This review concluded that, although the evidence was of poor quality, enzyme replacement therapy appeared to improve visceral symptoms in type I Gaucher's disease. The effect on skeletal symptoms was uncertain and there was no evidence that it improved neurological complications. The extent of health benefit is uncertain. This was a good review and the authors' conclusions seem appropriate.

To investigate the clinical and cost-effectiveness of enzyme replacement therapy (ERT) in the treatment of symptomatic Gaucher's disease. Only clinical effectiveness is considered in this abstract.

MEDLINE, EMBASE, CINAHL, the Cochrane Library and the Science Citation Index were searched from inception to July/August 2004. The National Research Register (UK), ClinicalTrials.gov and Current Controlled Trials were also searched for ongoing and unpublished studies. The search terms were provided and there were no language restrictions.

Study designs of evaluations included in the review

Any primary study design with at least 10 participants was eligible for inclusion.

Specific interventions included in the review

Studies of ERT compared with a different ERT, no ERT (i.e. a before-and-after comparison), or other comparator such as imino sugar therapy, transplant therapy or splenectomy therapy, were eligible for inclusion. The majority of the included studies did not have a comparator.

Participants included in the review

Studies of people with Gaucher's disease, type I or II, were eligible for inclusion. Most of the included studies were of adults though some did include children.

Outcomes assessed in the review

Any clinical or patient-relevant outcome was eligible for inclusion. Most of the included studies assessed symptom-related surrogate markers of patient well-being such as organ volume, and haematological changes such as haemoglobin and platelet levels. Skeletal and lung involvement outcomes were also reported. Few of the studies measured clinical outcomes such as quality of life and mortality. Where reported, the length of follow-up ranged from 1 month to 9 years.

How were decisions on the relevance of primary studies made?

The papers were assessed for relevance by one reviewer and checked by a second. Any disagreements were resolved by consensus.

The criteria used to assess quality depended on the particular study design being assessed, and these were detailed in the report. Quality was assessed by one reviewer and checked by a second. Any disagreements were resolved by consensus.

The data were extracted by one reviewer and checked by a second. Any disagreements were resolved by consensus.

How were the studies combined?

The studies were combined in a narrative.

How were differences between studies investigated?

Differences between the studies were reported in tables and discussed in the text. Before-and-after data were considered separately from RCT data.

Sixty-three studies were included. There were 2 randomised controlled trials (RCTs) (n=59), 2 cohort studies, 1 case-control study, 16 case series with a comparison group and 42 case series with no comparison group.

One RCT was well designed but underpowered. This study showed a potentially beneficial effect of ERT on haemoglobin and platelet levels, and on hepatomegaly to a lesser extent. The other RCT provided only before-and-after data on the effectiveness of ERT. The remaining studies were mainly retrospective and were described as being of moderate quality at best, as they were susceptible to many biases and none had reliable comparator data. Overall, these studies consistently demonstrated improvements in haematological parameters, hepatomegaly and splenomegaly. On average, these parameters appeared to approach normality in the majority of patients after at least 1 year of treatment. There was some extremely weak evidence that ERT has a positive effect on skeletal pain, crises and fracture rate, but it may exacerbate bone density depletion. Although improvements in health-related quality of life were reported, patients on ERT continued to have reduced quality of life compared with the general population. Overall, there was considerable within- and between-study heterogeneity.

Cost estimates per quality-adjusted life-year gained ranged from £360,000 for the more aggressive disease genotype to £476,000 for the milder type; the average was £391,000. The authors pointed out that these estimates must be considered in the light of many caveats.

Although the evidence was of poor quality, there is little doubt that ERT is effective in the treatment of visceral symptoms of type I Gaucher's disease. In relation to the prevention of skeletal complications, there is uncertainty about its effectiveness and it has not been shown to be effective for neurological complications. The precise degree of health gain is uncertain.

There was a clearly stated review question and appropriate databases were searched for studies, including non-English language and unpublished studies. Appropriate methods were used to reduce error and bias in the review processes. Relevant study details were reported, study quality was assessed, and the findings of studies were considered in the context of their methodological limitations. The narrative synthesis was appropriate and clinical heterogeneity was discussed. The authors' conclusions about clinical effectiveness seem appropriate.

Practice: The authors did not state any implications for practice.

Research: The authors identified nine questions or areas for future research. However, they pointed out that, apart from the ninth, it is questionable whether within the current pricing environment in the UK such research would have a substantive impact on policy decisions, despite being of clinical interest. These nine areas/questions were as follows:

1. A validated disease severity index for type I Gaucher's disease is required.

2. What is the health-related quality of life in type I Gaucher's disease?

3. How does disease progression vary by age and genotype?

4. How does the risk of skeletal disease vary by genotype?

5. What is the effectiveness of alternative dose regimens on visceral and skeletal symptoms?

6. What is the effective of ERT on mortality?

7. Does the effectiveness of ERT vary by genotype?

8. What is the cost-effectiveness of ERT and how does it vary by genotype in type I Gaucher's?

9. What treatment strategies could be developed for children that could meet current standards of efficiency?

NHS R&D Health Technology Assessment (HTA) Programme, project number 03/64/01.

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.