating graphical presentation formats of PRO data in oncology and search 2 identified more broadly visualisation advice for PRO data irrespective of the medical field. Two independent reviewers screened each reference (title/abstract, full text; FG, RP, and/or LW) and one researcher (FG or RP) performed data extraction (subjected to quality control; LW). Disagreements were resolved through discussion. According to the aim of WP4, only references with group-level PRO data visualisations were included in the qualitative synthesis.
Results: Fig. 1 presents the reference flow. The selection process resulted in 32 references, of which 19 provided information on the visualisation of group-level PRO data. Far less information could be extracted for other stakeholders than for HCPs. For both stakeholder groups, there is no clear preference of a visualisation type, though bar charts are valued for side-by-side comparisons. Pie charts are well understood and positively rated for proportions changed data. Regarding statistical parameters, both stakeholder groups ask for raw numbers or percentages (especially in pie charts), an asterisk marking statistical significance and sample size numbers below the x-axis. Preferences for including confidence intervals or information on clinical significance are inconsistent, although it is usually noted that this information could facilitate interpretation if properly understood.
Conclusion: Existing literature provides only few clear recommendations on the graphical presentation of group-level PRO data for HCPs/other stakeholders. The further work of SISAQOL-IMI WP4 will help to advance the knowledge on graphical reporting of PRO trial data for these stakeholders.
Disclaimer: The content of this abstract MUST NOT be taken as recommendations of the SISAQOLIMI consortium. Findings for patients are reported in a separate abstract.
Developing international standards in the analysis of patient reported outcomes in cancer clinical trials: methodological issues and STRATOS engagement in the European IMI-SISAQOL project.
Le Cessie S, Goetghebeur E, Liu L, Thomassen D. International Society for Clinical Biostatisticians, Newcastle, England, August 2022.
What do we know about visualisation of group-level PRO data from cancer clinical trials for patients? Results from a systematic literature review.
Gross F, Wintner L, Peacock R, Boele F, et al. ISOQOL, Prague, Czech Republic, October 2022.
Aims: As part of the SISAQOL-IMI project, currently developing standards for the use, analysis and interpretation of patient-reported outcome (PRO) data in cancer clinical trials, work package 4 (WP4) performed systematic literature searches to gather existing knowledge on how PRO trial data should be visually presented to different stakeholder groups. This abstract reports findings for patients.
Methods: A two-step approach was applied for searching Web of Science, EBSCOhost and the Cochrane Library: Search 1 identified trials investigating graphical presentation formats of PRO data in oncology and search 2 identified more broadly visualisation advice for PRO data irrespective of the medical field. Two independent reviewers screened each reference (title/abstract, full text; FG, RP, and/or LW) and one researcher (FG or RP) performed data extraction (subjected to quality control; LW). Disagreements were resolved through discussion. According to the aim of WP4, only references with group-level PRO data visualisations were included in the qualitative synthesis.
Results: Fig. 1 presents the reference flow. The selection process resulted in 32 references, of which 19 provided information on the visualisation of group-level PRO data. Literature does not indicate a clear preference of any type of visualisation for patients. Line graphs, pie charts and bar charts are considered reasonable options and longitudinal data presentation is favoured. Statistical details tend to be found confusing by patients, though numerical reporting of numbers or percentages and highlighting of statistically significant results is appreciated. Labels indicating the direction of better and worse scores are considered helpful for interpretation. Patients value textual explanations that help them understand the graph. Literature generally suggests to keep visualisations simple for patients, but educational differences can affect both preferences and understanding.
Conclusion: Although literature provides some specific recommendations on the graphical presentation of PRO trial data to patients, further research is needed to address their particular needs, which might vary even within this stakeholder group. The work of SISAQOL-IMI WP4 will help to advance knowledge in this regard.
Disclaimer: The content of this abstract MUST NOT be taken as recommendations of the SISAQOLIMI consortium. Findings for health care professionals and other stakeholders are reported in a separate abstract.
SISAQOL | IMI: Evaluating treatment effects on quality of life in oncology.
Goetghebeur E, Liu L, Thomassen D, Le Cessie S.
SISAQOL | IMI: Evaluating treatment effects on quality of life in oncology.
ten Seldam S, Morgan K , Joyner K, Papadopoulos E, et al. WECAN academy, Frankfurt, Germany, July 2023
Conference ¦ Poster PDF
Patient reported outcomes in Oncology Studies: Intercurrent Events.
ten Seldam S, Papadopoulos E, Pe M, Alanya A. WECAN academy, Frankfurt, Germany, July 2023
The session will focus on issues researchers face with patient-reported outcomes (PROs) in cancer clinical trials. You will learn about what is needed to put PROs into practice in oncology studies (design, analysis, reporting). You will also learn what intercurrent events are, why it is important to understand them and what patient advocates should look for when reviewing clinical trial protocols and study results. Ultimately, this session will provide you with the knowledge and tools to provide more critical feedback when reviewing protocols.
Many patients and advocates have been involved with reviewing clinical trial protocols, and the value of this is being recognised more broadly by industry, researchers, and other stakeholders. As the advocacy community continues to push for earlier involvement, you may be involved in the design of clinical trials during their initial development. Therefore, it is important to understand topics like intercurrent events, how differences in clinical trial design can result in different outcomes and how to provide constructive feedback. This session will focus in particular on issues for PROs. Ensuring PROs are evaluated and reported in a consistent manner across cancer clinical trials and in line with the research questions means that the impact that treatment has on a patient’s quality of life will be better captured and communicated to stakeholders to support fair and informed decision making.
Conference ¦ Educational workshop summary
Year 1 consensus meeting executive summary
PDF ¦ Plain Version
Year 2 consensus meeting executive summary
PDF ¦ Plain Version
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Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium. International standards for the analysis of quality-of-life and patient-reported outcome endpoints in cancer randomised controlled trials: recommendations of the SISAQOL Consortium.
Coens C, Pe M, Dueck AC, Sloan J, Basch E et al. The Lancet Oncology. 2020
Patient-reported outcomes (PROs), such as symptoms, function, and other health-related quality-of-life aspects, are increasingly evaluated in cancer randomised controlled trials (RCTs) to provide information about treatment risks, benefits, and tolerability. However, expert opinion and critical review of the literature showed no consensus on optimal methods of PRO analysis in cancer RCTs, hindering interpretation of results. The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium was formed to establish PRO analysis recommendations. Four issues were prioritised: developing a taxonomy of research objectives that can be matched with appropriate statistical methods, identifying appropriate statistical methods for PRO analysis, standardising statistical terminology related to missing data, and determining appropriate ways to manage missing data. This Policy Review presents recommendations for PRO analysis developed through critical literature reviews and a structured collaborative process with diverse international stakeholders, which provides a foundation for endorsement; ongoing developments of these recommendations are also discussed.
Statistical analysis of patient-reported outcome data in randomized controlled trials of locally advanced and metastatic breast cancer: a systematic review.
Pe M, Dorme L, Coens C, Basch E et al. The Lancet Oncology. 2018
Although patient-reported outcomes (PROs), such as health-related quality of life, are important endpoints in randomised controlled trials (RCTs), there is little consensus about the analysis, interpretation, and reporting of these data. We did a systematic review to assess the variability, quality, and standards of PRO data analyses in advanced breast cancer RCTs. We searched PubMed for English language articles published in peer-reviewed journals between Jan 1, 2001, and Oct 30, 2017. Eligible articles were those that reported PRO results from RCTs of adult patients with advanced breast cancer receiving anti-cancer treatments with reported sample sizes of at least 50 patients-66 RCTs met the selection criteria. Only eight (12%) RCTs reported a specific PRO research hypothesis. Heterogeneity in the statistical methods used to assess PRO data was observed, with a mixture of longitudinal and cross-sectional techniques. Not all articles addressed the problem of multiple testing. Fewer than half of RCTs (28 [42%]) reported the clinical significance of their findings. 48 (73%) did not report how missing data were handled. Our systematic review shows a need to improve standards in the analysis, interpretation, and reporting of PRO data in cancer RCTs. Lack of standardisation makes it difficult to draw robust conclusions and compare findings across trials. The Setting International Standards in the Analyzing Patient-Reported Outcomes and Quality of Life Data Consortium was set up to address this need and develop recommendations on the analysis of PRO data in RCTs.
Moving forward towards standardizing analysis of quality of life data in randomized cancer clinical trials.
Bottomley A, Pe M, Sloan J, Basch E et al. Clinical Trials. 2018
Background: There is currently a lack of consensus on how health-related quality of life and other patient-reported outcome measures in cancer randomized clinical trials are analyzed and interpreted. This makes it difficult to compare results across randomized controlled trials (RCTs) synthesize scientific research, and use that evidence to inform product labeling, clinical guidelines, and health policy. The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data for Cancer Clinical Trials (SISAQOL) Consortium aims to develop guidelines and recommendations to standardize analyses of patient-reported outcome data in cancer RCTs.
Methods and Results: Members from the SISAQOL Consortium met in January 2017 to discuss relevant issues. Data from systematic reviews of the current state of published research in patient-reported outcomes in cancer RCTs indicated a lack of clear reporting of research hypothesis and analytic strategies, and inconsistency in definitions of terms, including “missing data,”“health-related quality of life,” and “patient-reported outcome.” Based on the meeting proceedings, the Consortium will focus on three key priorities in the coming year: developing a taxonomy of research objectives, identifying appropriate statistical methods to analyze patient-reported outcome data, and determining best practices to evaluate and deal with missing data.
Conclusion: The quality of the Consortium guidelines and recommendations are informed and enhanced by the broad Consortium membership which includes regulators, patients, clinicians, and academics.
Analysing data from patient-reported outcome and quality of life endpoints for cancer clinical trials: a start in setting international standards.
Bottomley A, Pe M, Sloan J, Basch E et al. The Lancet Oncology. 2018
Measures of health-related quality of life (HRQOL) and other patient-reported outcomes generate important data in cancer randomised trials to assist in assessing the risks and benefits of cancer therapies and fostering patient-centred cancer care. However, the various ways these measures are analysed and interpreted make it difficult to compare results across trials, and hinders the application of research findings to inform publications, product labelling, clinical guidelines, and health policy. To address these problems, the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) initiative has been established. This consortium, directed by the European Organisation for Research and Treatment of Cancer (EORTC), was convened to provide recommendations on how to standardise the analysis of HRQOL and other patient-reported outcomes data in cancer randomised trials. This Personal View discusses the reasons why this project was initiated, the rationale for the planned work, and the expected benefits to cancer research, patient and provider decision making, care delivery, and policy making.
A new international initiative to Harmonize Analysis of Cancer Patient-Reported Outcomes.
Gotay C, Pe M, Corneel C, Basch E et al. The 21st World Congress of Psycho-Oncology, Banff, Canada, September 2019.
Background/rationale or Objectives/purpose: Patient-reported outcomes (PROs) are increasingly identified as important data to inform risks and benefits of cancer treatments. However, current inconsistency in defining, analyzing and interpreting PRO endpoints impedes their use and comparison of results across RCTs. Therefore, an international collaboration was formed: the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) Consortium. Methodology or Methods: SISAQOL activities include face-to-face meetings, conference calls, email communications, surveys using a modified Delphi process, and formation of subgroups to focus on specific issues. Impact on practice or Results: SISAQOL started with an initial group of experts who recommended enlarging the membership to ensure that its international and multidisciplinary scope included leading PRO researchers and statisticians, experts from international oncologic and academic societies, advisory and regulatory bodies, pharmaceutical industry, cancer institutes, and patient advocacy organizations. The group identified the lack of common definitions for many concepts and techniques used in PRO analysis. Subgroups worked to define PRO terms and research objectives and matched them with appropriate statistical methods, and explored approaches to analyzing missing data. Development of consensus recommendations for PRO analysis in cancer RCTs is in progress. Discussion or Conclusions: The SISAQOL Consortium uses a participatory group process that builds on the needs, knowledge and expertise of diverse stakeholders with the goal of developing robust standards for PRO analysis in cancer RCTs. Including PROs in RCTs costs time, money and/or effort from all stakeholders, including patients. Harmonizing the analysis of these data will enhance their interpretability and impact. This publication reflects solely the views of the individual authors.
Towards standardization of patient-reported (PRO) data analysis in cancer randomized controlled trials: the SISAQOL initiative.
Coens C, Pe M, Basch E, Calvert M et al. PSI Annual conference, QEII Centre, London, UK, June 2019.
Developing International Standards and Recommendations for the Analysis of Patient-Reported Outcomes and Quality of Life Data.
Dorme L, Pe M, Coens C, Basch E et al. PROMS Annual Research Conference 2019, Leeds Beckett University, Leeds, UK, June 2019.
Setting standards in patient-reported outcomes analysis for cancer randomized controlled trials – a SISAQOL initiative update.
Coens C, Pe M, Basch E, Calvert M et al. 40th Annual Conference of the International Society for Clinical Biostatisticians, O&N Gasthuisberg, Leuven, BE, July 2019.
Current State of Statistical Analysis of Patient Reported Outcomes Data in Cancer Randomized Controlled Trials on Locally Advanced and Metastatic Breast Cancer – A Systematic Review.
Pe M, Dorme L, Coens C, Hamel JF et al. PROMS Research Conference, University of Birmingham, Birmingham, UK, June 2018.
Current State of Statistical Analysis of Patient Reported Outcomes Data in Cancer Randomized Controlled Trials on Locally Advanced and Metastatic Breast Cancer – A Systematic Review.
Pe M, Dorme L, Coens C, Hamel JF et al. PROMS Research Conference, University of Birmingham, Birmingham, UK, June 2018.
Setting Standards for Analysis of Patient Reported Outcomes and Quality of Life Data for International Cancer Clinical Trials (SISAQOL consortium): Progress update.
Bottomley A, Pe M, Dorme L, Hamel JF et al. 25th Annual Conference of the International Society for Quality of Life Research, Dublin, Ireland October 2018.
Improving standards of patient reported outcomes analysis: developing a consensus taxonomy of key research objectives – a SISAQOL initiative.
Pe M, Dorme L, Coens C, Hamel JF et al. 25th Annual Conference of the International Society for Quality of Life Research, Dublin, Ireland, October 2018.
How Much Missing Data is Too Much? Monte Carlo Simulations to Develop SISAQOL Guidelines for Missing Data Handling.
Mazza G, Pe M, Dorme L, Coens C et al. 25th Annual Conference of the International Society for Quality of Life Research, Dublin, Ireland October 2018.
Setting Standards for Analysis of Quality of Life Data for International Cancer Clinical Trials (SISAQOL Consortium).
Bottomley A, Pe M, Sloan J, Basch E et al. ECCO2017: European Cancer Congress, Amsterdam, The Netherlands, January 2017.
Setting Standards for Analysis of Quality of Life Data for International Cancer Clinical Trials (SISAQOL Consortium).
Coens C , Pe M, Sloan J, Basch E et al. 23rd Annual Conference of the International Society for Quality of Life Research, Copenhagen, Denmark, October 2016.
A Systematic Review on the Choice and Implementation of Statistical Methods in Health-Related Quality of Life Data Analyses in Locally Advanced and Metastatic Breast Cancer Randomized Controlled Trials (SISAQOL Consortium).
Pe M , Bottomley A, Bonnetain F, Campbell A et al. 23rd Annual Conference of the International Society for Quality of Life Research, Copenhagen, Denmark, October 2016.
The SISAQOL initiative: Establishing International Standards and Recommendations for the Analysis of Patient-Reported Outcomes and Quality of Life Data in Oncology Randomized Clinical Trials
Dorme L, Pe M, Coens C, Basch E et al. ISPOR Europe 2019, Copenhagen, Denmark, November 2019.
OBJECTIVES : Patient-reported outcome (PRO) data, such as symptoms and health-related quality of life, are increasingly being captured in cancer randomized clinical trials (RCTs) to provide valuable information on treatment risks, benefits and tolerability. Our literature review showed heterogeneity in analysis, interpretation and reporting of these data in various cancer fields, hindering comparability in results across trials. The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) Consortium was convened to set recommendations for PRO analysis in cancer RCTs.
METHODS : The Consortium comprises 40 international experts including PRO researchers and statisticians, representatives from regulatory bodies, academic societies, pharmaceutical industry, cancer institutes and patient organizations to work on four priorities: (a) specification of well-defined PRO research objectives, (b) recommendations for appropriate statistical PRO analysis methods, (c) standardization of statistical terminology and (d) development of guidelines for analyzing missing data. Recommendations were developed through literature review, surveys, meeting discussions and ratified through voting in a final meeting.
RESULTS : A taxonomy of research objectives was developed. Appropriate statistical methods, with the exception of summary measures, were proposed. Consensus was reached on the taxonomy of research objectives and statistical methods, along with a missing data definition and two rates to report missing data occurrence. While some statements concerning handling missing data or statistical analyses are still to be discussed, many statements were ratified for each of the priorities.
CONCLUSIONS : A robust first set of PRO analyses recommendations were established in a joint process with diverse international stakeholders. Addressing the needs and requirements of these stakeholders provides a strong foundation for widespread endorsement of these recommendations. Ultimately, we expect enhanced interpretability and better impact of PRO data in cancer RCTs from harmonization of current research practices.
The SISAQOL initiative: Establishing International Standards and Recommendations for the Analysis of Patient-Reported Outcomes and Quality of Life Data in Oncology Randomized Clinical Trials. ISPOR Europe 2019, Copenhagen, Denmark, November 2019.
Setting International Standards in Analysing patient-reported outcomes and quality of life endpoints data for cancer clinical trials – SISAQOL Consortium.
Bottomley A, Pe M, Sloan J, Basch E et al. ECCO2017: European Cancer Congress, Amsterdam, The Netherlands, January 2017.
Analysis of PRO data: SISAQOL recommendations and practical examples.
Presenter: Kim Cocks. PSI One day Scientific Meeting: The analysis and reporting of PROs in Clinical Trials, Roche, Welwyn Garden City, UK, July 2019.
International standards of Analysis – The SISAQOL initiative (SISAQOL Consortium).
Madeline Pe. 5th EORTC Quality of Life and Cancer Clinical Trials Conference, Brussels, Belgium, May 2019.
Efforts to Standardize PRO Analysis Methods.
Chair: Laura Lee Johnson. Presenters: Andrew Bottomley, Kathy Soltys, Amylou Dueck, Rajeshwari Sridhara. ASCO FDA Core Outcome Assessments in Cancer Clinical Trials (COA-CCT) Workshop, Silver Spring, USA, June 2018.
International standards of Analysis – The SISAQOL initiative (SISAQOL Consortium).
Presenter: Madeline Pe. Quality of Life and Cancer Clinical Trials Conference, Brussels, Belgium, April 2017.
The Challenge of Missing Data. What can we, as patient advocates, do to help? (Incorporating the EORTC’s SISAQOL Initiative).
Presenters: Jeff Sloan and Madeline Pe. The Third Biennial World Summit of Brain Tumour Patient Advocates, London, United Kingdom, October 2017.
Getting the maximum out of patient reported data in clinical trials: an update on the SISAQOL initiative.
Dorme L, Oliver K (on behalf of the SISAQOL Consortium). Brain Tumour Magazine: World Edition 2019, p: 26-28.
PROs and HRQOL: Are we talking about the same things? Challenges in interpreting PRO and HRQOL findings across trials.
Presenter: Madeline Pe. WECAN Academy 2019, Frankfurt, Germany, July 2019.
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