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Closed-system drug-transfer devices plus safe handling of hazardous drugs versus safe handling alone for reducing exposure to infusional hazardous drugs in healthcare staff

  • New
  • Review
  • Intervention

Authors


Abstract

Background

Occupational exposure to hazardous drugs can decrease fertility and result in miscarriages, stillbirths, and cancers in healthcare staff. Several recommended practices aim to reduce this exposure, including protective clothing, gloves, and biological safety cabinets ('safe handling'). There is significant uncertainty as to whether using closed-system drug-transfer devices (CSTD) in addition to safe handling decreases the contamination and risk of staff exposure to infusional hazardous drugs compared to safe handling alone.

Objectives

To assess the effects of closed-system drug-transfer of infusional hazardous drugs plus safe handling versus safe handling alone for reducing staff exposure to infusional hazardous drugs and risk of staff contamination.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, OSH-UPDATE, CINAHL, Science Citation Index Expanded, economic evaluation databases, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov to October 2017.

Selection criteria

We included comparative studies of any study design (irrespective of language, blinding, or publication status) that compared CSTD plus safe handling versus safe handling alone for infusional hazardous drugs.

Data collection and analysis

Two review authors independently identified trials and extracted data. We calculated the risk ratio (RR) and mean difference (MD) with 95% confidence intervals (CI) using both fixed-effect and random-effects models. We assessed risk of bias according to the risk of bias in non-randomised studies of interventions (ROBINS-I) tool, used an intracluster correlation coefficient of 0.10, and we assessed the quality of the evidence using GRADE.

Main results

We included 23 observational cluster studies (358 hospitals) in this review. We did not find any randomised controlled trials or formal economic evaluations. In 21 studies, the people who used the intervention (CSTD plus safe handling) and control (safe handling alone) were pharmacists or pharmacy technicians; in the other two studies, the people who used the intervention and control were nurses, pharmacists, or pharmacy technicians. The CSTD used in the studies were PhaSeal (13 studies), Tevadaptor (1 study), SpikeSwan (1 study), PhaSeal and Tevadaptor (1 study), varied (5 studies), and not stated (2 studies). The studies' descriptions of the control groups were varied. Twenty-one studies provide data on one or more outcomes for this systematic review. All the studies are at serious risk of bias. The quality of evidence is very low for all the outcomes.

There is no evidence of differences in the proportion of people with positive urine tests for exposure between the CSTD and control groups for cyclophosphamide alone (RR 0.83, 95% CI 0.46 to 1.52; I² = 12%; 2 studies; 2 hospitals; 20 participants; CSTD: 76.1% versus control: 91.7%); cyclophosphamide or ifosfamide (RR 0.09, 95% CI 0.00 to 2.79; 1 study; 1 hospital; 14 participants; CSTD: 6.4% versus control: 71.4%); and cyclophosphamide, ifosfamide, or gemcitabine (RR not estimable; 1 study; 1 hospital; 36 participants; 0% in both groups).

There is no evidence of a difference in the proportion of surface samples contaminated in the pharmacy areas or patient-care areas for any of the drugs except 5-fluorouracil, which was lower in the CSTD group than in the control (RR 0.65, 95% CI 0.43 to 0.97; 3 studies, 106 hospitals, 1008 samples; CSTD: 9% versus control: 13.9%).

The amount of cyclophosphamide was lower in pharmacy areas in the CSTD group than in the control group (MD −49.34 pg/cm², 95% CI −84.11 to −14.56, I² = 0%, 7 studies; 282 hospitals, 1793 surface samples). Additionally, one interrupted time-series study (3 hospitals; 342 samples) demonstrated a change in the slope between pre-CSTD and CSTD (3.9439 pg/cm², 95% CI 1.2303 to 6.6576; P = 0.010), but not between CSTD and post-CSTD withdrawal (−1.9331 pg/cm², 95% CI −5.1260 to 1.2598; P = 0.20). There is no evidence of difference in the amount of the other drugs between CSTD and control groups in the pharmacy areas or patient-care areas.

None of the studies report on atmospheric contamination, blood tests, or other measures of exposure to infusional hazardous drugs such as urine mutagenicity, chromosomal aberrations, sister chromatid exchanges, or micronuclei induction.

None of the studies report short-term health benefits such as reduction in skin rashes, medium-term reproductive health benefits such as fertility and parity, or long-term health benefits related to the development of any type of cancer or adverse events.

Five studies (six hospitals) report the potential cost savings through the use of CSTD. The studies used different methods of calculating the costs, and the results were not reported in a format that could be pooled via meta-analysis. There is significant variability between the studies in terms of whether CSTD resulted in cost savings (the point estimates of the average potential cost savings ranged from (2017) USD −642,656 to (2017) USD 221,818).

Authors' conclusions

There is currently no evidence to support or refute the routine use of closed-system drug transfer devices in addition to safe handling of infusional hazardous drugs, as there is no evidence of differences in exposure or financial benefits between CSTD plus safe handling versus safe handling alone (very low-quality evidence). None of the studies report health benefits.

Well-designed multicentre randomised controlled trials may be feasible depending upon the proportion of people with exposure. The next best study design is interrupted time-series. This design is likely to provide a better estimate than uncontrolled before-after studies or cross-sectional studies. Future studies may involve other alternate ways of reducing exposure in addition to safe handling as one intervention group in a multi-arm parallel design or factorial design trial. Future studies should have designs that decrease the risk of bias and enable measurement of direct health benefits in addition to exposure. Studies using exposure should be tested for a relevant selection of hazardous drugs used in the hospital to provide an estimate of the exposure and health benefits of using CSTD. Steps should be undertaken to ensure that there are no other differences between CSTD and control groups, so that one can obtain a reasonable estimate of the health benefits of using CSTD.

Plain language summary

Closed-system drug-transfer devices for reducing exposure to infusional hazardous medicines in healthcare staff

Some medicines – whether given as tablets or as a drip through the veins – are hazardous to the healthcare staff who handle them. Patients receive infusional hazardous medicines through the veins as treatment for serious diseases like cancer. When healthcare staff are exposed to these medicines, they can decrease their fertility and result in miscarriages, stillbirths, and cancers. Several recommended practices can reduce healthcare staff exposure to these hazardous medicines. These include protective clothing, gloves, and special cabinets where staff can prepare the hazardous medicines prior to giving them to patients. Together, these practices constitute 'safe handling'. A closed-system drug-transfer device (CSTD) is a device system that mechanically prevents the escape of hazardous drug outside the system.

What is the aim of this review?

There is significant uncertainty as to whether using CSTD in addition to safe handling decreases the exposure and risk of staff contamination to hazardous medicines compared to safe handling alone. We sought to resolve this issue by searching for existing studies on the topic.

Key messages

Based on very low-quality evidence, there is currently no evidence for or against adding CSTD to safe handling of hazardous medicines. Further well designed studies are necessary.

What was studied in the review?

We included all types of studies that compared CSTD plus safe handling ('CSTD group') and safe handling alone ('control group').

What are the main results of the review?

We included 23 studies (358 hospitals) in this review, none of which used the gold standard study design (randomised controlled trials) or explored a treatment's value for money. In 21 studies, the people who used the CSTD and safe handling were pharmacists or pharmacy technicians. Nineteen studies provide information that could be included for this study.

There is no evidence of any benefit for using CSTD in the indirect measures of exposure such as the presence of the hazardous drug in the urine of the healthcare professionals. There is no evidence that the contamination of surfaces or the floor with most hazardous medicines was decreased by the use of CSTD. There is significant variability between the studies in terms of whether the use of CSTD resulted in cost savings, with some studies reporting increased costs and others reporting decreased costs after introducing CSTD. None of the studies report on health benefits such as reduction in skin rashes, infertility, miscarriage, development of any type of cancer, or adverse events.

The overall quality of evidence is very low for all the outcomes because all the studies had one or more significant limitation in their design. Therefore, the results may not be reliable.

How up-to-date is this review?

We searched for studies up until 26 October 2017.