Screening Tests

Chapter 6

Screening Tests

Extra Problems

Supplementary to: Newman TB, Kohn MA. Evidence-based diagnosis. Cambridge ; New York: Cambridge University Press; 2009.

6. Andriole et al (1) reported the results of a randomized trial of prostate cancer screening with combination of prostate-specific antigen (PSA) testing and digital rectal examinations compared with usual care (which was whatever the physician usually did). After 7 years of follow-up the results of an "intention-to-treat" analysis" were as follows:

Diagnosis of Prostate Cancer / Death From Prostate Cancer / Total
Randomized To… / N / % / N / %
Annual Screening / 2820 / 7.35% / 50 / 0.130% / 38343
Usual Care / 2322 / 6.05% / 44 / 0.115% / 38350

There were significantly more patients diagnosed with prostate cancer in the group randomized to annual screening (116 vs. 95 per 10,000 person-years, risk ratio 1.21 95% CI 1.15 – 1.28). There were also more prostate cancer deaths in the group randomized to screening (2.0 vs. 1.7 per 10,000 person-years, risk ratio 1.14 95% CI 0.76 - 1.70).

In the following table, state whether the listed factor could explain why this study found that screening was WORSE than usual care in terms of cause-specific mortality. Briefly explain your answer.

Explains Finding That Screening is WORSE than Usual Care
Yes/No / Explain Answers
Volunteer Bias
Lead-Time Bias
Length Bias
Pseudodisease
Sticky Diagnosis Bias
Slippery Linkage Bias
Crossover Between Groups
Chance

7. Cervical Cancer Screening In India

In the developing world, cervical cancer death rates have not decreased the way they have in the developed world. A cluster-randomized trial in India showed that a one-time HPV screening program reduced cervical cancer death rates compared with usual care.(2) Simplified results are shown in the following table:

Offered HPV Screening / Control
N / 34126 / 31488
Avg Follow-up / 7.9 / 7.9
Cervical Cancers Diagnosed / 127 / 118
Cervical Cancer Deaths / 34 / 64
Cervical Cancer Death Rate/10,000 / 10.0 / 20.3 / P = 0.0006

a) Number Needed to Screen: How many women need to be offered HPV screening to prevent one cervical cancer death at 7.9 years of follow-up.

b) The above represents an “intention-to-treat” analysis. Roughly 80% of the women who were offered HPV screening received it and none of the control group received HPV screening. Would the true number needed to screen (vs. number needed to be offered screening) be higher or lower than the number calculated in part (a)?

Roughly the same number of cervical cancers were diagnosed in the group offered HPV screening and the control group (127 vs. 118). The table below shows the distribution of cancer diagnoses by stage at diagnosis.

Stage At Diagnosis / HPV Screening or Control? / HPV Screening or Control?
1A / 6% / 37%
1B / 22% / 26%
≥II / 69% / 31%
Unknown / 3% / 6%

c) Which column do you think represents which group? You have a 50/50 chance of labeling the columns correctly, but explain your choice.

d) In the following table, state whether the listed factor could explain why this study found that HPV screening REDUCED cervical cancer mortality. Briefly explain your answer.

Explains Finding That HPV Screening REDUCES deaths
Yes/No / Explain Answers
Volunteer Bias
Lead-Time Bias
Length Bias
Stage Migration Bias
Pseudodisease
Sticky Diagnosis Bias
Slippery Linkage Bias
Crossover Between Groups
Chance

8. Melanoma Screening

a. During the period from 1973 to 2001 the incidence of melanoma in children (0-19 years) increased by about 3% annually. Over that same period, overall 5-year survival increased by about 4% annually. (Strouse JJ et al. J Clin Oncol 2005;23:4735-41.) What do you think is the most likely explanation for this observation?.

b. Lewis reported trends in pediatric melanoma mortality in the US (Dematologic Surg 2008;34:152-59). From 1968 to 2004, (cause-specific) mortality from melanoma declined steadily, from about 3.5 per 10 million population to 1.5 per 10 million (a decrease averaging 2.3%/year). How does this observation fit with your answer to part A?

1. Andriole GL, Grubb RL, 3rd, Buys SS, Chia D, Church TR, Fouad MN, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009 Mar 26;360(13):1310-9.

2. Sankaranarayanan R, Nene BM, Shastri SS, Jayant K, Muwonge R, Budukh AM, et al. HPV screening for cervical cancer in rural India. N Engl J Med. 2009 Apr 2;360(14):1385-94.