Tools for assessing quality and susceptibility to bias in observational studies in epidemiology: a systematic review and annotated bibliography.

BACKGROUND: Assessing quality and susceptibility to bias is essential when interpreting primary research and conducting systematic reviews and meta-analyses. Tools for assessing quality in clinical trials are well-described but much less attention has been given to similar tools for observational epidemiological studies. METHODS: Tools were identified from a search of three electronic databases, bibliographies and an Internet search using Google. Two reviewers extracted data using a pre-piloted extraction form and strict inclusion criteria. Tool content was evaluated for domains potentially related to bias and was informed by the STROBE guidelines for reporting observational epidemiological studies. RESULTS: A total of 86 tools were reviewed, comprising 41 simple checklists, 12 checklists with additional summary judgements and 33 scales. The number of items ranged from 3 to 36 (mean 13.7). One-third of tools were designed for single use in a specific review and one-third for critical appraisal. Half of the tools provided development details, although most were proposed for future use in other contexts. Most tools included items for selection methods (92%), measurement of study variables (86%), design-specific sources of bias (86%), control of confounding (78%) and use of statistics (78%); only 4% addressed conflict of interest. The distribution and weighting of domains across tools was variable and inconsistent. CONCLUSION: A number of useful assessment tools have been identified by this report. Tools should be rigorously developed, evidence-based, valid, reliable and easy to use. There is a need to agree on critical elements for assessing susceptibility to bias in observational epidemiology and to develop appropriate evaluation tools.

Impact of HIV-1 viral subtype on disease progression and response to antiretroviral therapy.

BACKGROUND: Our intention was to compare the rate of immunological progression prior to antiretroviral therapy (ART) and the virological response to ART in patients infected with subtype B and four non-B HIV-1 subtypes (A, C, D and the circulating recombinant form, CRF02-AG) in an ethnically diverse population of HIV-1-infected patients in south London. METHODS: A random sample of 861 HIV-1-infected patients attending HIV clinics at King's and St Thomas' hospitals' were subtyped using an in-house enzyme-linked immunoassay and env sequencing. Subtypes were compared on the rate of CD4 cell decline using a multi-level random effects model. Virological response to ART was compared using the time to virological suppression (< 400 copies/ml) and rate of virological rebound (> 400 copies/ml) following initial suppression. RESULTS: Complete subtype and epidemiological data were available for 679 patients, of whom 357 (52.6%) were white and 230 (33.9%) were black African. Subtype B (n = 394) accounted for the majority of infections, followed by subtypes C (n = 125), A (n = 84), D (n = 51) and CRF02-AG (n = 25). There were no significant differences in rate of CD4 cell decline, initial response to highly active antiretroviral therapy and subsequent rate of virological rebound for subtypes B, A, C and CRF02-AG. However, a statistically significant four-fold faster rate of CD4 decline (after adjustment for gender, ethnicity and baseline CD4 count) was observed for subtype D. In addition, subtype D infections showed a higher rate of virological rebound at six months (70%) compared with subtypes B (45%, p = 0.02), A (35%, p = 0.004) and C (34%, p = 0.01) CONCLUSIONS: This is the first study from an industrialized country to show a faster CD4 cell decline and higher rate of subsequent virological failure with subtype D infection. Further studies are needed to identify the molecular mechanisms responsible for the greater virulence of subtype D.

Evidence for onward transmission of HIV-1 non-B subtype strains in the United Kingdom.

An increasing proportion of new HIV diagnoses in the United Kingdom and other European countries are attributable to non-B subtype infections, mainly among black Africans with infections heterosexually acquired in sub-Saharan Africa. We examined whether there was evidence for onward transmission of non-B subtypes within an ethnically diverse HIV-1-infected cohort in South London. Three hundred eighty-four HIV-1-infected patients attending Kings College Hospital were subtyped using an in-house enzyme-linked immunoassay and env sequencing. Epidemiologic data were obtained from medical chart review and the patients' physician and were used to establish the most likely source and country of infection. Overall, 344 patients (154 black African, 148 white UK-born, and 42 black Caribbean) had an identifiable subtype. The prevalence of non-B subtypes among the black African, white, and black Caribbean patients was 96.8%, 14.2%, and 31%, respectively. Most non-B subtype infections were identified in black Africans (149 of 183 cases) and were mainly acquired in sub-Saharan Africa, but 22.9% (42 of 183 cases) of all non-B infections were probably acquired in the United Kingdom. Among the 21 white UK-born patients infected with a non-B subtype, 15 probably acquired the infection in the United Kingdom and only 6 of these patients reported a source sexual partner from an HIV endemic area. All 13 black Caribbean patients with a non-B infection most likely acquired their infection in the United Kingdom, most of whom (8 of 13 patients) were probably infected by a partner from an HIV endemic area. Potential acquisition of HIV infection in the United Kingdom was lowest among black African patients with a non-B infection, and most of these infections were probably acquired from a partner originating from an HIV endemic area. This study provides the first evidence for onward transmission of non-B subtypes in the United Kingdom, particularly among the black Caribbean population.

Surveillance of HIV-1 subtypes among heterosexuals in England and Wales, 1997-2000.

The molecular diversity and demographic characteristics among 976 anti-HIV-1-positive heterosexuals attending 15 sexually transmitted infection (STI) clinics participating in an unlinked anonymous HIV prevalence serosurvey in England and Wales during 1997-2000 were investigated. Subtypes were assigned by heteroduplex mobility assay or sequencing of the p17/p24 region of gag and the V3/V4 region of env and by sequencing of the protease gene. Overall, there was no significant change in the subtype distribution, with subtype C accounting for the majority (32%) of subtyped infections. Subtypes B (29%), A (12%), circulating recombinant forms (CRFs, 9%), unique recombinant forms (URFs, 8%), and subtypes D-H (8%) were also detected. Thirty-nine percent of infections in men were with subtype B, whereas subtype C was most common (38%) in women. Logistic regression analyses showed the relative risk (RR) of infection with a non-B subtype, compared with subtype B, to be greater in African-born individuals (RR = 28.9, P < 0.01), among newly diagnosed infections (RR = 3.4, P < 0.01), and in women (RR = 2.4, P < 0.01). These findings indicate a high level of genetic diversity among HIV-infected heterosexual STI clinic attendees in England and Wales. Recently, subtype C has become most prevalent, particularly in younger age groups, suggesting recent acquisition of this viral strain. The high proportion of non-B, CRF, and URF infections among UK-born individuals is consistent with mixing between migrants and UK-born individuals in England and Wales. As migration patterns change, continued monitoring of HIV genetic diversity will aid understanding of transmission patterns.