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Screening Recommendations for Rare Newborn Diseases Often Made Without Systematic Reviews

NEW YORK (360Dx) – The vast majority of screening recommendations for rare diseases in newborns are made without a systematic review of available evidence, researchers in the UK reported on Wednesday.

In research described in The BMJ, researchers found that of 276 screening recommendations for 104 conditions, just 22 percent were based on systematic reviews of available evidence. They further found that such reviews were associated with a lower percentage of positive screening recommendations compared to when a review was not conducted, "suggesting that rigorous appraisal exposes the absence or unreliability of available evidence."

While many countries have in place "robust systems for reviewing new screening programmes," the researchers found that the steps were often ignored in the evaluation of whether rare diseases should be screened using the newborn blood spot test, they wrote. "Yet it remains essential to make evidence-based policy decisions because once screening programmes are started they are difficult to stop."

Globally, the number of conditions screened for using the newborn blood spot test range from five to 60 on screening panels, but it is unknown whether the decision to screen for conditions are based on country-specific disease prevalence, or healthcare systems and priorities, or whether they are determined by policies based on evidence review, in particular systematic reviews.

In their work, the researchers set out to analyze which conditions were screened for in different countries and whether systematic reviews were conducted in making those screening recommendations. They also sought to determine the association between recommendations — whether there was a positive or negative recommendation — and systematic reviews.

Searching through the websites of national policymaking organizations for documentation related to newborn blood spot testing, as well as other databases suggested by a panel of international experts on screening, they identified 134 policy documents. Of that, they excluded 41 documents for reasons such as the document not being from a national organization; the test being used was not a newborn blood spot test; duplication of included information; and others.

The authors then analyzed the remaining 93 reports covering 104 conditions from 14 countries including Australia; Belgium; Canada; Denmark; Finland; France; Germany; Italy; Japan; Netherlands; New Zealand; Spain; UK; and US.

A total of 276 recommendations were made in the reports, of which 159 (58 percent) were in favor of screening; 98 (36 percent) were against screening; and 19 made no suggestions either way.

Of those 276 recommendations, 60 included evidence from a systematic review.

The researchers noted that three key elements characterize the main benefits and harms of screening — test accuracy, benefits of early detection through screening, and overdiagnosis.

Of the 276 total recommendations, 115 (42 percent) did not consider test accuracy, 83 (30 percent) did not consider the benefits of early detection, and 211 (76 percent) did not consider overdiagnosis. Of the 60 recommendations that included systematic reviews, 21 of the reviews covered those three key elements, the authors wrote.

Notably, in the 60 decisions that included systematic reviews, 23 (38 percent) recommended screening, compared to 136 (63 percent) in the 216 decisions where no systematic reviews were conducted. Meanwhile 29 of 60 (48 percent) systematic reviewed decisions recommended not to screen, compared to 69 of the 216 (32 percent) decisions with no systematic reviews. No decision either way was made in eight of 60 decisions (13 percent) based on systematic reviews, compared to 11 of the 216 decisions (5 percent) with no systematic reviews.

Based on their results, the authors wrote, "We consider that quality appraisal in systematic reviewing serves as a mechanism to highlight bias in research studies (often biased away from the null). This might explain why expert policymaking groups that use systematic reviews are less likely to recommend testing."

They also tried to explain why systematic reviews aren't used more extensively to assess screening recommendation decisions and noted the lack of evidence from randomized controlled trials, "which is unavailable for most conditions included in newborn blood spot owing to their rarity."

They suggested that when policies are made regarding whether certain rare newborn diseases should be screened for, systematic reviews should be included in the policymaking process. While such reviews can be time-consuming and expensive, those issues can be addressed through international collaborations to conduct the reviews, they said.