Inclusion of Older People Reflective of Real-World Clinical Practice in Cardiovascular Drug Trials.

Background Underrepresentation of older people in clinical trials remains. This study aimed to examine the inclusion of older people and associated safety and efficacy reports from clinical trials of new molecular entities for cardiovascular disease indications since commencement of the US Food and Drug Administration Drug Trial Snapshot (DTS) Program. The DTS provides concise information on participants included in clinical trials supporting US Food and Drug Administration approval of new drugs. Methods and Results A cross-sectional analysis between January 1, 2015 and April 30, 2019 of DTS data including approval date, indication, number of trials and participants, age distribution, efficacy, and safety statements was conducted. Participation-to-prevalence ratio (PPR) was used to describe representation of older participants in trials relative to disease population. Efficacy and safety statements regarding age were compared with drug prescribing information. A total of 72 079 participants from 10 DTS reports were identified and 39 625 (55.0%) were aged ≥65 years old. Overall, 63.6% of cardiovascular disease DTS reports were representative of people aged ≥65 years old for specific cardiovascular disease conditions. Underrepresentation was observed in 4 DTS: 2 for heart failure (PPR 0.48 and 0.62), 1 for pulmonary arterial hypertension (PPR 0.72), and 1 for venous thromboembolism (PPR 0.38). Participants in clinical trials for new drugs for the treatment of atrial fibrillation (PPR 0.99 and 1.21) and hypercholesterolemia (PPR 0.84 and 0.97) were reflective of the older population for these diseases. An increased risk of adverse events in older participants was reported in 40% DTS safety statements but no differences were reported in the drug product information. Conclusions Despite the fact that >60% of cardiovascular disease trial participants for new molecular entities included in the DTS program were representative of the older population in real-world clinical practice, concerns remain for conditions including heart failure or venous thromboembolism. Drug product information safety statements regarding age differences in adverse events were not reflective of trial findings. An increased directive is needed to facilitate the generation of real-world evidence and appropriate reporting within drug product information for these potentially at-risk patient populations.

Comorbidities in Australian women with hormone-dependent breast cancer: a population-based analysis.

OBJECTIVE: To compare how frequently selected chronic diseases developed in women with breast cancer receiving endocrine therapy, and in women without cancer. DESIGN, SETTING AND PARTICIPANTS: Retrospective, rolling cohort study, analysing a random 10% sample of Pharmaceutical Benefits Scheme (PBS) data for the period 1 January 2003 - 31 December 2014. Women with breast cancer who first commenced endocrine therapy between January 2004 and December 2011 were identified, and age- and sex-matched (1:10) by comorbidity with control groups of women who did not have a dispensing record for antineoplastic agents during the study period or the comorbidity of interest at baseline. MAIN OUTCOME MEASURES: Development of any of eight pre-selected comorbidities, identified in PBS claims data with the RxRisk-V model. RESULTS: Women with hormone-dependent breast cancer were significantly more likely than women in the control group to develop depression (overall hazard ratio [HR], 1.36; 95% CI, 1.26-1.46), pain or pain-inflammation (HR, 1.30; 95% CI, 1.23-1.38), osteoporosis (overall HR, 1.27; 95% CI, 1.17-1.39), diabetes (HR, 1.24; 95% CI, 1.10-1.41), cardiovascular disorders (overall HR, 1.22; 95% CI, 1.13-1.32), and gastric acid disorders (HR, 1.20; 95% CI, 1.13-1.28). The hazard ratios for developing cardiovascular disorders, depression and osteoporosis were highest during the first year of endocrine therapy. The risk of hyperlipidaemia was lower among women with breast cancer than in the control group (HR, 0.88; 95% CI, 0.81-0.96). There was no significant difference between the two groups in the risk of reactive airway diseases (HR, 1.05; 95% CI, 0.98-1.13). CONCLUSION: Comorbid conditions are more likely to develop in women who have been diagnosed with hormone-dependent breast cancer than in women without cancer. Our results further support the need to develop appropriate models of care to manage the multiple chronic disorders of breast cancer survivors.

Influence of medication risks and benefits on treatment preferences in older patients with multimorbidity.

Multimorbidity is associated with use of multiple medicines, increased risk of adverse events and treatment conflicts. This study aimed to examine how older patients with multimorbidity and clinicians balance the benefits and harms associated with a medication and in the presence of competing health outcomes. Interviews were conducted with 15 participants aged ≥65 years with 2 or more chronic conditions. Three clinical scenarios were presented to understand patient preference to take a medicine according to i) degree of benefit, ii) type of adverse event and impact on daily living and iii) influence of comorbid conditions as competing health outcomes. Semi-structured interviews were also conducted with participants (n=15) and clinicians (n=5) to understand patient preferences and treatment decisions, in the setting of multimorbidity. The median age of participants was 79 years, 55% had 5 or more conditions and 47% took 8 or more medicines daily. When the level of benefit of the medicine ranged from 14% to 70%, 80% of participants chose to take the medicine, but when adverse effects were present, this was reduced to 0-33% depending upon impact on daily activities. In the presence of competing health outcomes, 13%-26% of patients chose to take the medicine. Two-thirds of patients reported that their doctor respects and considers their preferences and discussed medication benefits and harms. Interviews with clinicians showed that their overall approach to treatment decision-making for older individuals with multimorbidity was based upon 2 main factors, the patients' prognosis and their preferences. The degree of benefit gained was not the driver of patients' preference to take a medicine; rather, this decision was influenced by type and severity of adverse effects. Inclusion of patient preferences in the setting of risks and benefits of medicines with consideration and prioritization of competing health outcomes may result in improved health outcomes for people with multimorbidity.

Ten years of publicly funded biological disease-modifying antirheumatic drugs in Australia.

Biological disease-modifying antirheumatic drugs (bDMARDs) for rheumatoid arthritis (RA) treatment were among the first high-cost medicines to be subsidised in Australia. High-cost medicines pose several challenges to the Australian National Medicines Policy, which aims to provide timely access to effective medicines at a cost individuals and the community can afford. Thus, novel restriction criteria were developed to encourage cost-effective use of bDMARDs. Government expenditure on bDMARD subsidies for RA treatment grew to about $383 million in 2014. Evidence that initiation and continuation criteria for bDMARDs meet usually applied cost-benefit criteria is lacking. The combined expenditure on tocilizumab, certolizumab pegol and golimumab (added to the Australian Government's Pharmaceutical Benefits Scheme in 2010) was $93 million in 2014, which is 210% over the initial estimate. Present and future challenges with regard to bDMARDs for RA and other high-cost drugs include improved expenditure predictions, monitoring of cost-effectiveness in relation to actual use and strategic development, regulation and use of biosimilars. Ten years of documentation on clinical and laboratory findings indicating eligibility to initiate and continue on bDMARDs remains un-used. These data represent an untapped opportunity to promote quality of use of bDMARDs and biosimilars and to improve cost predictions for high-cost drugs.

Analgesic Use and Daytime Sleepiness in Residents With and Without Dementia in Residential Aged Care Facilities.

BACKGROUND: Managing pain in residents of residential aged care facilities (RACFs) is challenging, especially for people with dementia. Clinicians must weigh the benefits of analgesic use against the potential for adverse events, particularly daytime sleepiness. OBJECTIVES: The aim was to investigate the association between analgesic use and daytime sleepiness in residents with and without dementia in RACFs. METHODS: This was a cross-sectional study of 383 permanent residents from six low-level and high-level RACFs in South Australia. Main measures included analgesic use in the previous 24 h, analgesic load and self-reported daytime sleepiness. Covariates included relevant comorbidities (insomnia, depression, painful conditions), Charlson's Comorbidity Index, sedative load, self-reported and clinician-observed pain and dementia severity. Logistic regression was used to compute odds ratios (ORs) and confidence intervals (CIs) for the association between analgesic use and daytime sleepiness. RESULTS: Analgesics were used by 288 residents (75.2%) in the previous 24 h. These included paracetamol (n = 264, 68.9%), opioids (n = 110, 28.7%) and oral NSAIDs (n = 14, 3.7%). Overall, 116 (30.3%) residents were categorized as having daytime sleepiness. Of those with dementia, 77 (45.6%) were categorized as having daytime sleepiness. Opioid use in the previous 24 h was not associated with daytime sleepiness in unadjusted or adjusted analyses. Paracetamol use was positively associated with daytime sleepiness (OR 2.31; 95% CI 1.20-4.42). CONCLUSION: Although daytime sleepiness occurred in a large number of residents, especially those with dementia, this sleepiness was not necessarily associated with use of opioids. The risk of opioid-induced sedation may have been managed by strategies including preferential prescribing of paracetamol to residents at risk of sleepiness, opioid discontinuation in residents who experienced sleepiness, and use of low doses of opioids.

Discounting of medicines in Australian community pharmacies.

OBJECTIVE: There are many medicines listed on the Australian Pharmaceutical Benefits Scheme (PBS) in which point of sale price is less than the level of the general patient co-payment. In these circumstances, the patient covers the total cost of the medicine from their own pocket with no government subsidy. The aim of the present study was to compare the consumer prices of under general co-payment prescription medicines between banner group pharmacies with open discounting policies and community pharmacies without; and to assess the impact of the April 2012 PBS price disclosure policies on the discounts offered. METHODS: The consumer prices of 31 under co-payment medicines were collected from banner group pharmacy websites and individual pharmacies both before and after April 2012. PBS maximum prices were obtained from the PBS website. Absolute and relative price differences between PBS and pharmacy groups were calculated. RESULTS: Before April 2012, banner group pharmacies provided discounts to patients of around 40% per prescription, whereas other pharmacies provided discounts of around 15%. Total price savings were on average $9 per prescription at banner group pharmacies and $3.50 at other pharmacies. Percentage discounts did not change greatly after April 2012, when price decreases occurred on the PBS. CONCLUSIONS: Banner group pharmacies with pricing strategies are able to provide greater discounts to patients compared with other pharmacies. Community pharmacies still have the ability to provide substantial discounts after the April 2012 price reductions. WHAT IS KNOWN ABOUT THE TOPIC?: There is currently little known about the under co-payment medicines market in Australia and the price discounts available to patients. WHAT DOES THIS PAPER ADD?: This research shows that patients who purchase under co-payment medicines are able to save money if they purchase from pharmacies with openly advertised discounting policies. Price reductions related to the implementation of the price disclosure policy had a small effect on the discounts offered by community pharmacies to patients. WHAT ARE THE IMPACTS FOR PRACTITIONERS?: The effect of discounting on under co-payment medicines to patients may increase their ability to afford essential medicines. Questions remain on whether the effect of discounting on under co-payment medicines may affect the quality of professional services provided to patients by pharmacists.

Analgesic use, pain and daytime sedation in people with and without dementia in aged care facilities: a cross-sectional, multisite, epidemiological study protocol.

INTRODUCTION: People living with dementia may experience and express pain in different ways to people without dementia. People with dementia are typically prescribed fewer analgesics than people without dementia indicating a potential difference in how pain is identified and treated in these populations. The objectives of this study are to (1) investigate the prevalence of analgesic load, pain and daytime sedation in people with and without dementia in Australian residential aged care facilities (RACFs), and (2) investigate the clinical and diagnostic associations between analgesic load, pain and daytime sedation in people with and without dementia in Australian RACFs. METHODS/ANALYSIS: This will be a cross-sectional study of 300 permanent residents of up to 10 low-level and high-level RACFs in South Australia with and without dementia. Trained study nurses will administer validated and dementia-specific assessments of self-reported and clinician-observed pain, sedation and other clinical and humanistic outcomes. Medicine-use data will be extracted directly from each resident's medication administration chart. Binary and multinominal logistic regression will be used to compute unadjusted and adjusted ORs and 95% CIs for factors associated with pain, analgesic load and daytime sedation. These factors will include dementia severity, behavioural and psychological symptoms, quality of life, resident satisfaction, attitudes towards medicines, activities of daily living and nutritional status. ETHICS AND DISSEMINATION: Institutional ethics approval has been granted. The findings will be disseminated through public lectures, professional and scientific conferences and in peer-reviewed journal articles. The findings of this study will allow for a better understanding of the prevalence and factors associated with analgesic use, pain and other outcomes in residential care. The findings of this study will be used to inform the development and implementation of strategies to improve the quality of life of people with dementia.

Comorbid diabetes and COPD: impact of corticosteroid use on diabetes complications.

OBJECTIVE: To identify if there is a dose-dependent risk of diabetes complications in patients treated with corticosteroids who have both diabetes and chronic obstructive pulmonary disorder (COPD). RESEARCH DESIGN AND METHODS: A retrospective study of administrative claims data from the Australian Government Department of Veterans' Affairs, from 1 July 2001 to 30 June 2008, of diabetes patients newly initiated on metformin or sulfonylurea. COPD was identified by dispensings of tiotropium or ipratropium in the 6 months preceding study entry. Total corticosteroid use (inhaled and systemic) in the 12 months after study entry was determined. The outcome was time to hospitalization for a diabetes-related complication. Competing risks and Cox proportional hazard regression analyses were conducted with adjustment for a number of covariates. RESULTS: A total of 18,226 subjects with diabetes were identified, of which 5.9% had COPD. Of those with COPD, 67.2% were dispensed corticosteroids in the 12 months from study entry. Stratification by dose of corticosteroids demonstrated a 94% increased likelihood of hospitalization for a diabetes complication for those who received a total defined daily dose (DDD) of corticosteroids≥0.83/day (subhazard ratio 1.94 [95% CI 1.14-3.28], P=0.014), by comparison with those who did not receive a corticosteroid. Lower doses of corticosteroid (<0.83 DDD/day) were not associated with an increased risk of diabetes-related hospitalization. CONCLUSIONS: In patients with diabetes and COPD, an increased risk of diabetes-related hospitalizations was only evident with use of high doses of corticosteroids. This highlights the need for constant revision of corticosteroid dose in those with diabetes and COPD, to ensure that the minimally effective dose is used, together with review of appropriate response to therapy.

Does antidepressant medication use affect persistence with diabetes medicines?

PURPOSE: This study aimed to examine the effect of antidepressant use on persistence with newly initiated oral antidiabetic medicines in older people. METHODS: A retrospective study of administrative claims data from the Australian Government Department of Veterans' Affairs, from 1 July 2000 to 30 June 2008 of new users of oral antidiabetic medicines (metformin or sulfonylurea). Antidepressant medicine use was determined in the 6 months preceding the index date of the first dispensing of an oral antidiabetic medicine. The outcome was time to discontinuation of diabetes therapy in those with antidepressant use compared with those without. Competing risks regression analyses were conducted with adjustment for covariates. RESULTS: A total of 29,710 new users of metformin or sulfonylurea were identified, with 7171 (24.2%) dispensed an antidepressant. Median duration of oral antidiabetic medicines was 1.81 years (95% CI 1.72­1.94) for those who received an antidepressant at the time of diabetes medicine initiation, by comparison to 3.23 years (95% CI 3.10­3.40) for those who did not receive an antidepressant. Competing risk analyses showed a 42% increased likelihood of discontinuation of diabetes medications in persons who received an antidepressant (subdistribution hazard ratio 1.42, 95% CI 1.37­1.47, p < 0.001). CONCLUSIONS: The results of this large population-based study demonstrate that depression may be contributing to non-compliance with medicines for diabetes and highlight the need to provide additional services to support appropriate medicine use in those initiating diabetes medicines with co-morbid depression.

Assessment of the therapeutic value of new medicines marketed in Australia.

BACKGROUND: The belief that all new medicines bring a therapeutic innovation and better health outcomes is widely shared among the public, health professionals and policy makers. OBJECTIVES: To examine the therapeutic value of new medicines marketed in Australia using two classification systems. METHODS: The therapeutic value of new medicines was categorised using the Motola's s and the Ahlqvist-Rastad's systems for all approvals made by the Australian Therapeutics Goods Administration (TGA) between 2005 and 2007. Scores were assigned independently by the three authors on the basis of the Public Summary Documents and Prescrire' review articles. RESULTS: Overall, 217 approval recommendations were made including 81 (37.3%) for new indications and 69 (31.8%) for new medicines. In Motola's rating system, 31 (52.5%) of the 59 drugs were rated as pharmacological or technological innovations and 28 (47.5%) were rated as therapeutic innovations. Only seven of the 59 drugs (11.9%) were rated as important innovations. In Ahlqvist-Rastad's system, only a third of the new drugs were rated as "added therapeutic value". CONCLUSION: Only a minority of the new medicines marketed in Australia provide added therapeutic value compared to existing treatments. Stricter regulatory approval criteria would ensure better safety of the public and simplify the reimbursement processes.

Chronic disease management: does the disease affect likelihood of care planning?

OBJECTIVE: To compare the demographic, socioeconomic, and medical characteristics of patients who had a General Practitioner Management Plan (GPMP) with those for patients without GPMP. METHODS: Cohort study of patients with chronic diseases during the time period 1 July 2006 to 30 June 2008 using the Australian Department of Veterans' Affairs (DVA) claims database. RESULTS: Of the 88 128 veterans with chronic diseases included in the study, 23 015 (26%) veterans had a GPMP and 11 089 (13%) had a Team Care Arrangement (TCA). Those with a GPMP had a higher number of comorbidities (P<0.001), and a higher use of services such as health assessment and medicine review (P<0.001) than did those without GPMP. Diabetes was associated with a significantly increased use of GPMP compared with all other chronic diseases except heart failure. CONCLUSIONS: GPMPs are used in a minority of patients with chronic diseases. Use is highest in people with diabetes.

Major bleeding risk associated with warfarin and co-medications in the elderly population.

PURPOSE: Warfarin management in the elderly population is complex as medicines prescribed for concomitant diseases may further increase the risk of major bleeding associated with warfarin use. We aimed to quantify the excess risk of bleeding-related hospitalisation when warfarin was co-dispensed with potentially interacting medicines. METHODS: A retrospective cohort study was undertaken over a 4-year period from July 2002 to June 2006 to examine bleeding risk associated with medications co-administered in patients taking warfarin using an administrative claims database from the Australian Department of Veterans' Affairs. All veterans aged 65 years and over who were new users of warfarin were followed until death or study end. Risk of bleeding was assessed using a Poisson GEE model adjusting for age, gender, socioeconomic status, co-morbidity index, previous bleeding related hospitalisations and indicators of health service use. RESULTS: Overall, 17661 veterans who used warfarin at any time during the study period were included. The overall incidence rate of bleeding-related hospitalisations was 4.1 (95% CI 3.7-4.6) per 100 person-years in veterans who were not receiving potentially interacting medicines. Bleeding-related hospitalisation rates were significantly increased when warfarin was co-prescribed with low-dose aspirin (Adjusted rate ratio (AdjRR) 1.44, 95% CI 1.00-2.07), clopidogrel (AdjRR 2.23, 95% CI 1.48­3.36), clopidogrel with aspirin (AdjRR 3.44, 95% CI 1.28-9.23), amiodarone (AdjRR 3.33, 95% CI 1.38­8.00) and antibiotics (AdjRR 2.34, 95% CI 1.55-3.54). CONCLUSIONS: Models assessing bleeding risk with warfarin should take account of the range of potentially harmful medicine combinations used in elderly people with comorbid conditions.

Ageing well: improving the management of patients with multiple chronic health problems.

AIM: To identify and evaluate the management and care of older people with multiple chronic health problems (MCHP). METHODS: Administrative health data from the Department of Veterans' Affairs and bio-social data from the Australian Longitudinal Study of Ageing are used to determine prevalence of MCHP, treatment patterns and patient outcomes. Focus groups and semistructured interviews are used to gain patient and health practitioner perspectives. RESULTS: The prevalence of MCHP in older people is high (65%) and is associated with increased use of health services, mortality and poorer self-rated health. Australian disease-specific guidelines fail to address MCHP, and treatment conflicts with the potential to cause harm, were common. CONCLUSION: Improvements in the care and management of older people with MCHP requires: a multifaceted approach, across the health-care system; better coordination of holistic, patient-centred multidisciplinary care; and effective communication and education of all stakeholders. The Health reform agenda in Australia provides an opportunity for change.

Co-morbidity and potential treatment conflicts in elderly heart failure patients: a retrospective, cross-sectional study of administrative claims data.

BACKGROUND: Co-morbidity of both cardiac and non-cardiac conditions is common in the elderly with heart failure (HF) and can be associated with adverse clinical outcomes. OBJECTIVES: The aims of this study were to examine the prevalence of co-morbidity and potential treatment conflicts that may result in adverse clinical outcomes in a large cohort of elderly HF patients. METHODS: We conducted a cross-sectional study using administrative claims data (1 April to 31 July 2007) from the Department of Veterans' Affairs, Australia, on all veterans aged ≥65 years with HF. Co-morbidities were defined using the pharmaceutical based co-morbidity index Rx-Risk-V. Potential treatment conflicts for patients with HF and co-morbid diseases were identified from Australian clinical guidelines or reference compendia and their prevalence in the data were determined. RESULTS: A total of 6730 patients were included in the study, with a median of 6 co-morbid conditions (interquartile range [IQR] 4-7) and 11 (IQR 8-15) unique medicines. Almost the entire HF cohort (97.8%) were identified as having at least one co-morbid condition that may cause a potential treatment conflict, with 55% having three or more. The conditions identified as being of greatest concern, based on their prevalence and potential for treatment conflict, were chronic airways disease, depression, chronic pain/inflammatory disease, glaucoma, diabetes mellitus and diseases treatable with corticosteroids. CONCLUSIONS: Potential treatment conflicts are common in the highly co-morbid population of elderly patients with HF, and may influence the therapeutic management of not only HF but all conditions present.

Medicines information provided by pharmaceutical representatives: a comparative study in Australia and Malaysia.

BACKGROUND: Pharmaceutical representatives provide medicines information on their promoted products to doctors. However, studies have shown that the quality of this information is often low. No study has assessed the medicines information provided by pharmaceutical representatives to doctors in Malaysia and no recent evidence in Australia is present. We aimed to compare the provision of medicines information by pharmaceutical representatives to doctors in Australia and Malaysia. METHODS: Following a pharmaceutical representative's visit, general practitioners in Australia and Malaysia who had agreed to participate, were asked to fill out a questionnaire on the main product and claims discussed during the encounter. The questionnaire focused on provision of product information including indications, adverse effects, precautions, contraindications and the provision of information on the Pharmaceutical Benefit Scheme (PBS) listings and restrictions (in Australia only). Descriptive statistics were produced. Chi-square analysis and clustered linear regression were used to assess differences in Australia and Malaysia. RESULTS: Significantly more approved product information sheets were provided in Malaysia (78%) than in Australia (53%) (P < 0.001). In both countries, general practitioners reported that indications (Australia, 90%, Malaysia, 93%) and dosages (Australia, 76%, Malaysia, 82%) were frequently provided by pharmaceutical representatives. Contraindications, precautions, drug interactions and adverse effects were often omitted in the presentations (range 25% - 41%). General practitioners in Australia and Malaysia indicated that in more than 90% of presentations, pharmaceutical representatives partly or fully answered their questions on contraindications, precautions, drug interactions and adverse effects. More general practitioners in Malaysia (85%) than in Australia (60%) reported that pharmaceutical representatives should have mentioned contraindications, precautions for use, drug interaction or adverse effects spontaneously (P < 0.001). In 48% of the Australian presentations, general practitioners reported the pharmaceutical representatives failed to mention information on PBS listings to general practitioners. CONCLUSIONS: Information on indications and dosages were usually provided by pharmaceutical representatives in Australia and Malaysia. However, risk and harmful effects of medicines were often missing in their presentations. Effective control of medicines information provided by pharmaceutical representatives is needed.

Influence of comorbidities on therapeutic progression of diabetes treatment in Australian veterans: a cohort study.

BACKGROUND: This study assessed whether the number of comorbid conditions unrelated to diabetes was associated with a delay in therapeutic progression of diabetes treatment in Australian veterans. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort study was undertaken using data from the Australian Department of Veterans' Affairs (DVA) claims database between July 2000 and June 2008. The study included new users of metformin or sulfonylurea medicines. The outcome was the time to addition or switch to another antidiabetic treatment. The total number of comorbid conditions unrelated to diabetes was identified using the pharmaceutical-based comorbidity index, Rx-Risk-V. Competing risk regression analyses were conducted, with adjustments for a number of covariates that included age, gender, residential status, use of endocrinology service, number of hospitalisation episodes and adherence to diabetes medicines. Overall, 20,134 veterans were included in the study. At one year, 23.5% of patients with diabetes had a second medicine added or had switched to another medicine, with 41.4% progressing by 4 years. The number of unrelated comorbidities was significantly associated with the time to addition of an antidiabetic medicine or switch to insulin (subhazard ratio [SHR] 0.87 [95% CI 0.84-0.91], P<0.001). Depression, cancer, chronic obstructive pulmonary disease, dementia, and Parkinson's disease were individually associated with a decreased likelihood of therapeutic progression. Age, residential status, number of hospitalisations and adherence to anti-diabetic medicines delayed therapeutic progression. CONCLUSIONS/SIGNIFICANCE: Increasing numbers of unrelated conditions decreased the likelihood of therapeutic progression in veterans with diabetes. These results have implications for the development of quality measures, clinical guidelines and the construction of models of care for management of diabetes in elderly people with comorbidities.

Information from pharmaceutical companies and the quality, quantity, and cost of physicians' prescribing: a systematic review.

BACKGROUND: Pharmaceutical companies spent $57.5 billion on pharmaceutical promotion in the United States in 2004. The industry claims that promotion provides scientific and educational information to physicians. While some evidence indicates that promotion may adversely influence prescribing, physicians hold a wide range of views about pharmaceutical promotion. The objective of this review is to examine the relationship between exposure to information from pharmaceutical companies and the quality, quantity, and cost of physicians' prescribing. METHODS AND FINDINGS: We searched for studies of physicians with prescribing rights who were exposed to information from pharmaceutical companies (promotional or otherwise). Exposures included pharmaceutical sales representative visits, journal advertisements, attendance at pharmaceutical sponsored meetings, mailed information, prescribing software, and participation in sponsored clinical trials. The outcomes measured were quality, quantity, and cost of physicians' prescribing. We searched Medline (1966 to February 2008), International Pharmaceutical Abstracts (1970 to February 2008), Embase (1997 to February 2008), Current Contents (2001 to 2008), and Central (The Cochrane Library Issue 3, 2007) using the search terms developed with an expert librarian. Additionally, we reviewed reference lists and contacted experts and pharmaceutical companies for information. Randomized and observational studies evaluating information from pharmaceutical companies and measures of physicians' prescribing were independently appraised for methodological quality by two authors. Studies were excluded where insufficient study information precluded appraisal. The full text of 255 articles was retrieved from electronic databases (7,185 studies) and other sources (138 studies). Articles were then excluded because they did not fulfil inclusion criteria (179) or quality appraisal criteria (18), leaving 58 included studies with 87 distinct analyses. Data were extracted independently by two authors and a narrative synthesis performed following the MOOSE guidelines. Of the set of studies examining prescribing quality outcomes, five found associations between exposure to pharmaceutical company information and lower quality prescribing, four did not detect an association, and one found associations with lower and higher quality prescribing. 38 included studies found associations between exposure and higher frequency of prescribing and 13 did not detect an association. Five included studies found evidence for association with higher costs, four found no association, and one found an association with lower costs. The narrative synthesis finding of variable results was supported by a meta-analysis of studies of prescribing frequency that found significant heterogeneity. The observational nature of most included studies is the main limitation of this review. CONCLUSIONS: With rare exceptions, studies of exposure to information provided directly by pharmaceutical companies have found associations with higher prescribing frequency, higher costs, or lower prescribing quality or have not found significant associations. We did not find evidence of net improvements in prescribing, but the available literature does not exclude the possibility that prescribing may sometimes be improved. Still, we recommend that practitioners follow the precautionary principle and thus avoid exposure to information from pharmaceutical companies. Please see later in the article for the Editors' Summary.