Conflicts of Interest among Authors of Clinical Practice Guidelines for Glycemic Control in Type 2 Diabetes Mellitus

Background

Conflict of interest (COI) is an important potential source of bias in the development of clinical practice guidelines (CPGs).

Objectives

To examine rates of disclosure of COI, including financial interests in companies that manufacture drugs that are recommended in CPGs on glycemic control in type 2 diabetes mellitus, and to explore the relationship between recommendations for specific drugs in a guideline and author COI.

Methods

We identified a cohort of relevant guidelines from the National Guideline Clearinghouse (NGC) and abstracted COI disclosures from all guideline authors for this observational, cross-sectional study. We determined which hypoglycemic drugs were recommended in each guideline, and explored the relationship between specific disclosures and whether a drug was recommended.

Results

Among 13 included guidelines, the percentage of authors with one or more financial disclosures varied from 0 to 94% (mean 44.2%), and was particularly high for two US-based guidelines (91% and 94%). Three guidelines disclosed no author financial COI. The percentage of authors with disclosures of financial interests in manufacturers of recommended drugs was also high (mean 30%). On average, 56% of manufacturers of patented drugs recommended in each guideline had one or more authors with a financial interest in their company. We did not find a significant relationship between financial interests and whether a drug was recommended in our sample; US-based guidelines were more likely to make recommendations for a specific drug compared to non-US based guidelines.

Discussion

Authors of this cohort of guidelines have financial interests directly related to the drugs that they are recommending. Although we did not find an association between author COI and drugs recommended in these guidelines and we cannot draw conclusions about the validity of the recommendations, the credibility of many of these guidelines is in doubt.     

Conflict of Interest Disclosures for Clinical Practice Guidelines in the National Guideline Clearinghouse

Background

Conflict of interest (COI) is an important potential source of bias in the development of clinical practice guidelines (CPGs) and high rates of COI among guideline authors have been reported in the past. Our objective was to report current rates of disclosure and specific author COI across a broad range of CPGs and to examine whether CPG characteristics were associated with the presence of disclosures and of conflicts.

Methods and Findings

We selected a random sample of 250 CPGs listed in the National Guideline Clearinghouse on November 22, 2010, representing approximately a 10% sample of guidelines listed in the NGC on that date. We abstracted information on author COI from each CPG and examined predictors of the disclosures and COI using a logistic generalized estimating equation regression model. 87% of organizations developing guidelines had a CPG-specific policy, however, 40% of CPGs did not indicate that they had collected disclosures from guideline authors. In addition, 42% of organizations that did collect author disclosures did not have those disclosures available in the public domain. Of CPGs where we had disclosures for all authors, 60% had one or more authors with a conflict. On average, 28% of the authors of CPGs with available disclosures had a COI. Guidelines that were published in journals with an impact factor greater than 5.0 were more likely to have one or more authors with a COI than guidelines not published in journals.

Conclusions

Rates of disclosure of author COI and the public availability of that information are unacceptably low, however rates of COI among guideline authors may have decreased in recent years. Continued efforts are needed to establish and enforce optimal COI policies in clinical practice guideline development in order to minimize the risk of bias associated with those conflicts.     

Conflict of interest in clinical practice guideline development: a systematic review

Background

There is an emerging literature on the existence and effect of industry relationships on physician and researcher behavior. Much less is known, however, about the effects of these relationships and other conflicts of interest (COI) on clinical practice guideline (CPG) development and recommendations. We performed a systematic review of the prevalence of COI and its effect on CPG recommendations.

Methodology/Principal Findings

We searched Medline (1980 to March, 2011) for studies that examined the effect of COI on CPG development and/or recommendations. Data synthesis was qualitative. Twelve studies fulfilled inclusion criteria; 9 were conducted in the US. All studies reported on financial relationships of CPG authors with the pharmaceutical industry; 1 study also examined relationships with diagnostic testing and insurance companies. The majority of guidelines had authors with industry affiliations, including consultancies (authors with relationship, range 6–80%); research support (4–78%); equity/stock ownership (2–17%); or any COI (56–87%). Four studies reported multiple types of financial interactions for individual authors (number of types per author: range 2 to 10 or more). Data on the effect of COI on CPG recommendations were confined to case studies wherein authors with specific financial ties appeared to benefit from the related CPG recommendations. In a single study, few authors believed that their relationships influenced their recommendations. No studies reported on intellectual COI in CPGs.

Conclusions/Significance

There are limited data describing the high prevalence of COI among CPG authors, and only case studies of the effect of COI on CPG recommendations. Further research is needed to explore this potential source of bias.     

Financial Conflicts of Interest and Reporting Bias Regarding the Association between Sugar-Sweetened Beverages and Weight Gain: A Systematic Review of Systematic Reviews

Background

Industry sponsors'' financial interests might bias the conclusions of scientific research. We examined whether financial industry funding or the disclosure of potential conflicts of interest influenced the results of published systematic reviews (SRs) conducted in the field of sugar-sweetened beverages (SSBs) and weight gain or obesity.

Methods and Findings

We conducted a search of the PubMed, Cochrane Library, and Scopus databases to identify published SRs from the inception of the databases to August 31, 2013, on the association between SSB consumption and weight gain or obesity. SR conclusions were independently classified by two researchers into two groups: those that found a positive association and those that did not. These two reviewers were blinded with respect to the stated source of funding and the disclosure of conflicts of interest.We identified 17 SRs (with 18 conclusions). In six of the SRs a financial conflict of interest with some food industry was disclosed. Among those reviews without any reported conflict of interest, 83.3% of the conclusions (10/12) were that SSB consumption could be a potential risk factor for weight gain. In contrast, the same percentage of conclusions, 83.3% (5/6), of those SRs disclosing some financial conflict of interest with the food industry were that the scientific evidence was insufficient to support a positive association between SSB consumption and weight gain or obesity. Those reviews with conflicts of interest were five times more likely to present a conclusion of no positive association than those without them (relative risk: 5.0, 95% CI: 1.3–19.3).An important limitation of this study is the impossibility of ruling out the existence of publication bias among those studies not declaring any conflict of interest. However, the best large randomized trials also support a direct association between SSB consumption and weight gain or obesity.

Conclusions

Financial conflicts of interest may bias conclusions from SRs on SSB consumption and weight gain or obesity. Please see later in the article for the Editors'' Summary     

Clinical Practice Guidelines and Consensus Statements in Oncology – An Assessment of Their Methodological Quality

BackgroundConsensus statements and clinical practice guidelines are widely available for enhancing the care of cancer patients. Despite subtle differences in their definition and purpose, these terms are often used interchangeably. We systematically assessed the methodological quality of consensus statements and clinical practice guidelines published in three commonly read, geographically diverse, cancer-specific journals. Methods Consensus statements and clinical practice guidelines published between January 2005 and September 2013 in Current Oncology, European Journal of Cancer and Journal of Clinical Oncology were evaluated. Each publication was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) rigour of development and editorial independence domains. For assessment of transparency of document development, 7 additional items were taken from the Institute of Medicine’s standards for practice guidelines and the Journal of Clinical Oncology guidelines for authors of guidance documents.MethodsConsensus statements and clinical practice guidelines published between January 2005 and September 2013 in Current Oncology, European Journal of Cancer and Journal of Clinical Oncology were evaluated. Each publication was assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) rigour of development and editorial independence domains. For assessment of transparency of document development, 7 additional items were taken from the Institute of Medicine''s standards for practice guidelines and the Journal of Clinical Oncology guidelines for authors of guidance documents.FindingsThirty-four consensus statements and 67 clinical practice guidelines were evaluated. The rigour of development score for consensus statements over the three journals was 32% lower than that of clinical practice guidelines. The editorial independence score was 15% lower for consensus statements than clinical practice guidelines. One journal scored consistently lower than the others over both domains. No journals adhered to all the items related to the transparency of document development. One journal’s consensus statements endorsed a product made by the sponsoring pharmaceutical company in 64% of cases.ConclusionGuidance documents are an essential part of oncology care and should be subjected to a rigorous and validated development process. Consensus statements had lower methodological quality than clinical practice guidelines using AGREE II. At a minimum, journals should ensure that that all consensus statements and clinical practice guidelines adhere to AGREE II criteria. Journals should consider explicitly requiring guidelines to declare pharmaceutical company sponsorship and to identify the sponsor’s product to enhance transparency.     

From autonomy to accountability: the role of clinical practice guidelines in professional power

Evidence-based medicine (EBM) aims to address the persistent problem of clinical practice variation with the help of various tools, including standardized practice guidelines. Based on a systematic evaluation of the available scientific evidence, these guidelines offer recommendations for clinicians about details of patient care and clinical decision making. Because clinical practice guidelines specify how health care should be performed, they could be considered a threat to clinical and professional autonomy. Inspired by the theory of countervailing powers, this article explores how clinical practice guidelines have shifted the focus of professional power from autonomy to accountability. Professional organizations develop clinical practice guidelines as a service to their members but do not require strict adherence to the guidelines. Indeed, implementation studies show at best a modest change in clinical behavior. Such non-adherence might render a profession vulnerable, however, when third parties seize upon guidelines and offer financial incentives to keep clinicians accountable for delivering optimal patient care.     

Evaluating "payback" on biomedical research from papers cited in clinical guidelines: applied bibliometric study

ObjectivesTo develop a methodology for evaluating the impact of research on health care, and to characterise the papers cited on clinical guidelines.DesignThe bibliographic details of the papers cited in 15 clinical guidelines, developed in and for the United Kingdom, were collated and analysed with applied bibliometric techniques.ResultsThe median age of papers cited in clinical guidelines was eight years; most papers were published by authors living in either the United States (36%) or the United Kingdom (25%)—this is two and a half times more than expected as about 10% of all biomedical outputs are published in the United Kingdom; and clinical guidelines do not cite basic research papers.ConclusionAnalysis of the evidence base of clinical guidelines may be one way of tracking the flow of knowledge from the laboratory to the clinic. Moreover, such analysis provides a useful, clinically relevant method for evaluating research outcomes and different strategies in research and development.     

Health Professionals “Make Their Choice”: Pharmaceutical Industry Leaders’ Understandings of Conflict of Interest

Conflicts of interest, stemming from relationships between health professionals and the pharmaceutical industry, remain a highly divisive and inflammatory issue in healthcare. Given that most jurisdictions rely on industry to self-regulate with respect to its interactions with health professionals, it is surprising that little research has explored industry leaders’ understandings of conflicts of interest. Drawing from in-depth interviews with ten pharmaceutical industry leaders based in Australia, we explore the normalized and structural management of conflicts of interest within pharmaceutical companies. We contrast this with participants’ unanimous belief that the antidote to conflicts of interest with health professionals were “informed consumers.” It is, thus, unlikely that a self-regulatory approach will be successful in ensuring ethical interactions with health professionals. However, the pharmaceutical industry’s routine and accepted practices for disclosing and managing employees’ conflicts of interest could, paradoxically, serve as an excellent model for healthcare.     

A critical appraisal of clinical practice guidelines for the treatment of lower-limb osteoarthritis

Clinical practice guidelines are important tools to assist clinical decision-making. Recently, several guidelines addressing the management of osteoarthritis (OA) have been published. Clinicians treating patients with OA must ensure that these guidelines are developed with consistency and methodological rigour. We undertook a qualitative summary and critical appraisal of six medical treatment guidelines for the management of lower-limb OA published in the medical literature within the past 5 years. A review of these six guidelines revealed that each possesses strengths and weakness. While most described the scope and intended patient populations, the guidelines varied considerably in the rigour of their development, coverage of implementation issues, and disclosure of conflicts of interest.     

A critical appraisal of clinical practice guidelines for the treatment of lower-limb osteoarthritis

Clinical practice guidelines are important tools to assist clinical decision-making. Recently, several guidelines addressing the management of osteoarthritis (OA) have been published. Clinicians treating patients with OA must ensure that these guidelines are developed with consistency and methodological rigour. We undertook a qualitative summary and critical appraisal of six medical treatment guidelines for the management of lower-limb OA published in the medical literature within the past 5 years. A review of these six guidelines revealed that each possesses strengths and weakness. While most described the scope and intended patient populations, the guidelines varied considerably in the rigour of their development, coverage of implementation issues, and disclosure of conflicts of interest.     

Pragmatic randomised controlled trial to evaluate guidelines for the management of infertility across the primary care-secondary care interface

ObjectiveTo investigate the effect of clinical guidelines on the management of infertility across the primary care-secondary care interface.DesignCluster randomised controlled trial.SettingGeneral practices and NHS hospitals accepting referrals for infertility in the Greater Glasgow Health Board area.ParticipantsAll 221 general practices in Glasgow; 214 completed the trial.InterventionGeneral practices in the intervention arm received clinical guidelines developed locally. Control practices received them one year later. Dissemination of the guidelines included educational meetings.ResultsData on 689 referrals were collected. No significant difference was found in referral rates for infertility. Fewer than 1% of couples were referred inappropriately early. Referrals from intervention practices were significantly more likely to have all relevant investigations carried out (odds ratio 1.32, 95% confidence interval 1.00 to 1.75, P=0.025). 70% of measurements of serum progesterone concentrations during the midluteal phase and 34% of semen analyses were repeated at least once in hospital, despite having been recorded as normal when checked in general practice. No difference was found in the proportion of referrals in which a management plan was reached within one year or in the mean duration between first appointment and date of management plan. NHS costs were not significantly affected.ConclusionsDissemination of infertility guidelines by commonly used methods results in a modest increase in referrals having recommended investigations completed in general practice, but there are no detectable differences in outcome for patients or reduction in costs. Clinicians in secondary care tended to fail to respond to changes in referral practice by doctors. Guidelines that aim to improve the referral process need to be disseminated and implemented so as to lead to changes in both primary care and secondary care.

What is already known on this topic

Most previous research into clinical guidelines has focused on their development and implementationEvidence is lacking about the outcomes and costs associated with the use of clinical guidelines

What this study adds

Clinical guidelines that may alter the balance of care between general practice and hospital settings require more intensive implementation than guidelines aimed at either setting on its ownThe cost effectiveness of clinical guidelines should not be assumed     

Canadian physicians' attitudes about and preferences regarding clinical practice guidelines

OBJECTIVE: To assess Canadian physicians'' confidence in, attitudes about and preferences regarding clinical practice guidelines. DESIGN: Cross-sectional, self-administered mailed survey. PARTICIPANTS: Stratified random sample of 3000 Canadian physicians; 1878 (62.6%) responded. SETTING: Canada. OUTCOME MEASURES: Physicians'' use of various information sources; familiarity with and confidence in guidelines; attitudes about guidelines and their effect on medical care; rating of importance of guidelines and other sources of information in clinical decision-making; rating of importance of various considerations in deciding whether to adopt a set of guidelines; and rating of usefulness of different formats for presenting guidelines. MAIN RESULTS: In all, 52% of the respondents reported using guidelines at least monthly, substantially less frequently than traditional information sources. Most of the respondents expressed confidence in guidelines issued by various physician organizations, but 51% to 77% were not confident in guidelines issued by federal or provincial health ministries or by health insurance plans. The respondents were generally positive about guidelines (e.g., over 50% strongly agreed that they are a convenient source of advice and good educational tools); however, 22% to 26% had concerns about loss of autonomy, the rigidity of guidelines and decreased satisfaction with medical practice. Endorsement by respected colleagues or major organizations was identified as very important by 78% and 62% of the respondents respectively in deciding whether to adopt a set of guidelines in their practice. User friendliness of the guidelines format was thought to be very important by 62%; short pamphlets, manuals summarizing a number of guidelines, journal articles and pocket cards summarizing guidelines were the preferred formats (identified as most useful by 50% to 62% of the respondents). CONCLUSIONS: Canadian physicians, although generally positive about guidelines and confident in those developed by clinicians, have not yet integrated the use of guidelines into their practices to a large extent. Our results suggest that respected organizations and opinion leaders should be involved in the development of guidelines and that the acceptability of any proposed format and medium for guidelines presentation should be pretested.     

Promotional tone in reviews of menopausal hormone therapy after the Women's Health Initiative: an analysis of published articles

Background

Even after the Women''s Health Initiative (WHI) found that the risks of menopausal hormone therapy (hormone therapy) outweighed benefit for asymptomatic women, about half of gynecologists in the United States continued to believe that hormones benefited women''s health. The pharmaceutical industry has supported publication of articles in medical journals for marketing purposes. It is unknown whether author relationships with industry affect promotional tone in articles on hormone therapy. The goal of this study was to determine whether promotional tone could be identified in narrative review articles regarding menopausal hormone therapy and whether articles identified as promotional were more likely to have been authored by those with conflicts of interest with manufacturers of menopausal hormone therapy.

Methods and Findings

We analyzed tone in opinion pieces on hormone therapy published in the four years after the estrogen-progestin arm of the WHI was stopped. First, we identified the ten authors with four or more MEDLINE-indexed reviews, editorials, comments, or letters on hormone replacement therapy or menopausal hormone therapy published between July 2002 and June 2006. Next, we conducted an additional search using the names of these authors to identify other relevant articles. Finally, after author names and affiliations were removed, 50 articles were evaluated by three readers for scientific accuracy and for tone. Scientific accuracy was assessed based on whether or not the findings of the WHI were accurately reported using two criteria: (1) Acknowledgment or lack of denial of the risk of breast cancer diagnosis associated with hormone therapy, and (2) acknowledgment that hormone therapy did not benefit cardiovascular disease endpoints. Determination of promotional tone was based on the assessment by each reader of whether the article appeared to promote hormone therapy. Analysis of inter-rater consistency found moderate agreement for scientific accuracy (κ = 0.57) and substantial agreement for promotional tone (κ = 0.65). After discussion, readers found 86% of the articles to be scientifically accurate and 64% to be promotional in tone. Themes that were common in articles considered promotional included attacks on the methodology of the WHI, arguments that clinical trial results should not guide treatment for individuals, and arguments that observational studies are as good as or better than randomized clinical trials for guiding clinical decisions. The promotional articles we identified also implied that the risks associated with hormone therapy have been exaggerated and that the benefits of hormone therapy have been or will be proven. Of the ten authors studied, eight were found to have declared payment for speaking or consulting on behalf of menopausal hormone manufacturers or for research support (seven of these eight were speakers or consultants). Thirty of 32 articles (90%) evaluated as promoting hormone therapy were authored by those with potential financial conflicts of interest, compared to 11 of 18 articles (61%) by those without such conflicts (p = 0.0025). Articles promoting the use of menopausal hormone therapy were 2.41 times (95% confidence interval 1.49–4.93) as likely to have been authored by authors with conflicts of interest as by authors without conflicts of interest. In articles from three authors with conflicts of interest some of the same text was repeated word-for-word in different articles.

Conclusion

There may be a connection between receiving industry funding for speaking, consulting, or research and the publication of promotional opinion pieces on menopausal hormone therapy. Please see later in the article for the Editors'' Summary     

Chemotherapy and zoledronate sensitize solid tumour cells to Vγ9Vδ2 T cell cytotoxicity

Combinations of cellular immune-based therapies with chemotherapy and other antitumour agents may be of significant clinical benefit in the treatment of many forms of cancer. Gamma delta (γδ) T cells are of particular interest for use in such combined therapies due to their potent antitumour cytotoxicity and relative ease of generation in vitro. Here, we demonstrate high levels of cytotoxicity against solid tumour-derived cell lines with combination treatment utilizing Vγ9Vδ2 T cells, chemotherapeutic agents and the bisphosphonate, zoledronate. Pre-treatment with low concentrations of chemotherapeutic agents or zoledronate sensitized tumour cells to rapid killing by Vγ9Vδ2 T cells with levels of cytotoxicity approaching 90%. In addition, zoledronate enhanced the chemotherapy-induced sensitization of tumour cells to Vγ9Vδ2 T cell cytotoxicity resulting in almost 100% lysis of tumour targets in some cases. Vγ9Vδ2 T cell cytotoxicity was mediated by perforin following TCR-dependent and isoprenoid-mediated recognition of tumour cells. Production of IFN-γ by Vγ9Vδ2 T cells was also induced after exposure to sensitized targets. We conclude that administration of Vγ9Vδ2 T cells at suitable intervals after chemotherapy and zoledronate may substantially increase antitumour activities in a range of malignancies. Financial support and conflicts of interest: This study was supported by grants from Medinet (Japan), and Suncorp Metway and Gallipoli Research Foundation (Australia). No financial or commercial interests arise from this study. Informed consent: This study was approved by Human Research Ethics Committees of the University of Queensland and Greenslopes Private Hospital and informed consent was obtained from all subjects.     

Coordinated Primary and Specialty Care for Type 2 Diabetes Mellitus,Guidelines, and Systems: An Educational Needs Assessment

ObjectiveTo determine knowledge, competence, and attitudinal issues among primary care providers (PCPs) and diabetes specialists regarding the use and application of evidence-based clinical guidelines and the coordination of care between PCPs and diabetes specialists specifically related to referral practices for patients with diabetes.MethodsA survey tool was completed by 491 PCPs and 249 diabetes specialists. Data were collected from specialists online and from PCP attendees at live symposia across the United States. Results were analyzed for frequency of response and evaluation of significant relationships among the variables.ResultsSuboptimal practice patterns and interprofessional communication as well as gaps in diabetes-related knowledge and processes were identified. PCPs reported a lack of clarity about who, PCP or specialist, should assume clinical responsibility for the management of diabetes after a specialty referral. PCPs were most likely to refer patients to diabetes specialists for management issues relating to insulin therapy and use of advanced treatment strategies, such as insulin pens and continuous glucose monitoring.A minority of PCPs and even fewer specialists reported the routine use of clinical guidelines in practice.ConclusionThis research-based assessment identified critical educational needs and gaps related to coordinated care for patients with diabetes as well as the need for qualityand performance-based educational interventions. (Endocr Pract. 2011;17:880-890)     

Wall Street's assessment of plastic surgery--related technology: a clinical and financial analysis

Many plastic surgeons develop technologies that are manufactured by Wall Street-financed companies. Others participate in the stock market as investors. This study examines the bioengineered skin industry to determine whether it integrates clinical and financial information as Wall Street tenets would predict, and to see whether the financial performance of these companies provides any lessons for practicing plastic surgeons. In efficient markets, the assumptions on which independent financial analysts base their company sales and earnings projections are clinically reasonable, the volatility of a company's stock price does not irrationally differ from that of its industry sector, and the buy/sell recommendations of analysts are roughly congruent. For the companies in this study, these key financial parameters were compared with a benchmark index of 69 biotech companies of similar age and annual revenues (Student's t test). Five bioengineered skin companies were included in the study. Analysts estimated that each company would sell its product to between 24 and 45 percent of its target clinical population. The average stock price volatility was significantly higher for study companies than for those in the benchmark index (p < 0.05). Similarly, buy/sell recommendations of analysts for the study companies were significantly less congruent than those for the benchmark companies (p < 0.05). These results indicate clinically unrealistic projections for market penetration, significantly high price volatility, and significantly high discordance among professional analysts. In all cases, the market is inefficient-an unusual finding on Wall Street. A likely explanation for this market failure is a cycle of poor clinical correlation when assigning sales projections, which in turn leads to price volatility and discordance of buy/sell recommendations. This study's findings have implications for plastic surgeons who develop new technology or who participate in the equities markets as investors. Plastic surgeons who develop new medical devices or technology cannot universally depend on the market to drive clinically reasonable financial performance. Although inflated sales estimates have benefits in the short term, failure to meet projections exacts severe financial penalties. Plastic surgeons who invest in the stock market, because of their unique clinical experience, may sometimes be in the position to evaluate new technologies and companies better than Wall Street experts. Well-timed trades that use this expertise can result in opportunities for profit.     

Therapeutic Conflicts in Emergency Department Patients with Multimorbidity: A Cross-Sectional Study

Background

Patients with multimorbidity are an increasing concern in healthcare. Clinical practice guidelines, however, do not take into account potential therapeutic conflicts caused by co-occurring medical conditions. This makes therapeutic decisions complex, especially in emergency situations.

Objective

The aim of this study was to identify and quantify therapeutic conflicts in emergency department patients with multimorbidity.

Methods

We reviewed electronic records of all patients ≥18 years with two or more concurrent active medical conditions, admitted from the emergency department to the hospital ward of the University Hospital Zurich in January 2009. We cross-tabulated all active diagnoses with treatments recommended by guidelines for each diagnosis. Then, we identified potential therapeutic conflicts and classified them as either major or minor conflicts according to their clinical significance.

Results

166 emergency inpatients with multimorbidity were included. The mean number of active diagnoses per patient was 6.6 (SD±3.4). We identified a total of 239 therapeutic conflicts in 49% of the of the study population. In 29% of the study population major therapeutic conflicts, in 41% of the patients minor therapeutic conflicts occurred.

Conclusions

Therapeutic conflicts are common among multimorbid patients, with one out of two experiencing minor, and one out of three experiencing major therapeutic conflicts. Clinical practice guidelines need to address frequent therapeutic conflicts in patients with co-morbid medical conditions.     

Advanced therapy medicinal product manufacturing under the hospital exemption and other exemption pathways in seven European Union countries

Background aimsAs part of the advanced therapy medicinal product (ATMP) regulation, the hospital exemption (HE) was enacted to accommodate manufacturing of custom-made ATMPs for treatment purposes in the European Union (EU). However, how the HE pathway has been used in practice is largely unknown.MethodsUsing a survey and interviews, we provide the product characteristics, scale and motivation for ATMP manufacturing under HE and other, non-ATMP-specific exemption pathways in seven European countries.ResultsResults show that ATMPs were manufactured under HE by public facilities located in Finland, Germany, Italy and the Netherlands, which enabled availability of a modest number of ATMPs (n = 12) between 2009 and 2017. These ATMPs were shown to have close proximity to clinical practice, and manufacturing was primarily motivated by clinical needs and clinical experience. Public facilities used HE when patients could not obtain treatment in ongoing or future trials. Regulatory aspects motivated (Finland, Italy, the Netherlands) or limited (Belgium, Germany) HE utilization, whereas financial resources generally limited HE utilization by public facilities. Public facilities manufactured other ATMPs (n = 11) under named patient use (NPU) between 2015 and 2017 and used NPU in a similar fashion as HE. The scale of manufacturing under HE over 9 years was shown to be rather limited in comparison to manufacturing under NPU over 3 years. In Germany, ATMPs were mainly manufactured by facilities of private companies under HE.ConclusionsThe HE enables availability of ATMPs with close proximity to clinical practice. Yet in some countries, HE provisions limit utilization, whereas commercial developments could be undermined by private HE licenses in Germany. Transparency through a public EU-wide registry and guidance for distinguishing between ATMPs that are or are not commercially viable as well as public-private engagements are needed to optimize the use of the HE pathway and regulatory pathways for commercial development in a complementary fashion.     

Working to Improve Care of Hospital Hyperglycemia Through Statewide Collaboration: The Georgia Hospital Association Diabetes Special Interest Group

ObjectiveTo review the efforts of the Georgia Hospital Association Diabetes Special Interest Group (DSIG) to develop and disseminate sample clinical guidelines on management of inpatient hyperglycemia.MethodsBeginning in February 2003, a consortium of physicians and allied health professionals from throughout the state of Georgia began meeting on a frequent basis to formulate a plan to enhance the care of hospitalized patients with hyperglycemia. The immediate goals of the DSIG were the identification and organization of interested stakeholders, the development of consensus sample clinical guidelines, and the dissemination of information.ResultsSince its inception, the DSIG has accomplished the following: development of 7 consensus sample clinical guidelines, construction of a Web site that posts these clinical guidelines and other useful related information and educational materials, and sponsorship of workshops throughout the state of Georgia.ConclusionAs the importance of glucose control in the hospital setting has become increasingly recognized, institutions must find ways of applying results of clinical trials to “real-world” hospital environments. The DSIG is an example of a successful collaboration that could serve as a model for other state hospital organizations that wish to develop programs to enhance the care of inpatients with hyperglycemia. (Endocr Pract. 2007;13:45-50)