Lee McCaffrey

A comparison of interview data and medical records for previous medical conditions and surgery

Although interview information is usually the sole source of data in case-control studies, the accuracy of such data is infrequently assessed. We compared interview data on selected medical conditions and surgical procedures with medical records of subjects with chronic lymphocytic leukemia. We examined agreement by type of respondent (self or surrogate), age, sex, race, and type of hospital. The strength of agreement between the two data sources (as measured by kappa statistics) was substantial kappa greater than 0.6) for splenectomy, appendectomy, asthma, and systemic lupus erythematosus; moderate kappa greater than 0.4) for tonsillectomy/adenoidectomy, tuberculosis, diverticulitis, hepatitis, rheumatic fever, and drug allergy; and poor kappa less than 0.3) for chronic bronchitis, chronic sinusitis, psoriasis, rheumatoid arthritis, and most other types of allergy. In general, self respondents had more accurate recall than surrogate respondents. Among self respondents the strength of agreement tended to be greater for males than females, for whites than blacks, and for subjects from referral hospitals than for community hospitals. No consistent patterns were apparent by age. Despite a number of limitations, the findings of the study provide an addition to the scant epidemiologic literature on this topic, and suggest that for certain conditions medical record data collection may be needed to supplement interview information.

Alzheimer's Disease Anti-inflammatory Prevention Trial: design, methods, and baseline results.

The Alzheimers Disease Anti‐inflammatory Prevention Trial (ADAPT) was designed to address whether non‐steroidal anti‐inflammatory drugs (NSAIDs) can prevent or delay the onset of Alzheimers disease (AD).

Association between Lifestyle Factors and CpG Island Methylation in a Cancer-Free Population

Background: Many risk factors have been associated with cancer, such as age, family history, race, smoking, high-fat diet, and poor nutrition. It is important to reveal the molecular changes related to risk factors that could facilitate early detection, prevention, and overall control of cancer. Methods: We selected six cancer-specific methylated genes that have previously been reported in primary tumors and have also been detected in different bodily fluids of cancer patients. Here, we used quantitative fluorogenic real-time methylation-specific PCR in plasma DNA samples for the detection of methylation changes from an asymptomatic population who do not have any known cancer. Results: The promoter methylation frequencies of the studied genes were as follows: APC (7%), CCND2 (22%), GSTP1 (2%), MGMT (9%), RARβ2 (29%), and P16 (3%). Promoter methylation of at least one of the genes analyzed was observed in ∼46% (72 of 157) of the samples by binary dichotomization. Promoter hypermethylation of at least two genes was detected in 17% (26 of 157) of the samples. RARβ2 methylation was observed in 45% of subjects who had a high-fat diet in contrast with those who had a low-fat diet (23%; P = 0.007). Discussion: Our findings may help to elucidate early methylation changes that may lead to cancer development. These methylation changes could be due to exposure to risk factors and may be useful for cancer prevention measures such as changes in lifestyle. Longitudinal follow-up of a high-risk population is needed to understand the association of methylation of candidate genes in cancer development. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2984–91)

The relationship of genital tract actinomycetes and the development of pelvic inflammatory disease

As a corollary to a case-control study evaluating the risk of pelvic inflammatory disease (PID) among users of an intrauterine contraceptive device (IUD), Papanicolaou smears were studied to detect the presence of actinomycetes. Forty-six PID case patients and 108 control patients were included in the corollary study. The presence of actinomycetes was noted only among current or past wearers of an IUD. Women with actinomycetes present on Papanicolaou smear had a 3.6-fold risk of hospitalization for PID, as compared to women without actinomycetes. This trend persisted when only IUD users were evaluated. Of patients with PID who had actinomycetes noted on the Papanicolaou smear, 87 1/2% had a tuboovarian abscess, compared to 28.9% of patients without actinomycetes. In addition, patients with actinomycetes present had PID treated surgically more frequently.

Cause-Specific Mortality Coding ☆: Methods in the Collaborative Ocular Melanoma Study COMS Report No. 14

Ascertainment of cause of death is often sought in clinical trials in which mortality is an outcome of interest. Standardized methods of coding all-cause and disease-specific mortality were developed and evaluated in the Collaborative Ocular Melanoma Study randomized trial of pre-enucleation radiation of large choroidal melanoma. All available clinical and pathologic materials documenting events prior to each reported death were reviewed systematically by a Mortality Coding Committee (MCC) to determine whether melanoma metastasis or local recurrence was present at the time of death. A level of certainty was assigned based on availability of local or central review of pathology materials. The outcome of the mortality coding protocol was evaluated both by assessing agreement between the judgment of the MCC and the presumed cause of death reported by the clinical center and, for a subset of patients, by assessing agreement between the MCC classification and the cause of death reported on the death certificate. As of July 31, 1997 (the cutoff date for the initial mortality report), 435 (95%) of 457 deceased patient files had been reviewed. The MCC classified 269 patients (62%) as dead with melanoma metastasis, 22 (5%) as dead with another malignant tumor, and 92 (21%) as dead with a malignant tumor of uncertain origin. Thirty-eight patients (9%) died with no evidence of malignancy; in 14 cases (3%), the presence or absence of malignancy could not be established due to lack of clinical information. Fair agreement (kappa = 0.34) was observed between the determinations of the MCC based on detailed review of materials and the cause of death reported on the death certificate, but death certificates alone underestimated the proportion of deaths due to metastatic choroidal melanoma. Detailed mortality coding identified difficulties associated with accurate reporting of cause-specific mortality in patients with choroidal melanoma.

Do we need to adjudicate major clinical events

Thanks to Granger and co-workers for their paper ‘Do we need to adjudicate major clinical events?’[1]. Their conclusion that ‘adjudication has not been shown to improve the ability to determine treatment effects’ is in accord with the views of many trialists. But views without data are easily dismissed. Experience in the Alzheimer’s Disease Antiinflammatory Prevention Trial (ADAPT) supports the authors’ conclusion. ADAPT was a multicenter, primary prevention, placebo-controlled, trial designed to determine whether selected NSAIDs (celecoxib and naproxen) administered long-term can prevent or delay onset of Alzheimer disease (AD) in a population of elderly people with a family history of AD-like dementia. Investigators in ADAPT suspended treatment in December 2004 because of concerns regarding the cardiovascular safety of the treatments relative to the prospect of the treatments preventing AD [2]. In making this decision, the investigators relied on raw, unadjudicated reports of events. It was surprisingly difficult to publish the results that underlay this decision. It took tries with five different journals before succeeding [3]. An oft cited concern of reviewers was the lack of an adjudication process for events reported. As it happened, the National Cancer Institute sponsored a study (the Cross Trial Safety Analysis – CTSA) in which CV events were harvested from 6 celecoxib-placebo controlled trials, (ADAPT among them) and centrally adjudicated [4]. There were no substantive qualitative differences in the adjudicated vs. raw results for ADAPT. The most notable difference was in the smaller number of events counted by ADAPT investigators. There can be no doubt that some central expertbased process for classifying events reduces noise in classification. However, because a decision to stop or alter a trial can arise from unanticipated adverse effects, it is typically impractical to establish and maintain ‘real time’ adjudication processes to inform such decisions. If trialists are expected to publish results as quickly as practical following decisions to stop or alter trials, then editors and reviewers should be prepared to accept manuscripts that describe the counts of adverse events that prompted such decisions, whether or not adjudicated.