SUrrogates for Mortality in cancer Screening trials (SUMS): A systematic review and meta-analysis

The SUMS study will review the literature on cancer screening trials which have looked at death rates for specific cancers. These trials cost a lot and take a very long time. We will look for outcomes that predict future cancer death but can be assessed earlier. These are known as surrogate endpoints.

Our aim is to assess how well each of these surrogate endpoints can predict cancer death. These findings will help inform the design of future trials. For trials underway, this information will help us decide which trials should continue or stop early. It will also help determine whether screening is likely to significantly reduce cancer deaths.

Find out more here

Group B Streptococcus

Warwick Screening undertook rapid reviews for the National Screening Committee about screening for Group B Strep in pregnancy. The review found that a woman may have a positive result a few weeks before labour and a negative result when she gives birth, GBS does not cause an infection in every baby- there is no way of telling which babies will be affected; screening may result in giving many women antibiotics when they do not need them, it is not known if the benefits of screening outweigh the harms for most of the population and the proportion of babies affected by disease in countries where screening is carried out is similar to that in the UK. See our publications on adverse events and bacterial load:

Universal antenatal screening for group B streptococcus may cause more harm than good | The BMJ

Adverse events in women and children who have received intrapartum antibiotic prophylaxis treatment: a systematic review | BMC Pregnancy and Childbirth | Full Text (biomedcentral.com)

Breast screening and ultrasound

Warwick Screening carried out a systematic review to find information about the reliability of different mammographic breast density measurement methods among women attending breast cancer screening. We found that reliability varied between the studies. We concluded that until more reliable methods of measuring mammographic breast density are available, there is not enough evidence to support supplemental ultrasound screening for women based on mammographic breast density measures in routine screening practice. We also looked at studies of information on cost-effectiveness of additional ultrasound in women with dense breasts and found the addition of ultrasound did not appear to be cost-effective. Find out more about this review. 

Non-Invasive Prenatal Testing using Cell Free DNA for Detection of Down, Edwards and Patau Syndromes

Warwick Screening carried out a systematic review and meta-analysis to measure the test accuracy of non-invasive prenatal testing (NIPT) for Down, Edwards and Patau syndromes using cell-free fetal DNA and identify factors affecting accuracy. We found that NIPT using cell-free fetal DNA has very high sensitivity and specificity for Down syndrome, with slightly lower sensitivity for Edwards and Patau syndrome. However, it is not 100% accurate and should not be used as a final diagnosis for positive cases. Find out more about this review.

We are also investigating the impact of financial conflicts and manufacturer involvement in the evidence base, evaluating the performance of prenatal cfDNA testing for fetal trisomies 21, 18 and 13. See the protocol here.

Antenatal screening for fetal trisomies using microarray-based cell-free DNA testing

Warwick Screening carried out a systematic review and meta-analysis to evaluate the test accuracy of non-invasive prenantal testing (NIPT) for fetal Down, Edwards and Patau syndromes using cell-free (cf) DNA analysis in maternal plasma with microarray quantitation. We found that included studies suggest that NIPT using microarray-based cfDNA testing has high sensitivity and specificity for detecting fetal Down, Edwards, and Patau syndromes. However, the evidence-base is small and at high risk of bias. Find out more about this review.

Tyrosinemia type 1

Warwick Screening carried out a systematic review into the accuracy of newborn screening for tyrosinemia type 1. Tyrosinemia type 1 is an autosomal recessive disorder of amino acid metabolism. Without treatment, death in childhood is common. Treatment with nitisinone and dietary restrictions are associated with improved outcomes; some studies suggest better outcomes when treatment begins at an asymptomatic stage. Newborn screening allows for earlier identification, but there is uncertainty regarding the test accuracy of the current method: succinylacetone measurement in dried blood spots using tandem mass spectrometry. We found that studies on earlier screening appear to be promising but further research is needed. Also, that there is some evidence from observational studies that earlier treatment with nitisinone might be beneficial but this is subject to bias. Find out more about our review on test accuracy here. Find out more about our review on treatment here.

Long-Chain 3-Hydroxyacyl CoA Dehydrogenase Deficiency (LCHADD)

Warwick Screening carried out systematic reviews into whether newborns should be screened for LCHADD. LCHADD is a very rare condition where a person is missing a certain protein and is unable to break down certain fats. This means they cannot produce enough energy and become ill. Without treatment babies can develop heart problems, go into a coma and it can cause death. Treatment involves changing the diet so it is low in particular types of fat. We found that there were uncertainties regarding the accuracy of the test and whether screening on day 5 would identify affected babies before symptoms begun. Also, more evidence is needed to know whether screening will lead to better long term outcomes. Find out more about our reviews here and here.

 Type 2 diabetes

Type 2 diabetes (T2DM) is a condition that causes a person’s blood sugar levels to be too high. In the short-term, people with diabetes might feel thirsty all the time, be very tired, and need to use the toilet a lot. In the long-term, diabetes can cause serious problems with the eyes, kidneys, nerves, and heart. Pre-diabetes (or non-diabetic hyperglycaemia) is the name given when a person has a higher than usual blood sugar level but they do not have diabetes. Warwick Screening undertook rapid reviews on the proportion of people with pre-diabetes who go on to develop T2DM; whether the current screening tests can predict who will have diabetes-related health problems in the future whether diet and exercise are useful treatments for pre-diabetes and whether randomised controlled trials have shown that screening for T2DM is beneficial. We found that Between 12 and 31% of people with pre-diabetes go on to develop diabetes over the short-to-medium term (3–10 years); extra health problems such as having high blood pressure, or a family history of diabetes might make it more likely to go from pre-diabetes to diabetes; people with higher blood glucose (especially in the diabetic range) might be at greater risk of health problems such as retinopathy than those with lower levels of blood glucose; people are less likely to develop diabetes if they take part in diet and exercise programmes and that screening for diabetes might not be helpful for people who have pre-diabetes. Find out more about our reviews here.

Professor Taylor-Phillips and the University of North Carolina have also undertaken a similar review of screening for prediabetes and diabetes along side the U.S. Preventive Services Task Force and the WHO. A copy of the evidence reviews can be found here and here.

Hereditary Haemochromatosis in Adults

Hereditary haemochromatosis is an inherited condition. It is caused by a faulty gene. It can lead to people to have too much iron in their body. This can put them at higher risk for problems with their heart, joints, and liver. Treatments to remove the extra iron from the body can lower a person’s chance of having health problems. Warwick Screening undertook rapid reviews to determine the health outcomes of people with hereditary haemochromatosis; whether people with health problems were more likely to have hereditary haemochromatosis; whether earlier treatment for hereditary haemochromatosis is better than later treatment and whether screening for hereditary haemochromatosis is helpful. We found that the chances of having raised iron in the body are higher for people who have the faulty gene than those who do not; the chances of having the faulty gene are higher in people with raised levels of iron in their body than those with normal levels of iron and that some people with hereditary haemochromatosis will have other health problems like extreme tiredness, liver cancer, and pneumonia, but most people will not. It was no clear if earlier treatment is better than later treatment and it is not known if screening would be helpful to people who have hereditary haemochromatosis. Find out more about our review here.