Cross-sectional study of medical advertisements in a national general medical journal: evidence, cost, and safe use of advertised versus comparative drugs.

BACKGROUND: Healthcare professionals are exposed to advertisements for prescription drugs in medical journals. Such advertisements may increase prescriptions of new drugs at the expense of older treatments even when they have no added benefits, are more harmful, and are more expensive. The publication of medical advertisements therefore raises ethical questions related to editorial integrity. METHODS: We conducted a descriptive cross-sectional study of all medical advertisements published in the Journal of the Danish Medical Association in 2015. Drugs advertised 6 times or more were compared with older comparators: (1) comparative evidence of added benefit; (2) Defined Daily Dose cost; (3) regulatory safety announcements; and (4) completed and ongoing post-marketing studies 3 years after advertising. RESULTS: We found 158 medical advertisements for 35 prescription drugs published in 24 issues during 2015, with a median of 7 advertisements per issue (range 0 to 11). Four drug groups and 5 single drugs were advertised 6 times or more, for a total of 10 indications, and we made 14 comparisons with older treatments. We found: (1) 'no added benefit' in 4 (29%) of 14 comparisons, 'uncertain benefits' in 7 (50%), and 'no evidence' in 3 (21%) comparisons. In no comparison did we find evidence of 'substantial added benefit' for the new drug; (2) advertised drugs were 2 to 196 times (median 6) more expensive per Defined Daily Dose; (3) 11 safety announcements for five advertised drugs were issued compared to one announcement for one comparator drug; (4) 20 post-marketing studies (7 completed, 13 ongoing) were requested for the advertised drugs versus 10 studies (4 completed, 6 ongoing) for the comparator drugs, and 7 studies (2 completed, 5 ongoing) assessed both an advertised and a comparator drug at 3 year follow-up. CONCLUSIONS AND RELEVANCE: In this cross-sectional study of medical advertisements published in the Journal of the Danish Medical Association during 2015, the most advertised drugs did not have documented substantial added benefits over older treatments, whereas they were substantially more expensive. From January 2021, the Journal of the Danish Medical Association no longer publishes medical advertisements.

Conflicts of interest in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews: associations with recommendations.

BACKGROUND: Treatment and diagnostic recommendations are often made in clinical guidelines, reports from advisory committee meetings, opinion pieces such as editorials, and narrative reviews. Quite often, the authors or members of advisory committees have industry ties or particular specialty interests which may impact on which interventions are recommended. Similarly, clinical guidelines and narrative reviews may be funded by industry sources resulting in conflicts of interest. OBJECTIVES: To investigate to what degree financial and non-financial conflicts of interest are associated with favourable recommendations in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews. SEARCH METHODS: We searched PubMed, Embase, and the Cochrane Methodology Register for studies published up to February 2020. We also searched reference lists of included studies, Web of Science for studies citing the included studies, and grey literature sources. SELECTION CRITERIA: We included studies comparing the association between conflicts of interest and favourable recommendations of drugs or devices (e.g. recommending a particular drug) in clinical guidelines, advisory committee reports, opinion pieces, or narrative reviews. DATA COLLECTION AND ANALYSIS: Two review authors independently included studies, extracted data, and assessed risk of bias. When a meta-analysis was considered meaningful to synthesise our findings, we used random-effects models to estimate risk ratios (RRs) with 95% confidence intervals (CIs), with RR > 1 indicating that documents (e.g. clinical guidelines) with conflicts of interest more often had favourable recommendations. We analysed associations for financial and non-financial conflicts of interest separately, and analysed the four types of documents both separately (pre-planned analyses) and combined (post hoc analysis). MAIN RESULTS: We included 21 studies analysing 106 clinical guidelines, 1809 advisory committee reports, 340 opinion pieces, and 497 narrative reviews. We received unpublished data from 11 studies; eight full data sets and three summary data sets. Fifteen studies had a risk of confounding, as they compared documents that may differ in other aspects than conflicts of interest (e.g. documents on different drugs used for different populations). The associations between financial conflicts of interest and favourable recommendations were: clinical guidelines, RR: 1.26, 95% CI: 0.93 to 1.69 (four studies of 86 clinical guidelines); advisory committee reports, RR: 1.20, 95% CI: 0.99 to 1.45 (four studies of 629 advisory committee reports); opinion pieces, RR: 2.62, 95% CI: 0.91 to 7.55 (four studies of 284 opinion pieces); and narrative reviews, RR: 1.20, 95% CI: 0.97 to 1.49 (four studies of 457 narrative reviews). An analysis combining all four document types supported these findings (RR: 1.26, 95% CI: 1.09 to 1.44). One study investigating specialty interests found that the association between including radiologist guideline authors and recommending routine breast cancer screening was RR: 2.10, 95% CI: 0.92 to 4.77 (12 clinical guidelines). AUTHORS' CONCLUSIONS: We interpret our findings to indicate that financial conflicts of interest are associated with favourable recommendations of drugs and devices in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews. However, we also stress risk of confounding in the included studies and the statistical imprecision of individual analyses of each document type. It is not certain whether non-financial conflicts of interest impact on recommendations.

The first ever Cochrane event in Russia and Russian speaking countries - Cochrane Russia Launch - Evidence-based medicine: Achievements and barriers (QiQUM 2015) International Conference, Kazan, December 7-8, 2015.

Kazan hosted Russia's second International Conference QiQUM 2015 on Cochrane evidence for health policy, which was entirely independent of the pharmaceutical or other health industry, bringing together 259 participants from 11 countries and 13 regions of the Russian Federation. The Conference was greeted and endorsed by world leaders in Evidence-based medicine, health and pharmaceutical information, policy and regulation, and the World Health Organization. Participants discussed the professional and social problems arising from biased health information, unethical pharmaceutical promotion, misleading reporting of clinical trials with consequent flaws in health care delivery and the role of Cochrane evidence for informed decisions and better health. The first in history Cochrane workshop, facilitated jointly by experts from Cochrane and the WHO, with 40 participants from Kazakhstan, Kyrgyzstan, Tajikistan and Russia introduced the concept of Cochrane systematic review and the Use of Cochrane evidence in WHO policy setting. Websites document conference materials and provide interface for future collaboration: http://kpfu.ru/biology-medicine/struktura-instituta/kafedry/kfikf/konferenciya/mezhdunarodnaya-konferenciya-39dokazatelnaya.html and http://russia.cochrane.org/news/international-conference.

Mammography screening. Benefits, harms, and informed choice.

The rationale for breast cancer screening with mammography is deceptively simple: catch it early and reduce mortality from the disease and the need for mastectomies. But breast cancer is a complex problem, and complex problems rarely have simple solutions. Breast screening brings forward the time of diagnosis only slightly compared to the lifetime of a tumour, and screen-detected tumours have a size where metastases are possible. A key question is if screening can prevent metastases, and if the screen-detected tumours are small enough to allow breast conserving surgery rather than mastectomy. A mortality reduction can never justify a medical intervention in its own right, but must be weighed against the harms. Overdiagnosis is the most important harm of breast screening, but has gained wider recognition only in recent years. Screening leads to the detection and treatment of breast cancers that would otherwise never have been detected because they grow very slowly or not at all and would not have been detected in the woman's lifetime in the absence of screening. Screening therefore turns women into cancer patients unnecessarily, with life-long physical and psychological harms. The debate about the justification of breast screening is therefore not a simple question of whether screening reduces breast cancer mortality. This dissertation quantifies the primary benefits and harms of screening mammography. Denmark has an unscreened "control group" because only two geographical regions offered screening over a long time-period, which is unique in an international context. This was used to study breast cancer mortality, overdiagnosis, and the use of mastectomies. Also, a systematic review of overdiagnosis in five other countries allowed us to show that about half of the screen-detected breast cancers are overdiagnosed. An effect on breast cancer mortality is doubtful in today's setting, and overdiagnosis causes an increase in the use of mastectomies. These findings are discussed in the context of tumour biology and stage at diagnosis. The information provided to women in invitations and on the Internet exaggerates benefits, participation is directly recommended, and the harms are downplayed or left out, despite agreement that the objective is informed choice. This raises an ethical discussion concerning autonomy versus paternalism, and the difficulty in weighing benefits against harms. Finally, financial, political, and professional conflicts of interest are discussed, as well as health economics.

General health checks in adults for reducing morbidity and mortality from disease.

BACKGROUND: General health checks are common elements of health care in some countries. These aim to detect disease and risk factors for disease with the purpose of reducing morbidity and mortality. Most of the commonly used screening tests offered in general health checks have been incompletely studied. Also, screening leads to increased use of diagnostic and therapeutic interventions, which can be harmful as well as beneficial. It is, therefore, important to assess whether general health checks do more good than harm. OBJECTIVES: We aimed to quantify the benefits and harms of general health checks with an emphasis on patient-relevant outcomes such as morbidity and mortality rather than on surrogate outcomes such as blood pressure and serum cholesterol levels. SEARCH METHODS: We searched The Cochrane Library, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Effective Practice and Organisation of Care (EPOC) Trials Register, MEDLINE, EMBASE, Healthstar, CINAHL, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) to July 2012. Two authors screened titles and abstracts, assessed papers for eligibility and read reference lists. One author used citation tracking (Web of Knowledge) and asked trialists about additional studies. SELECTION CRITERIA: We included randomised trials comparing health checks with no health checks in adults unselected for disease or risk factors. We did not include geriatric trials. We defined health checks as screening general populations for more than one disease or risk factor in more than one organ system. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the risk of bias in the trials. We contacted authors for additional outcomes or trial details when necessary. For mortality outcomes we analysed the results with random-effects model meta-analysis, and for other outcomes we did a qualitative synthesis as meta-analysis was not feasible. MAIN RESULTS: We included 16 trials, 14 of which had available outcome data (182,880 participants). Nine trials provided data on total mortality (155,899 participants, 11,940 deaths), median follow-up time nine years, giving a risk ratio of 0.99 (95% confidence interval (CI) 0.95 to 1.03). Eight trials provided data on cardiovascular mortality (152,435 participants, 4567 deaths), risk ratio 1.03 (95% CI 0.91 to 1.17) and eight trials on cancer mortality (139,290 participants, 3663 deaths), risk ratio 1.01 (95% CI 0.92 to 1.12). Subgroup and sensitivity analyses did not alter these findings.We did not find an effect on clinical events or other measures of morbidity but one trial found an increased occurrence of hypertension and hypercholesterolaemia with screening and one trial found an increased occurence of self-reported chronic disease. One trial found a 20% increase in the total number of new diagnoses per participant over six years compared to the control group. No trials compared the total number of prescriptions, but two out of four trials found an increased number of people using antihypertensive drugs. Two out of four trials found small beneficial effects on self-reported health, but this could be due to reporting bias as the trials were not blinded. We did not find an effect on admission to hospital, disability, worry, additional visits to the physician, or absence from work, but most of these outcomes were poorly studied. We did not find useful results on the number of referrals to specialists, the number of follow-up tests after positive screening results, or the amount of surgery. AUTHORS' CONCLUSIONS: General health checks did not reduce morbidity or mortality, neither overall nor for cardiovascular or cancer causes, although the number of new diagnoses was increased. Important harmful outcomes, such as the number of follow-up diagnostic procedures or short term psychological effects, were often not studied or reported and many trials had methodological problems. With the large number of participants and deaths included, the long follow-up periods used, and considering that cardiovascular and cancer mortality were not reduced, general health checks are unlikely to be beneficial.