Quality of missing data reporting and handling in palliative care trials demonstrates that further development of the CONSORT statement is required: a systematic review

Hussain, Jamilla; Bland, Martin; Langan, Dean; Johnson, Miriam J.; Currow, David C.; White, Ian R.

doi:10.1016/j.jclinepi.2017.05.009

Cited by 39 publications

(40 citation statements)

References 43 publications

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“…Reasons for attrition vary and may be a result of trial design, patient population or the intervention, but patient withdrawal and loss to follow up are the most common causes [ 19 , 20 ]. Loss to follow up can be a passive form of withdrawal, where patients fail to complete follow up without formally ending their trial involvement.…”

Section: Discussionmentioning

confidence: 99%

Reducing attrition within clinical trials: The communication of retention and withdrawal within patient information leaflets

et al. 2018

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BackgroundThe recruitment and retention of patients are significant methodological challenges for trials. Whilst research has focussed on recruitment, the failure to retain recruited patients and collect outcome data can lead to additional problems and potentially biased results. Research to identify effective retention strategies has focussed on influencing patient behaviour through incentives, reminders and alleviating patient burden, but has not sought to improve patient understanding of the importance of retention. Our aim is to assess how withdrawal, retention and the value of outcome data collection is described within the Patient Information Leaflets (PIL) used during consent.MethodsFifty adult or parent PIL from a cohort of trials starting between 2009–2012 and funded by the NIHR Health Technology Assessment programme were obtained from protocols, websites or by contacting trialists. A checklist of PIL content based on Health Research Authority (HRA) and ICH GCP Guidelines was supplemented with retention specific questions. Corresponding protocols were also evaluated to cross reference trial specific procedures with information communicated to patients.ResultsPIL frequently reiterated the patient’s right to withdraw at any time (n = 49, 98%), without having to give a reason and without penalty (n = 45, 90%). However, few informed patients they may be asked to give a withdrawal reason where willing (n = 6, 12%). Statements about the value of retention were infrequent (n = 8, 16%). Consent documents failed to include key content that might mitigate withdrawals, such as the need for treatment equipoise (n = 3, 6%). Nearly half the trials in the cohort (n = 23, 46%) wanted to continue to collect outcome data if patients withdraw. However, in 70% of PIL using prospective consent, withdrawal was described in generic terms leaving patients unaware of the difference between stopping treatment and all trial involvement. Nineteen (38%) trials offered withdrawing patients the option to delete existing data.ConclusionsWithdrawal and retention is poorly described within PIL and addressing this might positively impact levels of patient attrition, reducing missing data. Consent information is unbalanced, focussing on patient’s rights to withdraw without accompanying information that promotes robust consent and sustained participation. With many citing altruistic reasons for participation it is essential that PIL include more information on retention and clarify withdrawal terminology so patients are aware of how they can make a valuable contribution to clinical studies. There is a need to determine how retention can be described to patients to avoid concerns of coercion. Future research is needed to explore whether the absence of information about retention at the time of consent is impacting attrition.

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Section: Discussionmentioning

confidence: 99%

Reducing attrition within clinical trials: The communication of retention and withdrawal within patient information leaflets

et al. 2018

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“…The CONSORT statement expects reporting of the number of participants who were randomly assigned and the number of participants in each arm included in each analysis . Surveys have shown that 95% of trials in major medical journals report some missing outcome data and 94% of palliative care trials report the number of participants not included in the primary outcome analysis . Systematic reviews have lower rates of reporting numbers of participants with missing data—47% of Cochrane reviews and 7% of non‐Cochrane reviews …”

Section: Meta‐analysis With Missing Datamentioning

confidence: 99%

Dealing with missing outcome data in meta‐analysis

Mavridis

White

2019

Research Synthesis Methods

Self Cite

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Missing data result in less precise and possibly biased effect estimates in single studies. Bias arising from studies with incomplete outcome data is naturally propagated in a meta‐analysis. Conventional analysis using only individuals with available data is adequate when the meta‐analyst can be confident that the data are missing at random (MAR) in every study—that is, that the probability of missing data does not depend on unobserved variables, conditional on observed variables. Usually, such confidence is unjustified as participants may drop out due to lack of improvement or adverse effects. The MAR assumption cannot be tested, and a sensitivity analysis to assess how robust results are to reasonable deviations from the MAR assumption is important. Two methods may be used based on plausible alternative assumptions about the missing data. Firstly, the distribution of reasons for missing data may be used to impute the missing values. Secondly, the analyst may specify the magnitude and uncertainty of possible departures from the missing at random assumption, and these may be used to correct bias and reweight the studies. This is achieved by employing a pattern mixture model and describing how the outcome in the missing participants is related to the outcome in the completers. Ideally, this relationship is informed using expert opinion. The methods are illustrated in two examples with binary and continuous outcomes. We provide recommendations on what trial investigators and systematic reviewers should do to minimize the problem of missing outcome data in meta‐analysis.

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“…However, even for palliative care drug trials of short duration (4 weeks), attrition has been shown to be high, with only 40% of participants achieving the primary end point in a trial of pregabalin for cancerinduced bone pain [5]. A review of 108 RCTs of palliative care interventions found that the reason for missing data was unclassified in 53%, recorded as loss to follow-up or withdrawal with no further details of the underlying reason [18]. Meta-ethnographic review has identified five themes which may influence nonretention in trials:…”

Section: Introductionmentioning

confidence: 99%

What influenced people with chronic or refractory breathlessness and advanced disease to take part and remain in a drug trial? A qualitative study

Lovell

Etkind

Maddocks

et al. 2020

Trials

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Background: Recruitment and retention in clinical trials remains an important challenge, particularly in the context of advanced disease. It is important to understand what affects retention to improve trial quality, minimise attrition and reduce missing data. We conducted a qualitative study embedded within a randomised feasibility trial and explored what influenced people to take part and remain in the trial. Methods: We conducted a qualitative study embedded within a double-blind randomised trial (BETTER-B[Feasibility]: BETter TreatmEnts for Refractory Breathlessness) designed using a person-centred approach. Participants with cancer, chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), or chronic heart failure (CHF), with a modified Medical Research Council dyspnoea scale grade of 3/4 were recruited from three UK sites. A convenience subsample completed qualitative interviews after the trial. Interviews were analysed using thematic analysis. Results were considered in relation to the core elements of person-centred care and our model of the person-centred trial. Results: In the feasibility trial 409 people were screened for eligibility, and 64 were randomised. No participant was lost to follow-up. Twenty-two participants took part in a qualitative interview. Eleven had a diagnosis of COPD, 8 ILD, 2 CHF and 1 lung cancer. The participants' median age was 71 years (range 56-84). Sixteen were male. Twenty had completed the trial, and two withdrew due to adverse effects. The relationship between patient and professional, potential for benefit, trial processes and the intervention all influenced the decision to participate in the trial. The relationship with the research team and continuity, perceived benefit, and aspects relating to trial processes and the intervention influenced the decision to remain in the trial. Conclusions: In this feasibility trial recruitment targets were met, attrition levels were low, and aspects of the personcentred approach were viewed positively by trial participants. Prioritisation of the relationship between the patient and professional; person-centred processes, including home visits, assistance with questionnaires, and involvement of the carer; and enabling people to participate by having processes in line with individual capabilities appear to support recruitment and retention in clinical trials in advanced disease. We recommend the integration of a person-centred approach in all clinical trials.

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Quality of missing data reporting and handling in palliative care trials demonstrates that further development of the CONSORT statement is required: a systematic review

Cited by 39 publications

References 43 publications

Reducing attrition within clinical trials: The communication of retention and withdrawal within patient information leaflets

Reducing attrition within clinical trials: The communication of retention and withdrawal within patient information leaflets

Dealing with missing outcome data in meta‐analysis

What influenced people with chronic or refractory breathlessness and advanced disease to take part and remain in a drug trial? A qualitative study

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