Richard D T Farmer

University of Cape Town, Kaapstad, Western Cape, South Africa

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Publications (39)179.85 Total impact

  • CancerSpectrum Knowledge Environment 12/2013; · 14.07 Impact Factor
  • Journal of Family Planning and Reproductive Health Care 07/2013; 39(3):228-9. · 2.10 Impact Factor
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    ABSTRACT: BACKGROUND: Based principally on findings in three studies, the Collaborative Reanalysis (CR), the Women's Health Initiative (WHI), and the Million Women Study, it is claimed that hormone replacement therapy (HRT) is an established cause of breast cancer. The authors have previously reviewed those studies (Parts 1-4). The WHI findings were first published in 2002, following which the use of HRT rapidly declined. A correspondingly rapid decline in the incidence of breast cancer has been reported, and attributed to the drop in the use of HRT. The evidence, however, is conflicting. METHODS: Using generally accepted causal criteria, in this article (Part 5) the authors evaluate reported trends in the incidence of breast cancer. RESULTS: The evidence to suggest a correlated decline in the incidence of breast cancer following a decline in the use of HRT has not adequately satisfied the criteria of time order, detection bias, confounding, statistical stability and strength of association, internal consistency, and external consistency; biological plausibility is difficult to assess. CONCLUSIONS: Based on the observed trends in the incidence of breast cancer following the decline in HRT use, the ecological evidence is too limited either to support or refute the possibility that HRT causes breast cancer.
    Journal of Family Planning and Reproductive Health Care 04/2013; 39(2):80-88. · 2.10 Impact Factor
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    ABSTRACT: Based principally on findings in three studies, the collaborative reanalysis (CR), the Women's Health Initiative (WHI) and the Million Women Study (MWS), it is claimed that hormone replacement therapy (HRT) with estrogen plus progestogen (E+P) is now an established cause of breast cancer; the CR and MWS investigators claim that unopposed estrogen therapy (ET) also increases the risk, but to a lesser degree than does E+P. The authors have previously reviewed the findings in the CR and WHI (Parts 1-3). To evaluate the evidence for causality in the MWS. Using generally accepted causal criteria, in this article (Part 4) the authors evaluate the findings in the MWS for E+P and for ET. Despite the massive size of the MWS the findings for E+P and for ET did not adequately satisfy the criteria of time order, information bias, detection bias, confounding, statistical stability and strength of association, duration-response, internal consistency, external consistency or biological plausibility. Had detection bias resulted in the identification in women aged 50-55 years of 0.3 additional cases of breast cancer in ET users per 1000 per year, or 1.2 in E+P users, it would have nullified the apparent risks reported. HRT may or may not increase the risk of breast cancer, but the MWS did not establish that it does.
    Journal of Family Planning and Reproductive Health Care 01/2012; 38(2):102-9. · 2.10 Impact Factor
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    ABSTRACT: Based principally on findings in three studies, the Collaborative Reanalysis (CR), the Women's Health Initiative (WHI), and the Million Women Study (MWS), it is claimed that combined hormone replacement therapy (HRT) with estrogen plus progestogen is now an established cause of breast cancer. For unopposed estrogen therapy the evidence in the three studies is conflicting: the CR and MWS have reported increased risks in estrogen users, while the WHI has not. The authors have previously reviewed the findings in the CR (Part 1). To evaluate the evidence for causality in the WHI studies. Using generally accepted causal criteria, in this paper (Part 2) the authors evaluate the findings in the WHI for estrogen plus progestogen; in a related paper (Part 3) the authors evaluate the findings for unopposed estrogen. An evaluation of the MWS (Part 4), and of trends in breast cancer incidence following publication of the WHI findings in 2002 (Part 5) will follow. For estrogen plus progestogen the findings did not adequately satisfy the criteria of bias, confounding, statistical stability and strength of association, duration-response, internal consistency, external consistency or biological plausibility. HRT with estrogen plus progestogen may or may not increase the risk of breast cancer, but the WHI did not establish that it does.
    Journal of Family Planning and Reproductive Health Care 07/2011; 37(3):165-72. · 2.10 Impact Factor
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    ABSTRACT: Studies from the Women's Health Initiative have reported an increased risk of breast cancer in users of estrogen plus progestogen. Among users of estrogen alone an increased risk was not observed. To evaluate the evidence for unopposed estrogen. In a related article (Part 2) the authors apply generally accepted causal criteria to the findings for estrogen plus progestogen. Here (Part 3) the authors apply the criteria to the findings for unopposed estrogen, as reported in a clinical trial, and in combined data from the trial and an observational study. In the clinical trial, after 7.1 years of follow-up the relative risk (RR) of invasive breast cancer for women assigned to estrogen was 0.77 in an 'intention-to-treat' analysis (95% CI 0.59-1.01) and 0.67 (95% CI 0.47-0.97) in an 'as treated' analysis; after 10.7 years the risk reduction persisted. Time order was correctly specified; detection bias was minimal; in the 'as treated' analysis confounding was unlikely; duration-response and internal consistency could be evaluated only to a limited extent because of scanty data; the findings were discordant with increased risks observed in the Collaborative Reanalysis and the Million Women Study; biological plausibility could not be assessed. In the combined analysis, among women who had previously used estrogen soon after the menopause there was no clear evidence of either a reduction or an increase in the risk of breast cancer among women assigned to estrogen during the trial, or among women who were using estrogen in the observational study when follow-up commenced. The combined analysis did not satisfy the criteria of time order, bias, confounding, statistical stability and strength of association, duration-response, and internal consistency; biological plausibility could not be assessed. The evidence from the clinical trial suggests that unopposed estrogen does not increase the risk of breast cancer, and may even reduce it. The latter possibility, however, is based on statistically borderline evidence.
    Journal of Family Planning and Reproductive Health Care 06/2011; 37(4):225-30. · 2.10 Impact Factor
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    ABSTRACT: BACKGROUND Concern that hormone replacement therapy (HRT) may cause breast cancer has existed since the time it was introduced, and based on evidence in three studies, the Collaborative Reanalysis (CR), the Women's Health Initiative (WHI) and the Million Women Study (MWS), it is claimed that causality is now established. OBJECTIVE To evaluate the evidence for causality in the three studies. Methods Using generally accepted causal criteria, in this paper the authors begin with an evaluation of the CR. Analogous evaluations of the WHI and MWS will follow. RESULTS The findings in the CR did not adequately satisfy the criteria of time order, bias, confounding, statistical stability and strength of association, dose/duration-response, internal consistency, external consistency or biological plausibility. CONCLUSION HRT may or may not increase the risk of breast cancer, but the CR did not establish that it does.
    Journal of Family Planning and Reproductive Health Care 04/2011; 37(2):103-9. · 2.10 Impact Factor
  • Climacteric 08/2008; 11(4):267-72. · 1.96 Impact Factor
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    Arthritis & Rheumatology 03/2008; 59(2):297; author reply 297-8. · 7.48 Impact Factor
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    ABSTRACT: To evaluate the risk of venous thromboembolism (VTE) associated with the use of cyproterone acetate (CPA) amongst men with prostate cancer. Using data from the General Practice Research Database, cases of VTE were identified amongst men with prostate cancer. Four controls with no evidence of a VTE were selected for each case. The time from diagnosis of prostate cancer to first hormonal treatment, and from first hormonal treatment to VTE, was compared for different treatments. Adjusted risk estimates for VTE were derived from further analysis using a nested case-control study design amongst all men with advanced prostate cancer, qualified by evidence of hormonal treatment. The time between diagnosis and first treatment was significantly shorter for men first treated with CPA than for men first treated with a luteinizing hormone releasing hormone (LHRH) analogue (adjusted hazard ratio 1.33, 95% confidence interval, CI, 1.06-1.67). When the first treatment was CPA, the treatment-free period after diagnosis was significantly shorter for men who later had a VTE than for those who did not. The case-control study yielded an adjusted risk estimate for VTE amongst CPA users that was significantly higher than amongst men who were prescribed an LHRH analogue or who had had an orchidectomy (adjusted odds ratio 5.23, 95% CI 3.12-8.79). There was a greater risk of VTE associated with CPA, which might be due to differences in disease severity between users of different products. The clinical significance of this finding is unclear.
    BJU International 07/2007; 99(6):1398-403. · 3.05 Impact Factor
  • Richard Farmer
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    ABSTRACT: Epidemiological studies provide a valuable tool for the investigation of the causes of disease. However, such studies alone are rarely able to prove cause. No study is perfect and the evaluation of results must take account of the design and execution of the study together with the analytic methods used. Before imputing cause it is important to consider the findings against the criteria set out by Bradford Hill. Some of the problems with studies are discussed including the specification of the data collected, accuracy of information, end point definition, study size and the way results are presented. The issues are illustrated by reference to published papers. It is concluded that unless studies are evaluated and interpreted with care they may result in more harm than good.
    Maturitas 05/2007; 57(1):11-5. · 2.84 Impact Factor
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    A L Nightingale, R D T Farmer, C S de Vries
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    ABSTRACT: The purpose of this study was to calculate the prevalence of systemic lupus erythematosus (SLE) between 1992 and 1998 using the General Practice Research Database (GPRD) METHODS: We identified all individuals who had contributed at least 3 years of data to the GPRD and who had a diagnosis of SLE with supporting evidence of their diagnosis. We calculated the annual age- and sex-specific prevalence of SLE. Additionally, we stratified the prevalence by years of data contributed to the GRPD. In males the point estimate of the prevalence of SLE increased from 7.5/100,000 (CI(95) 6.3, 8.8) to 10.1/100,000 (CI(95) 7.8, 12.2) but this rise was not statistically significant. However, prevalence appeared to increase significantly amongst females from 42.6/100,000 (CI(95) 39.6, 45.6) in 1992 to 70.8/100,000 (CI(95) 65.1, 76.6) in 1998. This increase was mainly amongst women aged 50-79 and in those contributing more than 5 years of data and could not be explained by increasing incidence of SLE or decreasing mortality during the study period. We found an increasing prevalence of SLE that could not be explained by increasing incidence or decreasing mortality. This is almost certainly an artefact caused by the increased likelihood of detecting or confirming cases of chronic relapsing-remitting diseases with increasing time contributed to the GPRD.
    Pharmacoepidemiology and Drug Safety 03/2007; 16(2):144-51. · 2.90 Impact Factor
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    ABSTRACT: This paper profiles the usage and effectiveness of various LUTS/BPH drugs in real-life practice. The TRIUMPH study recorded the treatment and outcomes of 2351 newly-presenting LUTS/BPH patients in 6 European countries over a 1-year follow-up period. At each visit the clinician recorded the treatment, co-morbidities, complications and drugs prescribed, and the patient completed an IPSS questionnaire. The results were analysed using change in IPSS as the primary outcome measure. Over the study period 74.9% of patients were prescribed medication, the majority (83% of those medicated) were prescribed only a single drug. Tamsulosin was the most commonly prescribed drug in all countries (38% of medicated cases), although with national variation from 24% in Poland to 70% in Italy. The alpha-blockers were the most effective, with a mean reduction of 6.3 IPSS points. Finasteride was slightly less effective (4.1 points). Significant improvements were seen in 43% of patients on phytotherapy with Serenoa repens or Pygeum africanum compared to 57% of those on finasteride and 68% on alpha-blockers. The only combination therapy found to produce a statistically significant improvement over the use of individual drugs was finasteride+tamsulosin (8.1 points compared to 6.7 for tamsulosin alone and 4.2 for finasteride alone). All drug treatments showed some improvement over watchful-waiting for most patients over the study period: the alpha-blockers were found to be the most effective. There were marked national differences in prescribing patterns, both in individual drug choice and in the use of combination therapies.
    European Urology 02/2007; 51(1):207-15; discussion 215-6. · 10.48 Impact Factor
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    ABSTRACT: Knowledge of the clinical profile of the population with lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH) is important for health care management, impacting on manpower requirements, pharmacologic demands and health service costs. Data collected by the TransEuropean Research Into the Use of Management Policies for LUTS suggestive of BPH in Primary Health care project were used to profile 4979 patients from six European countries newly presenting with LUTS/BPH to general practitioners or office-based urologists. At recruitment, the clinician completed a questionnaire detailing the treatment provided, examination results, and covariates including age, initial symptom severity and comorbidities. The patient completed an International Prostate Symptom Score/quality-of-life questionnaire. The majority of patients (77%) sought medical advice because of the bothersomeness of their symptoms, and presented at ages between 58 and 71 years. Small but statistically significant differences among countries were found in initial symptom severity, initial quality of life and age at diagnosis, but these are not thought to be clinically significant. There were marked national differences in patient management, with, for example, 10% of patients in France reporting no examinations, compared with 0.5% in Poland, while free-flow measurements varied from less than 1% in France to 35% in Poland. Patient heterogeneity does not explain the differences in patient management among countries, which undoubtedly is the result of differences in health care traditions, infrastructure and socioeconomic factors, as well as patient preference.
    European Urology 10/2006; 50(3):555-61; discussion 562. · 10.48 Impact Factor
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    ABSTRACT: To determine the age- and sex-specific incidence rates of systemic lupus erythematosus (SLE) in the population of the General Practice Research Database (GPRD) between 1.1.1992 and 31.12.1998. We searched the GPRD for incident cases of clinically diagnosed SLE with supporting evidence of diagnosis in their medical record. Cases must have had at least 3 years of data in their record prior to date of first diagnosis. We calculated the annual and age- and sex-specific incidence rates of SLE. We identified 390 incident cases of SLE yielding an incidence rate (IR) of 3.02/100 000/year (CI(95) 2.72, 3.32). There were 41 males (IR 0.65/100 000/year (CI(95) 0.45, 0.85)) and 349 females (IR 5.30/100 000/year (CI(95) 4.75, 5.86)). The median age at diagnosis for males and females was 54 and 46 years, respectively, and the peak incidence rates were amongst women aged 30-69 years. The incidence rate ratio for females to males was 8.15 (CI(95) 5.9, 11.6). This is the first UK-wide study of the incidence of SLE. The results of this study are consistent with previous smaller studies conducted in Nottingham and Birmingham. Although recording of symptoms of SLE is not complete in the GPRD, we conclude that incident cases can be successfully identified because generally there is supporting evidence of diagnosis in medical record.
    Pharmacoepidemiology and Drug Safety 10/2006; 15(9):656-61. · 2.90 Impact Factor
  • C S de Vries, S E Bromley, R D T Farmer
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    ABSTRACT: To establish the risk of myocardial infarction (MI) in users of hormone replacement therapy (HRT) compared with non-users and to compare the risk between different HRT regimens. A population-based cohort and case-control study, and a case-control study nested within a cohort of HRT users, using the UK General Practice Research Database. Differences between HRT regimen, mode of administration and duration and recency of use were examined whilst adjusting for confounding. In the cohort and case-control study, 4537 cases of MI were identified in 2.62 million observed women years, cases were age-matched to 27,220 controls. In both studies, current and past HRT use were associated with reduced risk estimates for MI compared with no prior use. MIs were less likely to be fatal amongst women who had used HRT than amongst never users (OR(adj) 0.58; 95% CI 0.45-0.75). No difference in risk was seen between current and past use, oral and transdermal HRT or between different regimens (p>0.44). In the nested study, no difference was found in the association with MI risk between different oestrogen-progestogen combinations or between different combinations and tibolone. Unopposed oestrogen use was not associated with a decrease in risk compared with combined HRT. These results are consistent with previous observational studies in supporting the hypothesis that use of postmenopausal HRT is associated with a decrease in risk of acute myocardial infarction (AMI). Case fatality differed between HRT users and non-users, suggesting a protective effect of HRT. This study does not demonstrate a difference between regimens.
    Maturitas 02/2006; 53(3):343-50. · 2.84 Impact Factor
  • John Logie, Gary M Clifford, Richard D T Farmer
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    ABSTRACT: To describe the incidence, prevalence and management of lower urinary tract symptoms (LUTS), suggestive of benign prostatic hyperplasia, reported in UK general practice. All clinical information relating to LUTS and its treatment was assessed for men aged > or = 45 years and registered on the UK General Practice Research Database (GPRD) at some time between 1992 and 2001. Incidence and prevalence were derived from the GPRD population. Secular trends in the management of LUTS were examined from prescribing rates and the intervals between first symptoms, first treatment and surgery or catheterization. The incidence of reported LUTS showed a strong linear increase with age. The prevalence increased from 3.5% for men aged 45-49 years to > 30% for men aged > 85 years. Between 1992 and 2000 there was a five-fold increase in the proportion of time with LUTS when men were receiving medical treatment. This was accompanied by a progressive decrease in the intervals between first symptoms and first drug treatment, and a significant increase in the intervals from first symptoms or first treatment to surgery or catheterization. Treated men received surgery or catheterization significantly later than those receiving no drug treatment. There has been a significant increase in the use of medical therapy for LUTS over the last decade. The accompanying postponement of surgery/catheterization is likely to be a result, at least in part, of successful earlier medical treatment and the treatment of a greater proportion of symptomatic men.
    BJU International 04/2005; 95(4):557-62. · 3.05 Impact Factor
  • Gary M Clifford, John Logie, Richard D T Farmer
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    ABSTRACT: To compare the risk of liver injury in men treated with alpha1-blockers against that in a similar non-exposed population. Using a study population registered on the UK General Practice Research Database (GPRD) we performed (a) a retrospective cohort analysis amongst men with lower urinary tract symptoms (LUTS) indicative of benign prostatic hypertrophy (BPH) comparing the incidence of liver injury in men exposed to alpha1-blockers with the incidence in those not exposed, and (b) two nested case-control studies looking at risk factors associated with the development of liver injury compared with age- or practice-matched controls. Amongst 45,851 men with LUTS/BPH, 9666 were exposed to an alpha1-blocker and 154 were identified with drug-induced/idiopathic liver injury. The crude incidence of liver injury in men with LUTS/BPH exposed to an alpha1-blocker was not statistically significantly different from that in the unexposed population (13.9 vs. 11.0 cases per 10,000 exposed years: incidence rate ratio (IRR) 1.28 [95% confidence interval (CI): 0.64, 2.31]). In the case-control analyses, the adjusted odds ratio (OR) of liver injury associated with exposure to alpha1-blockers compared with no use was not statistically significant (age-matched OR 0.92 [95%CI: 0.43, 1.97]; practice-matched OR 0.98 [95%CI: 0.45, 2.16]). Our analyses confirmed an association between liver injury and alcohol consumption as well as exposure to various classes of drugs known to be potentially hepatotoxic. This study could not offer any evidence to support an association between exposure to alpha1-blockers and liver injury in men with LUTS/BPH.
    Pharmacoepidemiology and Drug Safety 03/2005; 14(2):75-80. · 2.90 Impact Factor
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    ABSTRACT: Many animal studies and studies on intermediate clinical endpoints have shown hormone replacement therapy (HRT) to be associated with both favourable and unfavourable cardiovascular effects. We reviewed the literature regarding HRT and the distinct endpoint of acute myocardial infarction (AMI) in peri- and postmenopausal women. Searches of the MEDLINE and EMBASE databases were conducted. Fifty papers were identified as eligible for inclusion: eight randomised controlled trials, 18 cohort studies, 23 case-control studies and one case-control and cohort study. The single large primary prevention randomised controlled trial on HRT and the risk of AMI in generally healthy women (Women's Health Initiative trial) reported a small yet significantly increased risk of AMI in postmenopausal women receiving combined HRT. This contrasts with a large number of observational studies that suggested a protective effect, although in many of these studies the results were not statistically significant. Inconclusive evidence on the effect of duration of use does not support the notion that a possible protective association is causal. Detection bias and residual confounding are alternative explanations for the associations observed in the randomised controlled trial and observational studies. No studies on groups of women with existing cardiovascular disease or with diabetes mellitus, including the only large secondary prevention trial (Heart and Estrogen/Progestin Replacement Study), reported a significant change in AMI risk between HRT users and non-users. There is insufficient evidence to suggest that HRT is associated with a change in the risk of AMI in the majority of women. However, certain subgroups of women with specific genetic polymorphisms may be more susceptible to a change in the risk of AMI with HRT use.
    Drug Safety 02/2005; 28(6):473-93. · 2.62 Impact Factor
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    ABSTRACT: Case series and spontaneous reports of endometrial cancer have raised the question as to whether the use of tibolone (introduced into the UK in 1991) is associated with an increased risk of endometrial cancer. This study set out to evaluate whether tibolone use is associated with an increased risk of endometrial cancer. Age-adjusted incidence rate ratios (IRRs) of endometrial cancer were calculated for tibolone use compared with the use of other hormone replacement therapy (HRT). Separate sets of controls, matched for age and general practice, were compared with cases, all nested within a cohort of HRT users identified from the UK General Practice Research Database (GPRD). Conditional logistic regression analysis, adjusted for potential confounders, was used to study the association between tibolone use and the risk of endometrial cancer. 4995 women used tibolone as their first HRT product; 10 783 (4.3%) of the users of combined HRT had changed to tibolone at some time during the study period. Amongst women whose HRT began with tibolone, the age-adjusted IRR relative to those who started with combined sequential HRT was 1.83 (95% CI 1.19, 2.82). The nested case-control study comprised 162 cases, each matched to two sets of 972 controls. There were 43 tibolone-exposed subjects, 28 of whom had used other HRT before or after tibolone. The adjusted odds ratio of the risk of endometrial cancer in women who had ever used tibolone, compared with users of combined sequential HRT, was 1.54 (95% CI 1.03, 2.32) in the age-matched set and 1.58 (95% CI 1.01, 2.47) in the practice-matched set. Sensitivity analyses did not decrease the risk estimates found. Tibolone may be associated with an increased risk of endometrial cancer compared with conventional forms of HRT, but our data are fragile. Residual bias and uncontrolled confounding cannot be excluded, and follow-up time is insufficient to draw any firm conclusions with respect to the endometrial safety of tibolone.
    Drug Safety 02/2005; 28(3):241-9. · 2.62 Impact Factor