Informed consent in clinical trials in critical care: experience from the PAC-Man Study

Harvey, Sheila; Elbourne, Diana; Ashcroft, Joanne; Jones, Carys; Rowan, Kathy

doi:10.1007/s00134-006-0358-4

Cited by 55 publications

(45 citation statements)

References 20 publications

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“…On the basis of this estimation, we calculated that an enrollment of 1260 patients would have a power of 80% to detect a relative reduction of 20% in risk (absolute risk reduction, 8 percentage points) in the EGDT group, allowing for a loss to follow-up or withdrawal of 6%. 21 All analyses were performed according to the intention-to-treat principle and were prespecified in the statistical analysis plan. 22 A P value of less than 0.05 was considered to indicate statistical significance.…”

Section: Discussionmentioning

confidence: 99%

Trial of Early, Goal-Directed Resuscitation for Septic Shock

Mouncey¹,

Osborn

Power³

et al. 2015

N Engl J Med

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931

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Section: Discussionmentioning

confidence: 99%

Trial of Early, Goal-Directed Resuscitation for Septic Shock

Mouncey¹,

Osborn

Power³

et al. 2015

N Engl J Med

Self Cite

1,356

931

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“…Similarly, in a study of 240 capable and consenting survivors of critical illness, Scales et al reported that more than three-quarters (76%) of patients selected "consent by substitute prior to enrolment" as their preferred framework for inclusion in a clinical trial (56). However, while evidence suggests that few patients refuse consent retrospectively (43), there is no existing guidance in the literature or ethical frameworks about how long attempts to re-consent should be continued (13).…”

Section: Re-consentingmentioning

confidence: 99%

Ethical challenges involved in obtaining consent for research from patients hospitalized in the intensive care unit

Ecarnot¹,

Quenot²,

Besch³

et al. 2017

Ann. Transl. Med.

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Clinical research remains a vital contributor to medical knowledge, and is an established and integral part of the practice of medicine worldwide. Respect for patient autonomy and ethical principles dictate that informed consent must be obtained from subjects before they can be enrolled into clinical research, yet these conditions may be difficult to apply in real practice in the intensive care unit (ICU).A number of factors serve to complexify the consent process in critically ill patients, notably decisional incapacity of the patient due to illness or sedation. Obtaining consent for research from a designated proxy or family member, commonly termed a "surrogate decision maker" (SDM) may be difficult, since SDMs dealing with the emotional, psychological and logistic impact of a sudden hospitalisation of their lovedone are not always receptive to the idea of research or emotionally equipped to reflect rationally on the opportunities being proposed to them. In addition, time constraints and workload pressures on the attending physician may render consent opportunities unfeasible, and the resulting loss of eligible patients could represent a bias in clinical trials, or limit the generalizability of their results. Alternative procedures such as deferred or waived consent have been used in the past and may be suitable alternatives in certain conditions, provided appropriate approval from institutional review boards (IRBs) can be obtained, in accordance with existing legislation. Some of the main questions inherent to the conduct of clinical research in critically ill patients are discussed in this review.

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“…To have 90% power, with a type I error rate of 5% (two sided), to detect a 20% relative risk reduction (6.4% absolute risk reduction) from 32% in the enteral route group to 25.6% in the parenteral route group, requires a sample size of 1082 per treatment group (Stata/SE version 10.1, StataCorp LP, College Station, TX, USA). To allow 2% for crossover/protocol violation (in each direction) and 2% for loss to follow-up/withdrawal prior to 30 days (based on observed rates from the PAC-Man Study 40 ), a sample size of 1200 per treatment group (2400 total) was required. No adjustment to the sample size calculation was made to account for subgroup analyses.…”

Section: Sample Sizementioning

confidence: 99%

A multicentre, randomised controlled trial comparing the clinical effectiveness and cost-effectiveness of early nutritional support via the parenteral versus the enteral route in critically ill patients (CALORIES)

Harvey

Parrott

Harrison

et al. 2016

Health Technol Assess

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BackgroundMalnutrition is a common problem in critically ill patients in UK NHS critical care units. Early nutritional support is therefore recommended to address deficiencies in nutritional state and related disorders in metabolism. However, evidence is conflicting regarding the optimum route (parenteral or enteral) of delivery.ObjectivesTo estimate the effect of early nutritional support via the parenteral route compared with the enteral route on mortality at 30 days and on incremental cost-effectiveness at 1 year. Secondary objectives were to compare the route of early nutritional support on duration of organ support; infectious and non-infectious complications; critical care unit and acute hospital length of stay; all-cause mortality at critical care unit and acute hospital discharge, at 90 days and 1 year; survival to 90 days and 1 year; nutritional and health-related quality of life, resource use and costs at 90 days and 1 year; and estimated lifetime incremental cost-effectiveness.DesignA pragmatic, open, multicentre, parallel-group randomised controlled trial with an integrated economic evaluation.SettingAdult general critical care units in 33 NHS hospitals in England.Participants2400 eligible patients.InterventionsFive days of early nutritional support delivered via the parenteral (n = 1200) and enteral (n = 1200) route.Main outcome measuresAll-cause mortality at 30 days after randomisation and incremental net benefit (INB) (at £20,000 per quality-adjusted life-year) at 1 year.ResultsBy 30 days, 393 of 1188 (33.1%) patients assigned to receive early nutritional support via the parenteral route and 409 of 1195 (34.2%) assigned to the enteral route had died [p = 0.57; absolute risk reduction 1.15%, 95% confidence interval (CI) −2.65 to 4.94; relative risk 0.97 (0.86 to 1.08)]. At 1 year, INB for the parenteral route compared with the enteral route was negative at −£1320 (95% CI −£3709 to £1069). The probability that early nutritional support via the parenteral route is more cost-effective – given the data – is < 20%. The proportion of patients in the parenteral group who experienced episodes of hypoglycaemia (p = 0.006) and of vomiting (p < 0.001) was significantly lower than in the enteral group. There were no significant differences in the 15 other secondary outcomes and no significant interactions with pre-specified subgroups.LimitationsBlinding of nutritional support was deemed to be impractical and, although the primary outcome was objective, some secondary outcomes, although defined and objectively assessed, may have been more vulnerable to observer bias.ConclusionsThere was no significant difference in all-cause mortality at 30 days for early nutritional support via the parenteral route compared with the enteral route among adults admitted to critical care units in England. On average, costs were higher for the parenteral route, which, combined with similar survival and quality of life, resulted in negative INBs at 1 year.Future workNutritional support is a complex combination of timing, dose, duration, delivery and type, all of which may affect outcomes and costs. Conflicting evidence remains regarding optimum provision to critically ill patients. There is a need to utilise rigorous consensus methods to establish future priorities for basic and clinical research in this area.Trial registrationCurrent Controlled Trials ISRCTN17386141.FundingThis project was funded by the NIHR Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 28. See the NIHR Journals Library website for further project information.

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Informed consent in clinical trials in critical care: experience from the PAC-Man Study

Cited by 55 publications

References 20 publications

Trial of Early, Goal-Directed Resuscitation for Septic Shock

Trial of Early, Goal-Directed Resuscitation for Septic Shock

Ethical challenges involved in obtaining consent for research from patients hospitalized in the intensive care unit

A multicentre, randomised controlled trial comparing the clinical effectiveness and cost-effectiveness of early nutritional support via the parenteral versus the enteral route in critically ill patients (CALORIES)

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