OBJECTIVES: To consider methods and related evidence for evaluating bias in non-randomised intervention studies. DATA SOURCES: Systematic reviews and methodological papers were identified from a search of electronic databases; handsearches of key medical journals and contact with experts working in the field. New empirical studies were conducted using data from two large randomised clinical trials. METHODS: Three systematic reviews and new empirical investigations were conducted. The reviews considered, in regard to non-randomised studies, (1) the existing evidence of bias, (2) the content of quality assessment tools, (3) the ways that study quality has been assessed and addressed. (4) The empirical investigations were conducted generating non-randomised studies from two large, multicentre randomised controlled trials (RCTs) and selectively resampling trial participants according to allocated treatment, centre and period. RESULTS: In the systematic reviews, eight studies compared results of randomised and non-randomised studies across multiple interventions using meta-epidemiological techniques. A total of 194 tools were identified that could be or had been used to assess non-randomised studies. Sixty tools covered at least five of six pre-specified internal validity domains. Fourteen tools covered three of four core items of particular importance for non-randomised studies. Six tools were thought suitable for use in systematic reviews. Of 511 systematic reviews that included non-randomised studies, only 169 (33%) assessed study quality. Sixty-nine reviews investigated the impact of quality on study results in a quantitative manner. The new empirical studies estimated the bias associated with non-random allocation and found that the bias could lead to consistent over- or underestimations of treatment effects, also the bias increased variation in results for both historical and concurrent controls, owing to haphazard differences in case-mix between groups. The biases were large enough to lead studies falsely to conclude significant findings of benefit or harm. Four strategies for case-mix adjustment were evaluated: none adequately adjusted for bias in historically and concurrently controlled studies. Logistic regression on average increased bias. Propensity score methods performed better, but were not satisfactory in most situations. Detailed investigation revealed that adequate adjustment can only be achieved in the unrealistic situation when selection depends on a single factor. CONCLUSIONS: Results of non-randomised studies sometimes, but not always, differ from results of randomised studies of the same intervention. Non-randomised studies may still give seriously misleading results when treated and control groups appear similar in key prognostic factors. Standard methods of case-mix adjustment do not guarantee removal of bias. Residual confounding may be high even when good prognostic data are available, and in some situations adjusted results may appear more biased than unadjusted results. Although many quality assessment tools exist and have been used for appraising non-randomised studies, most omit key quality domains. Healthcare policies based upon non-randomised studies or systematic reviews of non-randomised studies may need re-evaluation if the uncertainty in the true evidence base was not fully appreciated when policies were made. The inability of case-mix adjustment methods to compensate for selection bias and our inability to identify non-randomised studies that are free of selection bias indicate that non-randomised studies should only be undertaken when RCTs are infeasible or unethical. Recommendations for further research include: applying the resampling methodology in other clinical areas to ascertain whether the biases described are typical; developing or refining existing quality assessment tools for non-randomised studies; investigating how quality assessments of non-randomised studies can be incorporated into reviews and the implications of individual quality features for interpretation of a review's results; examination of the reasons for the apparent failure of case-mix adjustment methods; and further evaluation of the role of the propensity score.

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Evaluating non-randomised intervention studies.

Prostate specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate.

This article summarizes evidence and issues associated with psychological assessment. Data from more than 125 meta-analyses on test validity and 800 samples examining multimethod assessment suggest 4 general conclusions: (a) Psychological test validity is strong and compelling, (b) psychological test validity is comparable to medical test validity, (c) distinct assessment methods provide unique sources of information, and (d) clinicians who rely exclusively on interviews are prone to incomplete understandings. Following principles for optimal nomothetic research, the authors suggest that a multimethod assessment battery provides a structured means for skilled clinicians to maximize the validity of individualized assessments. Future investigations should move beyond an examination of test scales to focus more on the role of psychologists who use tests as helpful tools to furnish patients and referral sources with professional consultation.

Psychological Testing and Psychological Assessment: A Review of Evidence and Issues.

AGA technical review on nonalcoholic fatty liver disease

This Opinion of the EFSA Panel on Dietetic Products, Nutrition, and Allergies (NDA) deals with the setting of Dietary Reference Values (DRVs) for fats. A lower bound of the reference intake range for total fat of 20 energy % (E%) and an upper bound of 35 E% are proposed. Fat intake in infants can gradually be reduced from 40 E% in the 6 12 month period to 35–40 E% in the 2nd and 3rd year of life. For specific fatty acids the following is proposed: saturated fatty acid (SFA) and trans fatty acid intake should be as low as possible; not to set any DRV for cis-monounsaturated fatty acids; not to formulate a DRV for the intake of total cis-polyunsaturated fatty acids (PUFA); not to set specific values for the n-3/n-6 ratio; to set an Adequate Intake (AI) of 4 E% for linolenic acid; not to set any DRV for arachidonic acid; not to set an UL for total or any of the n 6 PUFA; to set an AI for alpha-linilenic acid (ALA) of 0.5 E% not to set an UL for ALA; to set an AI of 250 mg for eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) for adults; to set an AI of 100 mg DHA for infants (>6 months) and young children <24 months; to increase by 100 200 mg preformed DHA in addition to the AI for adults as an adequate supply of n-3 long chain PUFA during pregnancy and lactation; not to set any DRV for conjugated linoleic acid. For cholesterol it was decided not to propose a reference value beside the limitation on the intake of SFA.

https://orbit.dtu.dk/files/6355881/prod11324452634179.Scientific.pdf

Scientific Opinion on Dietary Reference Values for fats, including saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids, and cholesterol

Plasma lipid and lipoprotein responses to dietary fat and cholesterol: a meta-analysis.

Alcohol, athletics, and fraternities have been targeted in the popular media as primary causes of sexual aggression on campus. Except in the case of alcohol, the empirical data supporting these associations is weak. The present study assessed the joint contribution of these three variables to the prediction of sexual aggression among a sample of 530 undergraduate men including 140 athletes representing all varsity sports. Approximately 11% of the variance in the level of sexual aggression was accounted for by four variables including self-reported intensity of alcohol use and degree of athletic participation, but not fraternity affiliation. The alcohol and athletic variables also discriminated those men who reported participating in gang rapes ( N = 17) from those not involved. Although significant prediction was achieved, the results must be viewed cautiously as the power of the effects was small. The article concludes with the implications of the findings for rape prevention education.

The Prediction of Sexual Aggression by Alcohol Use, Athletic Participation, and Fraternity Affiliation

Prostate-specific antigen (PSA) is a sensitive and specific serum marker for monitoring disease activity in men with prostatic carcinoma. Despite reports of elevation of levels of this analyte in men with benign prostatic hyperplasia, no information is available correlating the serum levels with the actual prostatic abnormalities in men having prostatectomy for presumed benign disease. In the present investigation, the authors compared pre-operative serum PSA levels with prostate disease in 81 men with bladder outlet obstruction. Five pathologic groups were found: incidental high-grade carcinoma (n = 3), low-grade carcinoma (n = 11), acute inflammation (n = 16) with or without chronic inflammation, Prostatic intraepithelial neoplasia (PIN) (n = 25), and benign hyperplasia (n = 26). Serum PSA levels were significantly elevated in both low- and high-grade carcinoma, acute inflammation, and PIN when compared with the patients with benign hyperplasia with and without chronic inflammation. Within the four groups with elevated levels, use of PSA levels could separate only the high-grade cancer patients who were subsequently shown to have metastatic disease. Only one patient with simple hyperplasia had PSA levels in the abnormal range.

Serum Prostate-Specific Antigen and Prostate Pathology in Men Having Simple Prostatectomy

An in vitro study sought to determine the feasibility of using computed tomography (CT) to analyze the chemical composition of renal calculi and thus aid in selecting the best treatment method. Sixty-three coded calculi were scanned in a water bath. Region-of-interest measurements provided the mean, standard deviation, and minimum and maximum pixel values for each stone. These parameters were correlated with aspects of the stones' chemical composition. A multivariate analysis showed that the mean and standard deviation of the stones' pixel values were the best CT parameters for differentiating types of renal calculi. By using computerized mapping techniques, uric acid calculi could be perfectly differentiated from struvite and calcium oxalate calculi. The latter two types also were differentiable, but to a lesser extent. CT has a potential role as an adjunct to clinical and laboratory methods for determining the chemical composition of renal calculi in an effort to select optimal treatment.

John A. Gaines

Papers

Plasma lipid and lipoprotein responses to dietary fat and cholesterol: a meta-analysis.

The Prediction of Sexual Aggression by Alcohol Use, Athletic Participation, and Fraternity Affiliation

Serum Prostate-Specific Antigen and Prostate Pathology in Men Having Simple Prostatectomy

Computed tomographic analysis of renal calculi.

Exercise Testing Three Weeks after Myocardial Infarction