Person-directed non-pharmacological interventions for preventing and treating sleepiness and sleep disturbances caused by shift work

  • Protocol
  • Intervention

Authors

  • Christine Herbst,

    1. University Hospital of Cologne, University of Cologne, Institute and Policlinic for Occupational Medicine, Environmental Medicine and Prevention Research, Cologne, Germany
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  • Thomas C Erren,

    Corresponding author
    1. University Hospital of Cologne, University of Cologne, Institute and Policlinic for Occupational Medicine, Environmental Medicine and Prevention Research, Cologne, Germany
    • Thomas C Erren, Institute and Policlinic for Occupational Medicine, Environmental Medicine and Prevention Research, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, Cologne, 50924, Germany. tim.erren@uni-koeln.de.

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  • Mikael Sallinen,

    1. Finnish Institute of Occupational Health, Centre of Expertise for Human Factors at Work, Team of Working Hours and Cognitive Ergonomics, Helsinki, Finland
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  • Lin Fritschi,

    1. University of Western Australia, Western Australian Institute for Medical Research, Crawley, West Australia, Australia
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  • Giovanni Costa,

    1. University of Milan, Department of Occupational Health, Milan, Italy
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  • Tim R Driscoll,

    1. The University of Sydney, School of Public Health, Sydney, New South Wales, Australia
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  • Russell G Foster,

    1. University of Oxford, Nuffield Department of Clinical Neurosciences; Circadian and Visual Neuroscience, Oxford, UK
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  • Melissa S Koch,

    1. University Hospital of Cologne, University of Cologne, Institute and Policlinic for Occupational Medicine, Environmental Medicine and Prevention Research, Cologne, Germany
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  • Juha Liira

    1. Finnish Institute of Occupational Health, Research and Development in Occupational Health Services, Helsinki, Finland
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Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

To assess the effects of person-directed, non-pharmacological interventions for preventing and treating sleeping and alertness problems in shift workers.

Background

Description of the condition

The International Labour Office (ILO 1990) defines working in shifts as: "a method of organization of working time in which workers succeed one another at the workplace so that the establishment can operate longer than the hours of work of individual workers." Shift work is very common. For example, according to the World Health Organisation (WHO), 15 to 20% of employees in Europe and the USA work according to some type of shift system (IARC 2010).

Shift work in general, and night-shift work in particular, increase the rate of work-related accidents (Wagstaff 2011). In addition, shift work may be associated with a variety of adverse physical and psychological problems including coronary heart disease (Puttonen 2010), cancer (Erren 2010) and depression (Driesen 2011). Established complaints among shift workers are difficulties in getting enough sleep and maintaining an acceptable level of alertness while working irregular hours, both of which may lead to an increased risk of errors and accidents (Akerstedt 2011; Landrigan 2004).

Description of the intervention

A number of strategies have been proposed to help an individual adapt to night shift work and shift changes. Pharmacological interventions such as hypnotics, (commonly knows as sleeping pills) and melatonin are the focus of another review (Liira 2012). Non-pharmacological interventions include scheduled darkness, use of bright light, use of dark goggles, napping, exercise and educational interventions. These are the focus of this review. Another approach to making shift work less disruptive is to manipulate the actual shift system, for example by changing the speed and direction of rotation. Another review will examine the effects of these interventions (Erren 2013a).

How the intervention might work

A key factor in the establishment of the sleep/wake rhythm in humans, together with the central nervous system, is melatonin secretion. Melatonin is produced in the pineal gland and is inhibited by light exposure to the retina, predominantly blue light of 460 to 480 nanometres (nm). Melatonin secretion peaks during the night, which is the habitual sleeping period. Chemically, melatonin produces drowsiness and lowers the body temperature and therefore makes it easier to fall and stay asleep (Burgess 2002; Cajochen 2010).

Bright light is thought to improve adaptation to a new work time schedule through inhibition of melatonin secretion. Bright light exposure before, after or during shifts may also help adaptation to other shift schedules (Bougrine 1998; Costa 1993; Eastman 1991; Eastman 1994). Conversely, scheduled exposure to darkness, that is, lack of light, achieved by thick curtains or dark goggles may facilitate day sleep after night shifts by preventing light from reaching the retina and inhibiting melatonin secretion (Eastman 1994; Sadeghniiat-Haghighi 2011; Sasseville 2006).

Shift workers tend to sleep less before night shifts than before daytime shifts, which adds to sleepiness during the night shifts. Night-shift workers who try to sleep when the melatonin phase declines and when the body temperature phase rises usually experience sleep episodes which are shorter and less well consolidated (Foster 2005). Educational interventions such as sleep hygiene courses address such issues and may give participants strategies to improve sleep off shift, and reduce sleepiness at work.

Napping during a longer shift is hypothesised to increase alertness (Takeyama 2005). Night-shift napping opportunities are expected to decrease subjective sleepiness and therefore to improve performance (Sallinen 1998; Smith-Coggins 2006).

Associations between physical exercise and improvements in various sleep parameters have been observed (Youngstedt 1997). Appropriately timed physical exercise may be a means to adapt to night shifts and to readapt to daytime schedules (Buxton 2003; Mistlberger 2005).

Why it is important to do this review

Shift work is very common in a number of industries. Individuals adapt differently to shift work. While there are a number of pharmacological strategies for coping with shift work, these may have adverse effects not welcomed by all individuals. Non-pharmacological strategies are believed to have fewer adverse effects. No previous systematic review has examined the effects of person-directed, non-pharmacological interventions in preventing and treating sleep disturbances caused by shift work.

Objectives

To assess the effects of person-directed, non-pharmacological interventions for preventing and treating sleeping and alertness problems in shift workers.

Methods

Criteria for considering studies for this review

Types of studies

We will include individually-randomised or cluster-randomised trials. This includes randomised cross-over trials, in which individuals eventually receive both interventions but the order in which they receive the interventions is random. We will include studies reported as full-text, those published as abstract only, and unpublished data.

We will also examine laboratory trials. We define laboratory trials as trials in which recruited individuals are subject to the intervention in a laboratory setting, not in their respective workplace. We will present data from laboratory studies in a separate table and use the data for comparison in the Discussion section but not for drawing conclusions on intervention effects.

Types of participants

We will include studies conducted with adult workers engaged in shift work schedules that include night shift work, irrespective of industry, country, age or co-morbidities, who have not actively sought help for sleep disturbances. These studies address the 'prevention of sleep disturbances' aspect of this review. We will also include studies conducted with shift workers who suffer from sleep disorders and who have sought medical assistance for them. These studies address the 'treatment of sleep disturbances' aspect of this review.

We will also include laboratory studies conducted with persons in simulated night shift work in a table in the Discussion section (see above).

Types of interventions

We will include trials comparing any person-directed, non-pharmacological intervention with any other intervention. We anticipate the following types of interventions:

Light:

  • use of bright light (˜10000 lux for 30 minutes) off shift

  • use of bright light during shift

  • use of dim light (˜100 lux) during shifts

  • use of dark goggles during shift

  • use of dark goggles off shift

Napping:

  • napping before shift

  • napping during shift

Exercise:

  • exercise during shift

  • exercise off shift

Educational interventions:

  • information about amount and timing of sleep

  • information about sleeping conditions

  • other lifestyle education (e.g. exercise, dietary information)

For the light and goggle interventions we will distinguish between timing (e.g. beginning, middle and end of night shift), wavelengths (white light versus limited range of wavelengths) and intensity (strength and duration) of light or amount of light transmitted through the goggles.

We will include studies comparing any person-directed, non-pharmacological interventions with no intervention or an alternative intervention.

Types of outcome measures

Primary outcomes

Sleep-wake disturbance associated with shift work is at the root of health problems of shift workers. In order to characterise the sleep-wake disturbance, we will include studies that have measured intervention effects with the following outcome measures:

  1. Sleep quality off shift: measured with a validated questionnaire such as the Bergen Insomnia scale (Pallesen 2008), Pittsburg Sleep Quality Index (Buysse 1989), Basic Nordic Sleep Questionnaire (Partinen 1995), Jenkins Sleep Questionnaire (Lallukka 2011), Karolinska Sleepiness Scale (Kaida 2006), relevant questions in the Standard Shift Work Index and wrist-worn actigraphy-based measures. These questionnaires measure more than just sleep quality. However we are only interested in the questions relating to sleep quality and sleep length. We will also accept sleep quality as measured in sleep diaries.

  2. Sleep length off shift: Average length of sleep based on the relevant questions in validated questionnaires (see examples above) or on sleep diaries, or wrist-worn actigraphy.

  3. Sleepiness during shift: Sleepiness measured at the beginning, middle and end of the shift. The disadvantages of sleepiness outcomes is that they are measured at specific time points and do not give us overall measures for sleepiness. Sleepiness can be operationalised as:

    1. self-rated (subjective) sleepiness measured with a validated questionnaire such as the Karolinska Sleepiness Scale (Kaida 2006), Stanford Sleepiness Scale (Herscovitch 1981; Hoddes 1972), relevant questions in the Standard Shift Work Index (Barton 1995), or other visual analogue scales, or

    2. physiological sleepiness measured by electrophysiological methods while working (e.g., electroencephalogram or electro-oculogram measurement while driving a train) or by standardised physiological tests of sleepiness such as the Multiple Sleep Latency Test (Carskadon 1986), the Maintenance of Wakefulness Test (Mitler 1982) or the pupillometric assessment, or

    3. behavioural sleepiness measured as performance in a validated vigilance test such as the Psychomotor Vigilance Test (e.g. Basner 2011, Thorne 2005), the MackWorth Clock Test (Mackworth 1950), or single or multiple choice reaction time tests, or

    4. behavioural sleepiness measured as characteristics of overt behaviour that are identified through video recording methods such as an Observer Rating of Drowsiness (e.g. Wierwille 1994), or PERCLOS (percentage of eyelid closure) (Dinges 1998; Sommer 2010).

Fatigue usually refers to exhaustion or tiredness due to long-lasting exertion. However, because there are some differences in the use of these terms in different countries (e.g. between Europe and Australia), we will also include fatigue as an outcome measure when it is used as a measure of sleepiness at work. Therefore, we will include studies measuring fatigue at any moment during the shift as a self-reported outcome measured with a validated questionnaire or interview.

Secondary outcomes

In studies that report primary outcomes for this review we will examine the following secondary outcomes:

  • costs for lighting interventions (e.g. initial and running costs of the lighting equipment),

  • costs for napping interventions (e.g. number of staff and costs for covering the time when individuals sleep).

A full cost-effectiveness analysis is beyond the scope of this review, as it would require information not only on our primary outcomes and their 'value' (e.g. willingness to pay) but also of potential adverse effects of shift systems such as errors or injuries and their costs and 'values'. Errors and injuries in shift workers are being evaluated in another protocol (Ker 2009).

Search methods for identification of studies

Electronic searches

We will search the following databases:

  1. MEDLINE (Ovid)

  2. EMBASE (Embase.com)

  3. Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library)

  4. Web of Knowledge (http://isiknowledge.com/ )

  5. http://www.opengrey.eu/

  6. PsycINFO (http://search.ebscohost.com/)

  7. ProQuest Dissertations & Theses (http://www.proquest.co.uk)

  8. NIOSHTIC (OSH-UPDATE);

  9. NIOSHTIC-2 (OSH-UPDATE);

  10. HSELINE (OSH-UPDATE);

  11. CISDOC (OSH-UPDATE);

We present search strategies for the first six databases as Appendix 1; Appendix 2; Appendix 3; Appendix 4; Appendix 5 and Appendix 6. As we will conduct another Cochrane review assessing the effects of shift schedule interventions (Erren 2013a) in conjunction with this one, we will run only one joint systematic search to avoid needless duplication of work. We will search Proquest using subject headings and keywords only.

Since the search term 'shift' alone leads to a very high number of citations, we have included many relevant combinations of the term 'shift' with other terms used to describe specific shifts. Examples are shift work, night shift, shift schedule and graveyard shift. We also account for terms that describe shift work, but do not use the word 'shift' such as duty time or hours (e.g. transport industry), rota (medicine) or the 4-day week alias compressed work week used to denote a series of 12-hour shifts. The search is limited by terms for different outcomes or types of interventions. Since only abstracts are searched, we have included terms near, but not exactly covered by the inclusion criteria. A second limitation is by type of trial (not for all databases).

Searching other resources

We will check reference lists of all primary studies and review articles for additional references. We will contact experts in the field to identify additional unpublished materials. We will search the conference proceedings of the biannual symposium on shift and night work. We will search the World Health Organisation Trial Register (www.who.int/ictrp/) as well as the most important trial registers within this register directly (www.clinicaltrials.gov, https://www.clinical trialsregister.eu/).

Data collection and analysis

Selection of studies

Two review authors (CH, MK) will independently screen titles and abstracts of all the studies we identify as a result of the search and code them as 'retrieve' (eligible or potentially eligible/unclear) or 'do not retrieve'. We will retrieve the full-text study reports and two review authors (CH, MK) will independently screen them for inclusion. They will also identify and record reasons for the exclusion of ineligible studies. We will resolve any disagreement through discussion or, if required, we will consult a third person (TE). We will identify and exclude duplicates and collate multiple reports of the same study so that we include studies rather than reports of studies in the review. We will record the selection process in sufficient detail to complete a PRISMA flow diagram and 'Characteristics of excluded studies' table. We will also seek to obtain further information from the study authors when a paper is found to contain insufficient information to enable us to reach a decision on eligibility.

Data extraction and management

Two review authors (CH, MK) will independently extract data from each of the included trials. We will extract the following information and present it in the review:

  • methods: type of trial (randomised controlled trial or cluster randomised trial, randomised cross-over trial), allocation, inclusion criteria, statistical analysis,

  • basic information: country, dates of study (beginning and end of allocation or study), duration of study, number of participants, number of participants evaluated, information about shift schedules,

  • basic information about the participants: age, sex, occupations, chronotype (morningness-eveningness score or similar),

  • intervention: details of interventions being compared, other interventions performed at the same time,

  • which outcomes were measured, their definitions, which outcomes are reported,

  • outcome data for the outcomes relevant to this systematic review, and

  • funding for trial, and notable conflicts of interest of trial authors.

For randomised laboratory studies we will briefly extract the following:

  • inclusion criteria,

  • details of the interventions compared, including any interventions performed at the same time in both groups,

  • number of participants,

  • country and duration of the trial,

  • which outcomes were measured and how, and

  • results of outcomes relevant to this review.

Assessment of risk of bias in included studies

Two review authors per study (CH, MK, TD, RF, LF, JL, MS) will independently assess the risk of bias of the included studies. We will consult a third review author (TE) when disagreements occur, to make the final judgment. If information is absent for evaluation of the methodological criteria, we will contact the trial authors to request additional information. Where possible, we will use quotes from the text to support our judgements about the individual 'Risk of bias' items.

We will use the 'Risk of bias' tool described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011) as implemented in Review Manager 5 (RevMan 2012). We will rate each domain as having a high, low or unclear risk of bias. We will rate a domain as having an unclear risk of bias if there is insufficient information to evaluate the domain.

We will evaluate the following domains (taken, added to, and modified where applicable from Higgins 2011):

  1. random sequence generation:

    1. We will consider trials to have a low risk of bias if they describe a random element in sequence generation such as:

      1. using a random number table,

      2. using a computer random number generator,

      3. coin tossing,

      4. shuffling cards or envelopes,

      5. throwing dice,

      6. drawing lots,

      7. or minimisation.

    2. We will consider trials to have a high risk of bias if the authors describe using:

      1. odd or even date of birth,

      2. or a rule based on e.g. work record number.

  2. allocation concealment:

    1. We will consider trials to have a low risk of bias if they report:

      1. central allocation (including telephone, web-based and pharmacy-controlled randomisation),

      2. or sequentially-numbered, opaque, sealed envelopes.

    2. We will consider trials to have a high risk of bias if they report using:

      1. an open random allocation schedule (e.g. a list of random numbers), or assignment envelopes without appropriate safeguards (e.g. if envelopes were unsealed or non­opaque or not sequentially numbered),

      2. alternation or rotation,

      3. date of birth or record number, or

      4. any other explicitly unconcealed procedure.

  3. blinding of participants and personnel:

    1. We will consider trials to have a low risk of bias when:

      1. the blinding of participants and key study personnel was ensured and it is unlikely that the blinding could have been broken, or

      2. authors do not report about blinding or report lack of or incomplete blinding, but we judge that the outcome is not likely to be influenced by lack of blinding.

    2. We will consider trials to have a high risk of bias when:

      1. there was no blinding or incomplete blinding, and the outcome is likely to be influenced by lack of blinding, or

      2. authors attempted to blind participants and personnel, but it is likely that the blinding could have been broken, and the outcome is likely to be influenced by lack of blinding.

  4. blinding of outcome assessors (evaluated for each outcome separately)

    1. We will consider trials to have a low risk of bias if:

      1. there is no blinding of outcome assessment, but the review authors judge that the outcome measurement is not likely to be influenced by lack of blinding, or

      2. blinding of outcome assessment is ensured, and it is unlikely that the blinding could have been broken.

    2. We will consider trials to have a high risk of bias if:

      1. there is no blinding of outcome assessment, and the outcome measurement is likely to be influenced by lack of blinding, or

      2. there is blinding of outcome assessment, but it is considered likely that the blinding could have been broken, and the outcome measurement is likely to be influenced by lack of blinding.

  5. incomplete outcome data (evaluated for each outcome separately)

    1. We will consider trials to have a low risk of bias if:

      1. there are no missing outcome data,

      2. reasons for missing outcome data are unlikely to be related to true outcome,

      3. missing outcome data are balanced in numbers across intervention groups, with similar reasons for missing data across groups,

      4. in dichotomous outcome data, the proportion of missing outcomes compared with the observed event risk is not large enough to have a clinically-relevant impact on the intervention effect estimate,

      5. in continuous outcome data, a plausible effect size (difference in means or standardised difference in means) among missing outcomes is not large enough to have a clinically-relevant impact on observed effect size, or

      6. missing data have been imputed using appropriate methods.

    2. We will consider trials to have a high risk of bias if:

      1. the reason for missing outcome data is likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups,

      2. in dichotomous outcome data, the proportion of missing outcomes compared with observed event risk is large enough to induce clinically-relevant bias in the intervention effect estimate,

      3. in continuous outcome data, the plausible effect size (difference in means or standardised difference in means) among missing outcomes is large enough to induce clinically-relevant bias in observed effect size,

      4. ‘as-treated’ analysis done with substantial departure of the number of participants assigned at randomisation (or beginning of the trial),

      5. there is potentially inappropriate application of simple imputation, or

      6. in cluster randomised trials loss of full clusters is likely to introduce bias.

  6. selective outcome reporting

    1. We will consider trials to have a low risk of bias if:

      1. the study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specified way,

      2. or the study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified (convincing text of this nature may be uncommon).

    2. We will consider trials to have a high risk of bias if:

      1. not all of the study’s pre-specified primary outcomes have been reported,

      2. one or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. sub scales) that were not pre-specified,

      3. one or more reported primary outcomes were not pre-specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect),

      4. one or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta-analysis, or

      5. the study report fails to include results for a key outcome that would be expected to have been reported for such a study.

  7. outcome reliable or objectively measured (for each of the outcomes relevant to the review)

    1. We will consider the outcomes to have a low risk of bias if the outcome is measured objectively (e.g. psychomotor vigilance test) or two or more raters have an agreement > 90% or kappa => 0.8.

    2. We will consider the outcomes to have a high risk of bias if two or more raters have an agreement < 90% or kappa < 0.8.

  8. other sources of bias. We will mention any other sources of bias identified in this field.

Randomised cross-over trials

We will assess all items for randomised controlled trials and in addition we will assess the following domain. We will report 'unclear' risk of bias if there is insufficient information to evaluate the domain.

  • applicability of the design for every outcome.

    • We will consider studies to be at low risk of bias if:

      • the interaction between the order of interventions and outcome was examined and no statistically significant interaction was identified, or

      • we believe the outcome to be independent of the order of treatments, for example if the wash-out period is long enough.

    • We will consider trials to be of high risk of bias if:

      • an interaction between order of interventions and outcome was identified in the analysis, or

      • we judge the outcome measure to be influenced by the order of treatments, for example if the wash-out period is very short.

Assessment of bias in conducting the systematic review

We will conduct the review according to this published protocol and report any deviations from it in the 'Differences between protocol and review' section of the systematic review.

Measures of treatment effect

We will enter the outcome data for each study into the data tables in RevMan (RevMan 2012). We will enter data as point estimates, standardised mean differences (SMDs) and their standard deviation (SD) when multiple scales are mixed, or mean and SD for continuous outcomes when the same scale is used. Should authors have dichotomised the relevant continuous outcomes we will use the data types presented by the authors if we are unable to obtain the data as continuous data. If only effect estimates and their 95% confidence intervals (CIs) or standard errors are reported in studies we will enter these data into RevMan using the generic inverse variance method. When the results cannot be entered in either way, we will enter them into Additional tables. We will reverse the scoring of scales if needed, so that a high score will denote the same direction (good or bad) in all outcomes. We will not mix different study designs. We will use STATA for calculations not possible within RevMan.

Unit of analysis issues

For studies that employ a cluster-randomised design and report sufficient data to be included in the meta-analysis but do not make an allowance for the design effect, we will calculate the design effect based on the methods described in chapter 16.3.6 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Should no reliable estimate of the intra-cluster correlation coefficient (ICC) be available from the literature but the other data be available, we will include the trial using an ICC of 0.1 . Currently the authors are unaware of ICCs for trials in shift workers. Of published ICCs, we deem the ones from the Health Services Research Unit (ICC Database) most applicable to trials in shift workers. The ICCs range from 0 to 0.32, with most coefficients being below 0.1. Higgins 2011

Dealing with missing data

We will contact trial authors to obtain data not found in their reports that are needed for the assessment of risk of bias, or data for outcomes relevant to this systematic review. We will use all reports of trials in order to obtain missing data, including presentations, if found. We will use the methods presented in the Cochrane Handbook (Higgins 2011) chapter 7.7.3.3 to calculate statistics (e.g. standard deviations or correlation coefficients) that can be calculated from other values.

If possible, we will use intention-to-treat analyses in randomised trials. The following information may be of relevance in order to assess the impact of missing data: distribution by intervention group and by baseline variables (age, sex, etc) as well as by responses on a first questionnaire (when multiple questionnaires are used). We will examine reasons for drop-out and missing data if these data are available. We will record the methods study authors used for dealing with missing data.

Missing data may be a strong source of bias. Sensitivity analyses will examine the effect of trials with high and low numbers of missing data.

We aim not to undertake imputation of data. The extent of missing data may be so severe that even imputation may lead to biased estimates of the effect.

Assessment of heterogeneity

Within each comparison of interventions and each outcome, we will assess the homogeneity of the results of included studies based on similarity of interventions, populations, exact outcome definitions, outcome timing and follow-up.

We will separately analyse studies in shift workers and persons with shift work disorder. We will explore other differences in population in subgroup analyses (see Subgroup analysis and investigation of heterogeneity).

We will consider studies to be similar enough to be combined with regard to outcome if they use the same outcome (e.g. sleepiness) measured at a similar time with regard to the shifts examined. All of the different ways of measuring one outcome will be considered similar enough for the primary analysis. Differences in outcome definitions will be examined in subgroup analyses. When a study reports an outcome in more than one way we will use the subjective measure of sleepiness, sleep quality from sleep diaries and sleep length from sleep diaries in the main analysis.

We anticipate several categories of interventions (light, goggles, exercise, educational interventions). For light or goggle interventions we will consider the time of day, duration of light, strength and wavelengths of light (or similar for goggles). We will consider educational interventions to be similar enough provided they address similar topics (e.g. sleep times with regard to shift, sleep conditions, exercise) and have a similar duration. We will combine all exercise interventions.

In addition, we will test for statistical heterogeneity by means of the Chi2 test as implemented in the forest plot in Review Manager 5 software (RevMan 2012). We will use a significance level of P < 0.1 to indicate whether there is a problem with heterogeneity. Moreover, we will quantify the degree of heterogeneity using the I2 statistic, where an I2 value of 25% to 50% indicates a low degree of heterogeneity, 50% to 75% a moderate degree of heterogeneity and > 75% a high degree of heterogeneity (Higgins 2011). If we identify substantial heterogeneity we will report it and explore possible causes by prespecified subgroup analysis.

Assessment of reporting biases

We will reduce the effect of reporting bias by including studies and not publications in order to avoid the introduction of duplicated data (i.e. two articles could represent duplicate publications of the same study). Following the Cho 2000 statement on redundant publications, we will attempt to detect duplicate studies and, if more articles report on the same study, we will extract data only once. We will prevent location bias by searching across multiple databases. We will prevent language bias by not excluding any article based on language. We will construct and analyse funnel plots to assess the likelihood of publication bias if more than five trials are included in a comparison. We will use the test proposed by Egger 1997 if we include more than 10 trials in a comparison. We will assess selective reporting of outcomes in sensitivity analyses (see Sensitivity analysis).

Data synthesis

We will pool data from studies judged to be homogeneous enough (see Assessment of heterogeneity) using Review Manager 5 software. If possible, we will combine studies using incidence data or for trials reporting continuous data, standardised mean differences (SMDs). To make the SMDs more readily interpretable for clinicians, we will then recalculate the pooled SMD into a mean difference by multiplying the SMD by the median standard deviation taken from included studies using the preferred scale in question. We will meta-analyse sleep length as mean differences.

When studies are found to be heterogenous (i.e. dissimilar in terms of intervention, outcome, population or follow-up time) we expect to find them also statistically heterogenous. Therefore, we consider a random-effects model to be more appropriate for meta-analysis. All estimates will include a 95% CI. For analyses not possible within Review Manager we will use STATA or other statistical software.

We will use the GRADE approach as described in theCochrane Handbook (Higgins 2011) and as implemented in the GRADEPro 3.2 software (GRADEpro 2008) to present the quality of evidence and 'Summary of findings' tables.

The downgrading of the quality of a body of evidence for a specific outcome will be based on five factors:

  1. Limitations of study.

  2. Indirectness of evidence.

  3. Inconsistency of results.

  4. Imprecision of results.

  5. Publication bias.

The GRADE approach specifies four levels of quality (high, moderate, low and very low).

Subgroup analysis and investigation of heterogeneity

If we find several studies that have investigated similar interventions and have used the same or very similar outcome measures at the same or similar follow-up times, we will conduct the following subgroup analyses:

  1. Chronotype (or similar). Rationale: sleep-wake disturbances on, for example, night shifts are different for people with different chronotypes or different chronobiological propensity (Erren 2013).

  2. Differences in the intervention: Details of, for example, light scheduling may influence sleepiness. occupational settings or branches of industry (e.g. hospital staff). Rationale: work differs in different industries by physical and psychological strain, thus affecting sleepiness for example.

  3. Different ways of measuring the same outcome. Rationale: for example, actigraphy for sleep length may be more exact, yet limited to a smaller time range than sleep diaries, which give a better overall picture.

  4. Mean or median age. Rationale: older shift workers have more experience with shift work and may have adapted better to shift work or may be persons whose chronotypes are better suited to shift work, as people not suited to shift work will have left shift work (selection effects)

Sensitivity analysis

If possible we will conduct the following sensitivity analyses:

  • each of the domains of the 'Risk of bias' assessment; for selective outcome reporting each outcome by selective outcome reporting of the other outcomes

  • different assumptions for imputation of missing data, different proportions of missing data

  • different assumptions for ICCs (for cluster-randomised trials)

  • fixed-effect model.

Acknowledgements

We thank Dr. Kathrin Bauer for the idea of conducting a Cochrane Review within the Department of Occupational Medicine in Cologne. We thank Leena Isotalo for advice and help with the search strategy. We also thank the Managing Editor Jani Ruotsalainen and Coordinating Editor Jos Verbeek from the Cochrane Occupational Safety and Health Review Group for their help.

Appendices

Appendix 1. MEDLINE search strategy

1. exp Chronobiology Disorders/
2. exp Sleep Disorders/
3. exp Circadian Rhythm/
4. exp "wounds and injuries"/ OR occupational injuries/
5. (errors OR incidents OR accidents OR mistakes OR safety).tw.
6. Death, Sudden, Cardiac/ OR Death, Sudden/ OR death?.tw. OR Death/
7. exp "costs and cost analysis"/
8. (econom$ OR cost OR costs).tw.
9. (chronotherapy OR light OR daylight OR dark OR darkness).tw.
10. exp sleep disorders, intrinsic/ OR exp "sleep initiation and maintenance disorders"/
11. (sleep OR sleepiness OR circadian OR vigilance OR altertness OR alert OR wakefulness OR drowsiness OR fatigue OR insomnia OR hypersomnolence OR dyssomnia OR eveningness OR morningness OR "concentration difficulties" OR attentiveness OR arousal OR performance OR vigilance OR vigilant).tw.
12. (nap OR napping OR rest OR resting).tw.
13. 1 OR 2 OR 3 OR 4 OR 5 OR 6 OR 7 OR 8 OR 9 OR 10 OR 11 OR 12
14. ((shift OR shifts) adj1 (rota OR system OR systems OR schedul* OR hours OR time OR pattern$ OR cycle OR extend$ OR evening OR late OR roster OR early OR weekend OR twilight OR graveyard OR night$ OR split OR non-standard OR "non standard" OR flex$ OR turnaround OR continuous OR rotat$)).tw.
15. (day adj2 schedule?).tw.
16. (rota OR roster OR 'day week' OR flexitime OR 'hours of work' OR nightshift* OR shiftwork*).tw.
17. ((work$ OR duty) adj1 (shift OR shifts OR rota OR system OR systems OR schedul* OR hours OR time OR pattern$ OR cycle OR extend$ OR evening OR late OR roster OR early OR weekend OR twilight OR graveyard OR night* OR split OR non-standard OR "non standard" OR flex$ OR turnaround OR continuous OR rotation$)).tw.
18. ((backward OR forward OR rapid OR slow OR rapidly OR slowly OR advancing OR delaying) adj1 (rotation OR rotate OR rotating)).tw.
19. (rota OR roster OR duty OR shift OR shifts OR shiftwork OR hours OR week OR work).mp.
20. 18 and 19
21. 14 OR 15 OR 16 OR 17 OR 20
22. (randomized controlled trial OR controlled clinical trial).pt. OR randomized.ab. OR placebo.ab. OR drug therapy.fs. OR randomly.ab. OR trial.ab. OR groups.ab.
23. (effect* OR controll* OR control OR controls* OR controli* OR controle* OR controla* OR evaluation* OR program*).tw.
24. (work OR works* OR work* OR worka* OR worke* OR workg* OR worki* OR workl* OR occupation* or prevention* OR protect*).tw.
25. 24 and 23
26. (cohort OR cross sectional OR study OR survey OR questionnaire? OR diary OR diaries).tw.
27. Case-control studies/ OR cohort studies/ OR evaluation studies/ OR feasibility studies/ OR longitudinal studies/ OR program evaluation/ OR prospective studies/ OR retrospective studies/ OR exp follow-up studies/ OR exp risk Factors/ OR exp evaluation studies/ OR exp retrospective Studies OR exp chi-square distribution/ OR logistic models/ OR exp treatment outcome/ OR exp comparative studies OR cross-sectional studies/ OR multivariate analysis/
28. 22 OR 25 OR 26 OR 27
29. exp animals/ not humans.sh.
30. 28 NOT 29
31. 13 AND 21 AND 30

Appendix 2. EMBASE search strategy

1. ((work NEAR/2 hour*) OR (shift NEAR/2 work*) OR (work* NEAR/2 week) OR nightshift* OR shiftwork* OR (day NEAR/2 schedule))
2. ((rotat* NEAR/2 (backward OR forward OR rapid OR slow OR rapidly OR slowly OR advancing OR delaying)) AND (shift* OR work* OR schedule OR time OR duty OR hours OR rota OR roster))
3. (shift$ NEAR/1 (rota OR system$ OR schedul* OR hours OR time OR pattern* OR cycle OR extend* OR evening OR late OR roster OR early OR weekend OR twilight OR graveyard OR night$ OR split OR non-standard OR "non standard" OR flex$ OR turnaround OR continuous OR rotat*)
4. (shift* NEAR/2 (backward OR forward OR rapid OR slow OR rapidly OR slowly OR advancing OR delaying OR roster OR rota OR "day week"))
5. (nightshift* OR shiftwork*).tw. OR rota*?.tw. OR roster*.tw. OR 'day week'.tw.
6.exp Sleep Disorders/ OR 3. exp Circadian Rhythm/ OR exp "wounds and injuries"/ OR occupational injuries/ OR exp Death, Sudden, Cardiac/ OR Death, Sudden/ OR Death/ OR exp "costs and cost analysis"/ OR exp Chronobiology Disorders/
7. (sleep OR sleepiness OR circadian OR vigilance OR altertness OR alert OR wakefulness OR drowsiness OR fatigue OR insomnia OR hypersomnolence OR dyssomnia OR eveningness OR morningness OR "concentration difficulties" OR attentiveness OR arousal OR performance OR vigilant OR nap OR napping OR rest OR resting OR errors OR incidents OR accidents OR mistakes OR safety OR deaths OR death OR mortality OR injury OR injuries OR chronotherapy OR light OR daylight OR dark OR darkness OR econom$ OR cost OR costs).tw.
8. treatment outcome/ OR intermethod comparison/ OR major clinical study/ OR controlled study/ OR prospective study/ OR case-control study/ OR clinical article/ OR controlled study/ OR risk factor/ OR exp Follow Up/ OR outcomes research/ OR multivariate analysis/ OR retrospective study/ OR cohort analysis/ OR comparative study/ OR population research/ OR risk factors/
9. (cross adj1 sectional).tw OR compared.tw OR compares.tw. OR (cohort OR cross-sectional OR case-control OR study OR survey OR surveys OR diary OR diaries OR questionnaire? OR groups OR comparison$ OR multivariate OR risk factor$ OR effectiveness).mp.
10. 1 OR 2 OR 3 OR 4 OR 5
11. 6 OR 7
12. 8 OR 9
13. 10 AND 11 AND 12

Appendix 3. OPEN GREY

(((work NEAR/2 hour*) OR (shift NEAR/2 work*) OR (work* NEAR/2 week) OR nightshift* OR shiftwork* OR (day NEAR/2 schedule) OR ((rotat* NEAR/1 (backward OR forward OR rapid OR slow OR rapidly OR slowly OR advancing OR delaying) AND (shift* OR work* OR schedule OR time OR duty OR hours OR rota OR roster)) OR (shift$ NEAR/1 (rota OR system$ OR schedul* OR hours OR time OR pattern* OR cycle OR extend* OR evening OR late OR roster OR early OR weekend OR twilight OR graveyard OR night$ OR split OR non-standard OR "non standard" OR flex$ OR turnaround OR continuous OR rotat*)) OR (shift* NEAR/2 (backward OR forward OR rapid OR slow OR rapidly OR slowly OR advancing OR delaying OR roster OR rota OR “day week” )) AND (sleep OR sleepiness OR circadian OR vigilance OR altertness OR alert OR wakefulness OR drowsiness OR fatigue OR insomnia OR hypersomnolence OR dyssomnia OR eveningness OR morningness OR "neurocognitive performance" OR "concentration difficulties" OR attentiveness OR arousal OR performance OR vigilant OR nap OR napping OR rest OR resting OR errors OR incidents OR accidents OR mistakes OR safety OR deaths OR death OR mortality OR injury OR injuries OR chronotherapy OR light OR daylight OR dark OR darkness OR econom$ OR cost OR costs OR light OR dark OR darkness OR goggles OR exercise))

Appendix 4. PsycINFO

S1 TX ((work N2 hour*) OR (shift N2 work*) OR (work* N2 week) OR nightshift* OR shiftwork* OR (day N2 schedule))
S2 TX ((rotat* N2 (backward OR forward OR rapid OR slow OR rapidly OR slowly OR advancing OR delaying)) AND (shift* OR work* OR schedule OR time OR duty OR hours OR rota OR roster))
S3 TX (shift$ N2 (rota OR system$ OR schedul* OR hours OR time OR pattern* OR cycle OR extend* OR evening OR late OR roster OR early OR weekend OR twilight OR graveyard OR night$ OR split OR non-standard OR "non standard" OR flex$ OR turnaround OR continuous OR rotat*))
S4 TX (shift* N2 (backward OR forward OR rapid OR slow OR rapidly OR slowly OR advancing OR delaying) OR (roster OR rota) OR "day week")
S5 TX (sleep OR sleepiness OR circadian OR vigilance OR altertness OR alert OR wakefulness OR drowsiness OR fatigue OR insomnia OR hypersomnolence OR dyssomnia OR eveningness OR morningness OR "neurocognitive performance" OR "concentration difficulties" OR attentiveness OR arousal OR performance OR vigilant OR nap OR napping OR rest OR resting OR errors OR incidents OR accidents OR mistakes OR safety OR deaths OR death OR mortality OR injury OR injuries OR chronotherapy OR light OR daylight OR dark OR darkness OR econom$ OR cost OR costs)
S6 DE workday shifts
S7 DE human biological rhythms
S8 DE sleepiness
S9 DE sleep deprivation
S10 DE sleep disorders
S11 DE sleep
S12 DE physiological arousal
S13 DE fatigue
S14 DE workday shifts
S15 DE work scheduling
S16 DE performance
S17 DE occupational safety
S18 DE napping
S19 DE job performance
S20 DE wakefulness
S21 DE sleep onset
S22 DE mortality rate
S23 DE trends
S24 DE risk factors
S25 DE longitudinal studies
S26 DE follow up studies
S27 DE retrospective studies
S28 TX control OR (cross N1 sectional) OR compared OR compares OR cohort OR cross-sectional OR (case N1 control) OR study OR survey OR surveys OR diary OR diaries OR questionnaire? OR evaluation OR evaluate OR groups OR comparison$ OR multivariate OR risk factor$ OR effectiveness OR random* OR allocation OR allocate OR allocated
S29 S28 OR S27 OR S26 OR S25 OR S24 OR S23
S30 S22 OR S21 OR S20 OR S19 OR S18 OR S17 OR S16 OR S13 OR S12 OR S11 OR S10 OR S9 OR S8 OR S7 OR S5
S31 S1 OR S2 OR S3 OR S4 OR S6 OR S15
S32 S31 AND S30 AND S29

Appendix 5. Web of Knowledge

  1. TS=(work NEAR/2 hour*)

  2. TS=(shift NEAR/2 work*)

  3. TS=(work* NEAR/2 week)

  4. TS=(nightshift* OR shiftwork*)

  5. TS=(day NEAR/2 schedule*)

  6. TS=(rotat* NEAR/1 (backward OR forward OR rapid OR slow OR rapidly OR slowly OR advancing OR delaying))

  7. TS=(shift* OR work* OR schedule OR time OR duty OR hours OR rota OR roster)

  8. #6 AND #7

  9. TS=(shift$ NEAR/1 (rota OR system$ OR schedul* OR hours OR time OR pattern* OR cycle OR extend* OR evening OR late OR roster OR early OR weekend OR twilight OR graveyard OR night$ OR split OR non-standard OR "non standard" OR flex$ OR turnaround OR continuous OR rotat*))

  10. TS=(roster OR rota)

  11. TS=("day week")

  12. TS=(shift* NEAR/1 (backward OR forward OR rapid OR slow OR rapidly OR slowly OR advancing OR delaying))

  13. TS=(sleep OR sleepiness OR circadian OR vigilance OR altertness OR alert OR wakefulness OR drowsiness OR fatigue OR insomnia OR hypersomnolence OR dyssomnia OR eveningness OR morningness OR "neurocognitive performance" OR "concentration difficulties" OR attentiveness OR arousal OR performance OR vigilant OR nap OR napping OR rest OR resting OR errors OR incidents OR accidents OR mistakes OR safety OR deaths OR death OR mortality OR injury OR injuries OR chronotherapy OR light OR daylight OR dark OR darkness OR econom$ OR cost OR costs)

  14. TS=(effect* OR controll* OR control OR controls* OR controli* OR controle* OR controla* OR evaluation* OR program* OR cohort OR cross sectional OR study OR survey OR questionnaire? OR diary OR diaries OR placebo OR random* OR trial OR groups OR multivariate OR compare? OR comparison* OR risk factor?)

  15. #1 OR #2 OR #3 OR #4 OR #5 OR #8 OR #9 OR #10 OR #11 OR #12#15 AND #14 AND #13

  16. TI=(mice OR rats)

  17. #15 NOT #16

Appendix 6. Cochrane CENTRAL

#1 ((work NEAR/2 hour*) OR (shift NEAR/2 work*) OR (work* NEAR/2 week) OR nightshift* OR shiftwork* OR (day NEAR/2 schedule)):kw
#2 ((rotat* NEAR/2 (backward OR forward OR rapid OR slow OR rapidly OR slowly OR advancing OR delaying)) AND (shift* OR work* OR schedule OR time OR duty OR hours OR rota OR roster)):kw
#3 (shift$ NEAR/2 (rota OR system$ OR schedul* OR hours OR time OR pattern* OR cycle OR extend* OR evening OR late OR roster OR early OR weekend OR twilight OR graveyard OR night$ OR split OR non-standard OR "non standard" OR flex$ OR turnaround OR continuous OR rotat*)):kw
#4 (shift* NEAR/2 (backward OR forward OR rapid OR slow OR rapidly OR slowly OR advancing OR delaying) OR (roster OR rota) OR "day week"):kw
#5 MeSH descriptOR Work Schedule Tolerance explode all trees
#6 (sleep OR sleepiness OR circadian OR vigilance OR altertness OR alert OR wakefulness OR drowsiness OR fatigue OR insomnia OR hypersomnolence OR dyssomnia OR eveningness OR morningness OR "neurocognitive performance" OR "concentration difficulties" OR attentiveness OR arousal OR performance OR vigilant OR nap OR napping OR rest OR resting OR errors OR incidents OR accidents OR mistakes OR safety OR deaths OR death OR mortality OR injury OR injuries OR chronotherapy OR light OR daylight OR dark OR darkness OR econom$ OR cost OR costs):kw
#7 MeSH descriptor Sleep Phase Chronotherapy explode all trees
#8 MeSH descriptor Chronotherapy explode all trees
#9 MeSH descriptor Chronobiology Disorders explode all trees
#10 MeSH descriptor Sleep Disorders, Circadian Rhythm explode all trees
#11 MeSH descriptor Dyssomnias explode all tree
#12 MeSH descriptor Sleep Disorders, Circadian Rhythm explode all trees
#13 MeSH descriptor Sleep Initiation and Maintenance Disorders explode all trees
#14 MeSH descriptor Sleep Deprivation explode all trees
#15 MeSH descriptor Sleep Disorders, Intrinsic explode all trees
#16 MeSH descriptor Sleep Disorders explode all trees
#17 MeSH descriptor Sleep explode all trees
#18 MeSH descriptor Psychomotor Performance explode all trees
#19 MeSH descriptor Medical Errors explode all trees
#20 MeSH descriptor Mortality explode all trees
#21 MeSH descriptor Death explode all trees
#22 MeSH descriptor Wounds and Injuries explode all trees
#23 MeSH descriptor Fatigue explode all trees
#24 MeSH descriptor Economics explode all trees
#25 MeSH descriptor Cost of Illness explode all trees
#26 (#1 OR #2 OR #3 OR #4 OR #5)
#27 (#6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25)
#28 (#26 AND #27)

Contributions of authors

Christine Herbst: designing and coordinating the review, writing the protocol (based in part on the old combined protocol), designing search strategies, proofreading

Thomas C Erren: advice for all sections of the protocol, coordination of the review, proofreading

Mikael Sallinen: definitions of outcomes, proofreading

Lin E Fritschi: methodological advice, definitions of outcomes, proofreading

Giovanni Costa: proofreading

Tim R Driscoll: methodological advice, proofreading

Russell G Foster: proofreading

Melissa S Koch: proofreading

Juha Liira: conceiving the original review that was split, proofreading

Declarations of interest

Christine Herbst: Organisation and preparation of the review is one of her duties as a research assistant at the Institute and Policlinic for Occupational Medicine, Environmental Medicine and Prevention Research, University Clinic of Cologne, University Hospital of Cologne, Cologne, Germany

Thomas C Erren: none known

Mikael Sallinen: a grant outside the scope of the submitted work

Lin E Fritschi:none known

Giovanni Costa: none known.

Tim R Driscoll: none known.

Russell G Foster: His institution currently receives a grant from the Wellcome Trust "Melanopsin signalling: phototransduction, behavioural regulation and clinical relevance" Start date: 1st June 2010 for 5 years. He receives royalties from a book "Rhythms of Life: The biological clocks that control the daily lives of every living thing" and is employed for by the University of Oxford. He is a board member of the Biotechnology and Biological Sciences Research Council.

Melissa S Koch: none known.

Juha Liira: He has received the following payments linked to work on occupational health and work places: Ilmarinen (insurance company) 12000 euros for a total of five lectures on well-being at work; Research Council of Norway 1500 euros for reviewing applications submitted to the PETROMAKS research.

Ancillary