Tuesday, November 18

Bradford Hill Causation Criteria- Revisited

Bersempena exam saya yang bakal menjelma, saya terbitkan sebuah tulisan sains yang pernah dihantar sahabat saya, saudara Nubli di dalam sebuah Yahoo Groups kira-kira setahun yang lalu.

Selamat membaca, dan kepada Firdaus, selamat menghadapi exam walaupun batuk tak surut lagi.

Bradford Hill Causation Criteria- Revisited

Association and causation are two different things in epidemiological studies. It is important for medico to appreciate the differences between those two.

Let’s say, today I publish a cohort study entitled “Strawberry can cause amnesia” (I made up this thing, for the sake of example). I found that there is a positive correlation between strawberry and amnesia. Everything is perfect: sample size is big enough, statistical calculation is significant, all major confounding factors have been eliminated etc.At the end of the day I can’t state “Strawberry is a causal factor of amnesia” but “Strawberry is associated to amnesia” unless if I can fulfil Bradford Hill Causation Criteria.In the 1960s, the epidemiologist Austin Bradford Hill proposed a set of criteria which would allow epidemiologists to judge whether an association was likely to be causal.

I will use smoking as a causal factor of lung cancer to explain Bradford Hill Causation Criteria.

1. Strength of association– The risk of people who smoked 15-24 cigarettes a day are 26 times more likely to die from lung cancer than lifelong non-smokers (1)

2. Biologic gradient– The more cigarettes smoked, the greater the risk of cancer(2)

3. Consistency-It has been observed in different types of study, in different study populations (2, 3)

4. Specificity– Don’t over-emphasize the importance of the characteristic – smoking causes several cancers. One of the most notorious is- smoking causes lung cancer (2,4,5)

5. TemporalityLung cancer occurs a long time after smoking is initiated (6)

6. Plausibility– Cigarette is known to contain carcinogens (7,8)

7. Reversibility– Quitting smoking reduces the risk of cancer (9,10,11)

8. IndependenceThe association stands independent of confounding variables, such as class, sex, race, occupation;

As smoking fulfills all Bradford Hill causation criteria, we can make conclusion that smoking is a causal factor of lung cancer and not merely associated to lung cancer.The biggest problem to even associate MMR with autism is there is no temporal relationship between those two.Core and atypical autism cases under 60 months of age and fitted trends by year of birth 1979–92 (12)MMR was introduced in the UK in 1988. But we can see from the graph above there was no trend change of prevalence of autism since 1988. The graph shows steady exponential increase from 1979 to 1987 and keeps the same trend until the end of the study (1992). The increase of autism cases were there, even before MMR was introduced, and keep increasing at the same exponential trend even after MMR had been introduced in 1988. Increase of autism cases are independent of MMR vaccination.Unless new study shows otherwise, we shouldn’t stop vaccination program just because someone or some group of people think so.

Adapted from Vaccination Tutorial, Week 2, Semester 2, Year 2, Queen’s Belfast.
Conveyed by Dr William Moore at Mulhouse Building, Royal Victoria Hospital, Belfast, on 6/2/2008.

Reference:1. Doll, R. and A. Hill, Smoking and carcinoma of the lung; preliminary report. Br Med J, 1950. 2: p. 739-482. IARC, IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Tobacco smoke and involuntary smoking. Vol. 83. 2004, Lyon: IARCPress.3. Peto, R., et al., Mortality from smoking in developed countries 1950-2000: Indirect estimates from National Vital Statistics. 1994, Oxford: OUP4. Doll, R. and R. Peto, Epidemiology of Cancer. Oxford Textbook of Medicine, ed. D. Warrell, et al. 2003, Oxford: OUP5. Sasco, A., M. Secretan, and K. Straif, Tobacco smoking and cancer: a brief review of the epidemiological evidence. Lung Cancer, 2004. 45: p. S3-S9.6. http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/E/Epidemiology.html7. Hoffman, D. and I. Hoffman, The changing cigarette: Chemical studies and bioassays., in Risks Associated with Smoking Cigarettes with Low Machine-Measured Yields of Tar and Nicotine (Smoking and Tobacco Control Monograph No. 13). 2001, NCI: Bethseda. p. 159-1918. Pfeifer, G., et al., Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers. Oncogene, 2002. 21: p. 7435-519. Doll, R., et al., Mortality in relation to smoking: 50 years' observations on male British doctors. BMJ, 2004. 328: p. 151910. Wakai, K., et al., Decrease in risk of lung cancer death in Japanese men after smoking cessation by age at quitting: Pooled analysis of three large-scale cohort studies. Cancer Sci, 2007. 98(4): p. 584-589.11. US DHHS. The Health Benefits of Smoking Cessation: A report of the Surgeon General. 199012. Taylor et al. Lancet, 1998;353:2026-9

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