Why Core GRADE is needed: introduction to a new series in The BMJ

Dear Editor

In my view, the GRADE system faces two principal concerns. First, while GRADE is designed to assess the certainty of evidence, it is often applied inappropriately—used to lend credibility to flawed clinical studies rather than to rigorously evaluate the quality of randomised controlled trials (RCTs) and the suitability of their designs and endpoints. This misuse can legitimise studies that lack methodological rigour.

Second, although GRADE is intended to facilitate the transition from evidence to guideline development, this step is not always necessary. The aim of Evidence-Based Medicine (EBM) is to integrate clinical expertise with patient values, guided by the best available evidence. Clinical decisions does not necessarily require strict adherence to guidelines or evidence. While clinicians and patients routinely discuss the potential benefits and risks of interventions, the final decision ultimately lies with the patient. Guidelines are designed to support clinical decision-making—not to dictate a universal standard of care. Their primary role is to consolidate expert knowledge to aid individual practitioners, rather than to impose population-wide mandates.

Breast cancer screening provides a relevant example. Although GRADE is not formally applied to breast cancer screening, the challenges of evaluating evidence and developing guidelines are common. The natural history of screen-detected breast cancer remains poorly understood, and studies evaluating screening, diagnosis, and treatment often lack appropriate control groups. As a result, many such trials function more as observational case series than as rigorously controlled experiments. Among the approximately ten RCTs assessing screening, all incorporate diagnostic and treatment phases within the screening arm, rendering them randomised but effectively uncontrolled. The absence of well-designed RCTs undermines the reliability of systematic reviews and meta-analyses in this area. Nevertheless, the US Preventive Services Task Force (USPSTF) has assigned a Grade B recommendation for breast cancer screening, suggesting that benefits outweigh harms. This grading is due to the fact that the harms of breast surgery are almost exclusively psychological. However, they should still clearly outweigh the uncertain benefits.

In such cases, a Grade I (Insufficient) rating would be more appropriate, reflecting the current uncertainty around benefit. Patients should be clearly informed of the possibility of no benefit prior to giving consent, in accordance with the Declaration of Helsinki. Study designs must be scientifically robust and include valid control groups; otherwise, they risk generating uninterpretable data and may lead to the misallocation of healthcare resources, along with serious ethical and economic consequences.

When trial designs or endpoints are even slightly inadequate, guidelines should prioritize the need for more rigorous trials rather than justify existing limitations. The GRADE approach should also be reoriented to reflect this priority.

REFERENCE

Zahl PH, Gøtzsche PC, Mæhlen J. Natural history of breast cancers detected in the Swedish mammography screening programme: a cohort study. Lancet Oncol. 2011 Nov;12(12):1118-24. doi: 10.1016/S1470-2045(11)70250-9.

US Preventive Services Task Force; Nicholson WK, Silverstein M, Wong JB, et al. Screening for Breast Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2024 Jun 11;331(22):1918-1930. doi: 10.1001/jama.2024.5534