Quantification of harms in cancer screening trials: literature review | BMJ

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Results Out of 4590 articles assessed, 198 (57 trials, 10 screening technologies) matched the inclusion criteria. False positive findings were quantified in two of 57 trials (4%, 95% confidence interval 0% to 12%), overdiagnosis in four (7%, 2% to 18%), negative psychosocial consequences in five (9%, 3% to 20%), somatic complications in 11 (19%, 10% to 32%), use of invasive follow-up procedures in 27 (47%, 34% to 61%), all cause mortality in 34 (60%, 46% to 72%), and withdrawals because of adverse effects in one trial (2%, 0% to 11%). The median percentage of space in the results section that reported harms was 12% (interquartile range 2-19%).

Conclusions Cancer screening trials seldom quantify the harms of screening. Of the 57 cancer screening trials examined, the most important harms of screening—overdiagnosis and false positive findings—were quantified in only 7% and 4%, respectively.

Introduction

Cancer screening can lead to harm as well as benefit.1 2 3 Harm related to screening can be somatic or psychosocial.4 5 6 7 8 9 10 11 12 13 Harms result from the screening test itself, from investigations because of false positive findings, and from overdiagnosis with subsequent overtreatment.3 5 12 13 Given the potential for serious harms in healthy individuals, screening should be offered only when the benefits are firmly documented and considered to outweigh the harms, which should be equally well quantified. The determination of benefit from screening requires assessment in randomised clinical trials, which are also capable of providing high quality evidence on harms.14 15 In general, however, harms are poorly reported in randomised trials,16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 and there is some evidence that reporting of harms is worse in non-pharmacological trials than in trials assessing drugs.22 23 24

At least three additional arguments support the importance of reporting harms in randomised trials of cancer screening. Firstly, screening is offered to healthy individuals and is an intervention initiated by the healthcare system, not at the request from a patient to solve a health problem. Secondly, interventions for which the benefits are modest or uncertain merit detailed consideration of harms,32 and systematic reviews of randomised trials of screening have shown either modest33 34 35 or no36 reductions in cancer specific mortality. Thirdly, a benefit for some will come at the expense of harm to others.37 38 39

The minimum evidence required to assess the harms of screening includes the frequencies of false positive findings, overdiagnosis, and complications of diagnostic investigations and treatment.13 In addition, withdrawals because of harms19 and the use of invasive follow-up procedures can be considered as proxy measures of severe harms. We hypothesised that cancer screening trials would not consistently or sufficiently quantify the expected associated harms.

Methods

Eligibility criteria

We included trials that evaluated breast cancer screening with mammography, self examination, or clinical examination; colorectal cancer screening with sigmoidoscopy or colonoscopy, faecal occult blood testing, or virtual colonoscopy; liver cancer screening with ultrasonography, α fetoprotein, or a combination; lung cancer screening with chest radiography or low dose spiral computed tomography of chest; ovarian cancer screening with ultrasonography, serological markers, or a combination; oral cancer screening with visual inspection; prostate cancer screening with prostate specific antigen, digital rectal examination, or a combination; and testicular cancer screening with self examination or clinical examination.

Publications reporting randomised trials were eligible if the trial compared a group of participants undergoing a cancer screening intervention with either no screening or an alternative screening intervention....