Physicians and the Pharmaceutical Industry: are Doctors really immune to Marketing?

Is a Gift Ever Just a Gift?

business-lunch
The free lunches, merchandise, expensive dinners and golfing holidays – they’re all an investment… Pharmaceutical marketing works… Why else would the industry shell out so much money on marketing to doctors? Image Phillip Capper.

2000 Study Abstract

Context
Controversy exists over the fact that physicians have regular contact with the pharmaceutical industry and its sales representatives, who spend a large sum of money each year promoting to them by way of gifts, free meals, travel subsidies, sponsored teachings, and symposia.

Objective
To identify the extent of and attitudes toward the relationship between physicians and the pharmaceutical industry and its representatives and its impact on the knowledge, attitudes, and behavior of physicians.

Data Sources
A MEDLINE search was conducted for English-language articles published from 1994 to present, with review of reference lists from retrieved articles; in addition, an Internet database was searched and 5 key informants were interviewed.

Study Selection
A total of 538 studies that provided data on any of the study questions were targeted for retrieval, 29 of which were included in the analysis.

Data Extraction
Data were extracted by 1 author. Articles using an analytic design were considered to be of higher methodological quality.

Data Synthesis
Physician interactions with pharmaceutical representatives were generally endorsed, began in medical school, and continued at a rate of about 4 times per month. Meetings with pharmaceutical representatives were associated with requests by physicians for adding the drugs to the hospital formulary and changes in prescribing practice. Drug company–sponsored continuing medical education (CME) preferentially highlighted the sponsor’s drug(s) compared with other CME programs. Attending sponsored CME events and accepting funding for travel or lodging for educational symposia were associated with increased prescription rates of the sponsor’s medication. Attending presentations given by pharmaceutical representative speakers was also associated with nonrational prescribing.

Conclusion
The present extent of physician-industry interactions appears to affect prescribing and professional behavior and should be further addressed at the level of policy and education.

There are few issues in medicine that bring clinicians into heated discussion as rapidly as the interaction between the pharmaceutical industry and the medical profession.

  • More than $11 billion is spent each year by pharmaceutical companies in promotion and marketing, $5 billion of which goes to sales representatives.
  • It has been estimated that $8000 to $13,000 is spent per year on each physician.
  • The attitudes about this expensive interaction are divided and contradictory.
    • One study found that 85% of medical students believe it is improper for politicians to accept a gift,
    • whereas only 46% found it improper for themselves to accept a gift of similar value from a pharmaceutical company.
  • Most medical associations have published guidelines to address this controversy. Perhaps the intensity of the discussion is related to the potential consequences were it confirmed that gifts influence prescription of medication that results in increasing cost or negative health outcomes.

This article addresses the question by way of a critical examination of the evidence. Two review articles have addressed the factors affecting drug prescribing, but only 1 has focused on the impact of the physician-industry interaction on the behavior of physicians. This article critically examines the literature and highlights articles with rigorous study methods.

Sources and more information

The orphan nuclear receptor small heterodimer partner mediates male infertility induced by DES

Nr0b2 reduces testosterone levels after Diethylstilbestrol exposure

lab-mouse image
The study data define Nr0b2 as one of the major actors in the molecular events leading to DES-mediated male infertility. Image via nekrum.

2009 Study Summary

Studies in rodents have shown that male sexual function can be disrupted by fetal or neonatal administration of compounds that alter endocrine homeostasis, such as the synthetic nonsteroidal estrogen Diethylstilbestrol (DES). Although the molecular basis for this effect remains unknown, estrogen receptors likely play a critical role in mediating DES-induced infertility. Recently, we showed that the orphan nuclear receptor small heterodimer partner (Nr0b2), which is both a target gene and a transcriptional repressor of estrogen receptors, controls testicular function by regulating germ cell entry into meiosis and testosterone synthesis. We therefore hypothesized that some of the harmful effects of DES on testes could be mediated through Nr0b2. Here, we present data demonstrating that Nr0b2 deficiency protected mice against the negative effects of DES on testis development and function. During postnatal development, Nr0b2-null mice were resistant to DES-mediated inhibition of germ cell differentiation, which may be the result of interference by Nr0b2 with retinoid signals that control meiosis. Adult Nr0b2-null male mice were also protected against the effects of DES; however, we suggest that this phenomenon was due to the removal of the repressive effects of Nr0b2 on steroidogenesis. Together, these data demonstrate that Nr0b2 plays a critical role in the pathophysiological changes induced by DES in the mouse testis.

Conclusion

Our results demonstrated that Nr0b2 plays a major role in the DES signaling pathway, which affects the development and function of the male reproductive system. We showed that Nr0b2L male mice were protected against the deleterious effects of DES, as they were still able to reproduce even when exposed to high doses of DES. This is caused by the multiple actions of Nr0b2 during testicular development. First, in neonatal animals, Nr0b2 controls germ cell differentiation through inhibition of the retinoid pathway. Nr0b2 regulates the expression of genes involved in the entry and progression of meiosis, such as Stra8 and Nanos3. It also affects meiosis through regulation of the expression of the histone methyltransferase G9a and the subsequent modification of H3K9 methylation marks. These alterations in methylation upon DES exposure induce abnormal chromosomal complexes favoring germ cell apoptosis and could affect the meiosis process. Next to these effects, which appear to be mediated through the estrogenic pathway, DES seems to inhibit germ cell differentiation at P10 through estrogen-independent pathways, as shown by Oct3/4 deregulation specifically in DES-treated mice. Second, in adult animals, the effect of Nr0b2 was dependent on the inhibition of testosterone production, leading to germ cell death. Together, our present data define Nr0b2 as one of the major actors in the molecular events leading to DES-mediated male infertility.

Sources and Full Study
  • The orphan nuclear receptor small heterodimer partner mediates male infertility induced by diethylstilbestrol in mice, NCBI, PMID: 19884658, 2009 Dec.
  • Full study The Journal of Clinical Investigation. 2009;119(12):3752-3764. doi:10.1172/JCI38521. PMC2786790. 2009 Dec.
More DES DiEthylStilbestrol Resources

A very special Happy Mother’s Day to EVERY type of mother!

Portrait of a Mother – Bumps Along the Way Pregnancy Vlog – Pregnant After Stillbirth

No matter if you’ve suffered a miscarriage or stillbirth, have been TTCing for months or years, adopted your children, became a step-mom, lost your perfect baby, or have a bright and cheerful bundle of joy–you are a mother, and today is your day.
A very special Happy Mother’s Day to EVERY type of mother!

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Regional factors driving inappropriate, unnecessary breast cancer imaging

Regional factors may drive inappropriate breast, prostate cancer imaging

A new study has identified a regional-level link between inappropriate low-risk prostate cancer and breast cancer imaging, which suggests the presence of certain regional factors that may be driving this association.

mammography
According to the researchers, higher rates of inappropriate breast cancer imaging may be down to regions’ infrastructure (i.e., access to PET) or culture promoting imaging.

2015 Study Abstract

Importance
The association between regional norms of clinical practice and appropriateness of care is incompletely understood. Understanding regional patterns of care across diseases might optimize implementation of programs like Choosing Wisely, an ongoing campaign to decrease wasteful medical expenditures.

Objective
To determine whether regional rates of inappropriate prostate and breast cancer imaging were associated.

Design, Setting, and Participants
Retrospective cohort study using the the Surveillance, Epidemiology, and End Results–Medicare linked database. We identified patients diagnosed from 2004 to 2007 with low-risk prostate (clinical stage T1c/T2a; Gleason score, ≤6; and prostate-specific antigen level,

Main Outcomes and Measures In a hospital referral region (HRR)-level analysis, our dependent variable was HRR-level imaging rate among patients with low-risk prostate cancer. Our independent variable was HRR-level imaging rate among patients with low-risk breast cancer. In a subsequent patient-level analysis we used multivariable logistic regression to model prostate cancer imaging as a function of regional breast cancer imaging and vice versa.

Results
We identified 9219 men with prostate cancer and 30 398 women with breast cancer residing in 84 HRRs. We found high rates of inappropriate imaging for both prostate cancer (44.4%) and breast cancer (41.8%). In the first, second, third, and fourth quartiles of breast cancer imaging, inappropriate prostate cancer imaging was 34.2%, 44.6%, 41.1%, and 56.4%, respectively. In the first, second, third, and fourth quartiles of prostate cancer imaging, inappropriate breast cancer imaging was 38.1%, 38.4%, 43.8%, and 45.7%, respectively. At the HRR level, inappropriate prostate cancer imaging rates were associated with inappropriate breast cancer imaging rates (ρ = 0.35; P < .01). At the patient level, a man with low-risk prostate cancer had odds ratios (95% CIs) of 1.72 (1.12-2.65), 1.19 (0.78-1.81), or 1.76 (1.15-2.70) for undergoing inappropriate prostate imaging if he lived in an HRR in the fourth, third, or second quartiles, respectively, of inappropriate breast cancer imaging, compared with the lowest quartile.

Conclusions and Relevance
At a regional level, there is an association between inappropriate prostate and breast cancer imaging rates. This finding suggests the existence of a regional-level propensity for inappropriate imaging utilization, which may be considered by policymakers seeking to improve quality of care and reduce health care spending in high-utilization areas.

Sources and more information

“How to” honour your Childlessness on Mother’s Day

Gateway Women, the global friendship and support network for childless women

For many DES daughters, sadly, the greatest right of women has been stolen! For those of us who have experienced miscarriages, who want to have kids but are struggling or unable to, Mother’s Day serves as a stark reminder filled with personal sorrow…

mothers-day-ecard image
You can find out how to honour your childlessness this Mother’s Day by reading Jodykat’ post on Gateway Women.

Yesterday, Jody Day said:

  • For those of us in the UK, we get two onslaughts of media around the day – both on our own Mothering Sunday and then on the US and global Mother’s Day celebrated in May. A double-dose of smugness, cloying sentimentality, alienation and disenfranchised grief. Hooray – let’s all buy cards for that!
  • Silencing ourselves for fear of sounding bitter is much more likely to make us bitter. We need to understand that anger is an entirely valid emotional response to the unfairness we’re having to make our peace with.
  • Once we learn to acknowledge our grief and to do our grief work, we can experience the healing that is its gift. This year, do something differently and honour yourself and your childlessness on Mother’s Day.

Find lots of great suggestions on how to honour your childlessness this Mother’s Day by reading Jodykat’ post on Gateway Women, 13 March 2015.

More about DES pregnancy risks and DES and infertility, pregnancy studies…

Imagining the Future of Medicine

Ben Goldacre was speaking in the home of the BBC Proms on recent progress in promoting transparency in clinical trials

As part of its mission to promote access to the arts and sciences, the Royal Albert Hall hosted an historic event on Monday 21 April 2014, curating a spectacular and provocative programme of talks from world experts celebrating innovation, imagination, inspiration and their passion for a better future in health and medicine.

More information
  • Ben Goldacre, former TED and TEDMED speaker, is a doctor, academic, campaigner and bad science writer whose work focuses on uses and misuses of science and statistics. He is the founder of the All Trials campaign and a keen advocate for clinical transparency.
  • Video published on 10 Jun 2014 by Royal Albert Hall.
  • Watch more research videos on @DES_Journal YT channel.

Pesticide EDCs found in Samples of Women’s Hair

Nineteen endocrine disrupting pesticides found in samples of women’s hair

Hair samples analysis found an average of 21 EDCs per woman, including 19 pesticide EDCs.

The content on this post is produced by HEAL and Générations Futures.

To what extent are women in the child bearing age group exposed to endocrine disrupting pesticides? The fourth part of a study series by French NGO Générations Futures’ provides results of human biomonitoring for endocrine disruptors in samples of women’s hair.

Endocrine disruptors:
Endocrine disrupting chemicals (EDCs) are chemicals that can affect the hormonal system of the body and produce adverse effects on the individual or his or her descendants. Unborn and young children are most at risk of being exposed to these substances. A recent study showed that the impact of these EDCs could have significant costs for society (between 1 and 2% of GDP in Europe!).

Act now:
To demonstrate the urgency of preventive action in the field of endocrine disruptors, Générations Futures decided to carry out a series of EXPPERT reports (French abbreviation for exposure to endocrine disruptors – EXPosition aux PERTurbateurs endocriniens), which show that the presence of EDCs in our environment leads to significant population exposure. Since young and unborn children are especially vulnerable, Générations Futures wanted to identify the extent to which vulnerable groups are exposed to EDCs, including in utero.

A novel and targeted survey:
The EXPPERT survey 4 puts the focus on the exposure of women of childbearing age who are living in urban areas in the region Ile de France (greater Paris area). The investigation was carried out by an independent research laboratory using samples of a strand of hair from 29 women. The samples were collected between March and October 2014. Only 28 samples were analysed as one of the hair samples was found to be inadequate. The laboratory work was carried out in early 2015 testing for 64 suspected endocrine disrupting chemicals, including 54 pesticides or pesticide metabolites, six brominated flame retardants and four PCBs.

Results:
The synthesis results confirmed our fears. An average of 21 EDCs were found per woman, including 19 pesticide EDCs. The number of EDCs found ranged from 32 to 12 per hair sample. In terms of weight, the lowest average amount of EDC residues per sample was 109.39 picogramme/milligram. The maximum amount per sample was 387.27 pg/mg (in comparison to 24.14 pg/mg for the lowest one). In other words, there was a 1:16 ratio between the less contaminated and most contaminated!

“These results show that all these women in childbearing age are contaminated. We are very concerned about the possible effects for the women’s children later in their lives. However, significant differences exist between individuals demonstrating that the environment and/or diet of these women play an important role in their level of exposure to EDCs. We must act on these factors to reduce to exposures to the maximum extent.”

“We have taken note of the progress of the French National Strategy on EDCs (SNPE) in taking into account the need to reduce the EDCs exposure of citizens. It is now time for the European Commission to finally publish a protective definition of EDCs, which will enable the EU Regulations on pesticides and biocides to be fully implemented.”

says François Veillerette, spokesperson for Générations Futures.

Breast Cancer in Transgender People: a Ten-Case Study

Transgender people do not face higher breast cancer risk

Transgender American Veterans Association logo
Ten transgender veterans with a qualifying psychiatric diagnosis were identified as having confirmed breast cancer. Family histories of breast cancer should be elicited from all transgender persons as part of their routine medical care.

2015 Study Conclusions

Breast cancer in transgender patients is rarely reported, and when it is, it is often in association with the receipt of CSH and mentioned as a potential adverse effect of cross-sex hormones (CSH). This report expands the number of reported cases from 15 (10 in male-to-female (MtF), 5 in female-to-male (FtM)) to 25 (13 in MtF, 12 in FtM) in the English literature. Maglione and colleagues, reporting on two cases, concluded that breast cancer occurs in MtF transsexuals who receive “high doses of exogenous estrogens,” which results in an increased risk of breast cancer. Researchers using large cohorts of transgender/transsexual patients followed prospectively have not detected an increased incidence relative to the general population. However, breast cancer can occur, in theory, in the absence of known CSH treatment, in persons with a diagnosis of gender dysphoria, or in a way that is associated with, but unrelated, to gender dysphoria. Given that it is well known that patients who seek CSH treatment from medical sources may also obtain CSH from nonmedical sources in unknown quantities, it is difficult to conduct dose–response studies linking CSH dose/exposure to breast cancer outcomes. It should be noted that this case series derives only from transgender veterans who were identified based on a clinical, psychiatric diagnosis. It is likely that there are many more veterans who self-identify as transgender who did not receive one of the four qualifying psychiatric diagnoses. The number of breast cancer cases in those veterans cannot be determined.

These 10 case reports do not attempt to link CSH to outcome, especially given the fact that provision of CSH treatment was not openly available to gender dysphoric veterans until 2011. Therefore, the VHA EHR for these cases include only information about CSH provided by VHA clinicians. All three birth sex male cases in this series presented with late-stage disease and died from metastatic cancer, whereas the birth sex female patients with gender dysphoria had all been treated and, in all but one case, had survived at least 2 and as long as 25 years after initial diagnosis or at the end of the observation period.

Although apparently rare, breast cancer does occur in transgender people of both birth sexes, and screening methods generally in place for nontransgender persons should be sensitively discussed and applied by clinicians providing transgender healthcare, whether or not CSH medications are utilized. In addition, family histories of breast cancer should be elicited from all transgender persons as part of their routine medical care.

Sources and more information
  • Breast Cancer in Transgender Veterans: A Ten-Case Series, online liebertpub, DOI: 10.1089/lgbt.2014.0123, March 2015.
  • Transgender People Do Not Face Higher Breast Cancer Risk, Study Shows, news health, March 11, 2015.

Risperdal: Dangerous Side Effects in Children and Young Adults

Risperdal®: Risk of Breast Development in Boys

Attorney Stephen Sheller of the Philadelphia law firm Sheller, P.C. discusses the dangerous side effects of Risperdal®, including gynecomastia (development of breasts in male children).

More information

1 in 5 women undergoing hysterectomy in the U.S. may not need the procedure

Use of other treatments before hysterectomy for benign conditions in a statewide hospital collaborative

woman-who-undergo-hysterecteroctomy image
This study provides evidence that alternatives to hysterectomy are underutilized in women undergoing hysterectomy for abnormal uterine bleeding, uterine fibroids, endometriosis, or pelvic pain.

It is estimated that one in three women in the United States will have had a hysterectomy by the age of 60.

Although the numbers of hysterectomies are decreasing, a University of Michigan-led study of nearly 3,400 women in Michigan who underwent hysterectomy for benign indications reveals that alternatives to hysterectomy are being underused and that treatment guidelines are often not followed.

Post-surgical pathology showed that nearly one in five (18%) of hysterectomies that were done for benign indications were unnecessary, and that nearly two in five (37.8%) of women under 40 had unsupportive pathology.

Sources and more information

  • Use of other treatments before hysterectomy for benign conditions in a statewide hospital collaborative, ajog, doi.org/10.1016/j.ajog.2014.11.031, March 2015.
  • Nearly 1 in 5 women who undergo hysterectomy may not need the procedure, University of Michigan, JANUARY 06, 2015.
  • Almost 1 in 5 hysterectomies are ‘unnecessary,’ study finds, medicalnewstoday, 11 January 2015.
  • Nearly One in Five Women Who Undergo Hysterectomy May Not Need the Procedure, elsevier, January 6, 2015.