{'fraction_non_alphanumeric': 0.0162666137671097, 'fraction_numerical': 0.006943066851815116, 'mean_word_length': 5.2789539227895395, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Troubles with trials

Current thinking about the interpretation of screening tests suggests that the likelihood ratio, which measures the relationship between sensitivity and specificity, is the best indicator of the usefulness of a test, such that if the likelihood ratio is more than ten, we have found a ‘good test’. One weakness of the likelihood ratio is that it does not depend on the prevalence of the disorder, unlike the positive and negative values of the test; thus with conditions of low prevalence it is possible that a screening test may have a high likelihood ratio but a low positive predictive value, rendering the test useless if the false positives cause many unnecessary invasive interventions. In clinical practice most screening tests are relatively inefficient, and are useful more for the exclusion rather than the diagnosis of disease, in which case the negative predictive value becomes the most important attribute of the test. Three papers in this issue illustrate the value of the negative predictive value. Pelvic lymphadenectomy is an important part of the surgical treatment of many gynaecological cancers, but has two main problems surgical complications may occur such as haemorrhage and the formation of lymphocysts; and histological examination of the pelvic lymph nodes often reveals no metastases. Hanna-Leena Helin and her colleagues (pages 4 1 0 4 14) developed a technique of ultrasonic examination of the pelvic and para-aortic lymph nodes during surgery just before formal lymphadenectomy, and calculated the efficiency of the technique in the diagnosis of metastases to the lymph nodes. The test has only modest sensitivity and specificity, but the predictive value of a negative test was 97%. This finding is of great practical importance, for it should give gynaecologists courage not to undertake a hazardous lymphadenectomy where the ultrasound scan is negative. Helin and her colleagues are now developing the technique for use in the laparoscopic treatment of gynaecological cancer. Abnormal bleeding in women taking hormone replacement therapy is common and causes anxiety for the woman and her gynaecologist. The usual investigation is some form of endometrial biopsy, but R. Lindgren and colleagues (pages 421-426) show that this is not always necessary. The authors conducted an observational study of 564 women taking various forms of hormone replacement therapy who underwent transvaginal ultrasound examination and endometrial biopsy, to determine the efficiency of ultrasound in the identification of significant endometrial pathology. All the women took combined oestrogen and progestogen hormone replacement therapy, in short cycle, long cycle or continuous combined regimens; and before the study none had significant gynaecological disorders. After two years of treatment no case of endometrial cancer or atypical hyperplasia was found, and only eight cases of simple hyperplasia. The sensitivity and specificity of endometrial thickness of 4 mm or more measured by transvaginal ultrasound were only modest, but the predictive value of a negative test was 99%; however, about one-half of all the women had positive tests. This information is still useful, for it will reduce the need for endometrial biopsy by one half in women taking hormone replacement therapy who have abnormal vaginal bleeding. What is the appropriate treatment for small ovarian cysts fortuitously discovered in perimenopausal women? If the cyst persists or enlarges it is usually removed, but in only a few cases is significant pathology present. H. Sasaki and colleagues (pages 415-420) found 225 women with asymptomatic small ovarian cysts in a study of screening for ovarian cancer, and followed these women for over six years. Cox’s proportional hazards model showed that the only factors which were associated with persistence or progression of the cysts were the concentrations in the plasma of carcinoembryonic antigen and CA19-9 at the initial diagnosis. The authors did not formally measure the efficiency of these tests, but inspection of Table 3 shows that they have modest sensitivity and specificity, and that the predictive value of a negative test is about 80%. This is not quite so convincing as ultrasonography in the diagnosis of lymph node metastases or endometrial hyperplasia, but a more sophisticated analysis of small ovarian cysts is required, where the output of the Cox’s proportional hazards model is used to construct a score, the predictive value of which is then tested, using a receiver-operator characteristic curve. The score developed in this way may help prevent unnecessary operations. Because of the limitations in our understanding of the biology of gynaecological cancer our screening tests are crude, and one penalty of this inherent inefficiency is an excess of invasive treatments. These three papers show the value of tests with a high negative predictive value, to prevent unnecessary lymphadenectomy, unnecessary endometrial biopsy and unnecessary oophorectomy.