Count the harms

Hippocrates may not have foreseen the complexities of modern medicine, but 24 centuries ago he (or whoever wrote the Hippocratic Oath) set down a fundamental rule for all clinicians and researchers—“first do no harm.” This rule has special resonance this week as we explore over-diagnosis in breast cancer screening, and the evolving clinical trial nightmare at Northwick Park.

Three weeks ago an editorial in the BMJ concluded that despite limitations, breast cancer screening does save lives (BMJ 2006;332: 499-500). But in the same issue of the journal we published an analysis by Karsten Juhl Jørgensen and Peter Gøtzsche of the letters inviting women for screening (BMJ 2006;332: 538-541). None of the letters mentioned the major harms of screening, and the authors concluded that organisers of screening programmes have a serious conflict of interest in wanting high uptake, which compromises their ability to provide balanced information about benefits and harms. That same week we also published “online first” Sophia Zackrisson and colleagues' 15 year follow-up from the Malmö trial of screening for breast cancer, which concluded that 10% of cancers detected by screening in women aged 55-69 are over-diagnosed.

This week we pull these strands together, along with letters selected from among the rapid responses to all three pieces (p 727). The total picture is far from reassuring. As Zackrisson et al explain (p 689), their 10% figure is a conservative estimate, since some of the women in the control group also had mammography. In a letter, Gilbert Welch and colleagues suggest that the more relevant figure is 24% since, based on the Malmö data, this is the chance that a screen detected cancer represents over-diagnosis (p 727). Their higher figure is more in line with Gøtzsche's estimate of 30% (p 727). Whatever the figure, or the reasons for it (pp 678, 691 and 727), there seems little doubt among our contributors that over-diagnosis is real and substantial. As Michael Baum relates, his unaddressed concerns about the UK's screening programme, which he helped to set up, led him to resign from the programme committee (p 728). He and Hazel Thornton (p 728) endorse Gøtzsche's concerns about conflicts of interest and the “fobbing off” of women with unbalanced, insufficient information.

Lack of proper information may prove to be at the heart of events that have left six young men seriously ill in hospital after the “first in man” trial of the monoclonal antibody TGN1412 (p 683). Michael Goodyear asks what lessons can be learned from this catastrophe (p 677), and Kate Mandeville describes her own experiences as a clinical trial volunteer (p 735). Questions are mounting about the trial, and they need answering. An inquiry by the UK's Medicines and Healthcare Products Regulatory Agency (MHRA) will not be enough, since this body may itself be implicated in mistakes that were made. There must be a full public inquiry if we are to prevent something like this happening again.