How big data’s big bias is bringing noise and conflicts to US drug regulation

Jeanne Lenzer investigates, The BMJ, July 2017

A little known private foundation to support FDA’s “regulatory science” takes money out of the FDA’s coffers to support analyses using levels of evidence recommended by industry; many of the foundation’s directors have financial links to the drug and device makers that the FDA regulates.

Overview
  • No drug risks identified
  • Reagan-Udall Foundation
  • Directors’ ties to industry
  • Panel stacking
  • Funding the foundation
  • Funding the Medical Evidence Development and Surveillance (IMEDS)
  • Light touch FDA

Big data can be used cautiously to examine real world outcomes and to improve surveillance of drug safety. For example, it has been used to identify overuse of some interventions and can show drug and device complications in real world settings rather than idealized controlled trials.

However, big data are a noisy mess, and analyses by entities with profit motives may identify spurious associations that support fast track approvals and indication creep (broadening the indications for drugs and devices).” …

continue reading Jeanne Lenzer investigation Big data’s big bias: bringing noise and conflicts to US drug regulation on The BMJ, 18 July 2017.

Plus de transparence dans l’industrie pharmaceutique et des technologies médicales

Belgique, Ministère des Affaires sociales et de la Santé publique, 23/06/2017

BRUXELLES, 23/06/2017– A l’initiative de la ministre des Affaires sociales et de la Santé publique, Maggie De Block, l’obligation de transparence des firmes pharmaceutiques et des technologies médicales est ancrée juridiquement. La décision d’exécution a été publiée au Moniteur belge, aujourd’hui, 23 juin 2017. Les firmes devront rendre publics tous les avantages et primes qu’elles octroient aux associations de patients et aux professionnels et organisations du secteur de la santé. Il s’agit par exemple du soutien à la formation des professionnels de la santé.
En 2015, les transferts de valeurs provenant de l’industrie pharmaceutique s’élevaient à plus de 138 millions d’euros.

Cette obligation de transparence est inspirée de la loi américaine « Physician Payments Sunshine provision » de 2010, mieux connue sous le nom de «Sunshine Act». Elle est inscrite dans le Pacte d’avenir pour le patient avec l’industrie pharmaceutique et le Pacte des Technologies médicales. La ministre De Block a conclu ces pactes avec les secteurs concernés, respectivement le 27 juillet 2015 et le 5 octobre 2016, dans l’intérêt du patient.

Les deux secteurs ont déjà pris des initiatives dans le passé pour communiquer ce type de données. La ministre De Block fixe maintenant cette obligation de transparence légalement et l’étend à l’ensemble des acteurs des soins de santé. La ministre De Block :

« Le citoyen a le droit de savoir si l’industrie pharmaceutique ou celle des technologies médicales ont un lien avec un prestataire de soins, et si c’est le cas, ce que comprend ce lien. »

Publication
Les citoyens peuvent consulter tous les transferts de valeur de manière simple sur le site internet betransparent.be. Ils sont classés par professionnel de la santé, par organisation de la santé, par association de patients et par entreprise.

L’ensemble des transferts de valeurs octroyés pendant l’année calendrier 2017 devront être rendus publics au plus tard le 30 juin 2018. Les firmes devront communiquer ces données chaque année. A côté de ces infos, les données suivantes seront également mentionnées : les investissements en Recherche & Développement, les frais de séjour lors de congrès scientifiques, les rémunérations de consultance, le soutien financier apporté aux associations de patients, etc.

Gestion
Le site sera géré par beTransparent.be, qui regroupe l’ensemble des acteurs concernés. L’agence fédérale des médicaments et des produits de santé (afmps) est chargée de la supervision des activités de beTransparent.be et du respect de la législation.

En Savoir Plus

Post-marketing studies are not transparent enough and do not improve drug safety surveillance

Contribution of industry funded post-marketing studies to drug safety: survey of notifications submitted to regulatory agencies

BMJ 2017;356:j337 Study (Published 07 February 2017)

Our findings do not support the aspiration of the German Medicinal Products Act that post-marketing studies serve to improve long term drug safety surveillance.

In contrast, we found evidence that drug safety could be jeopardised by the current practice, as post-marketing studies are expected to contribute to pharmacovigilance, but in reality their data and results are treated as business secrets.

Our data support the view that the high remunerations paid by the sponsor to the participating physician could be serving commercial purposes rather than transparent and effective pharmacovigilance.

In our opinion the major problem with post-marketing studies is the confidentiality clauses in the contracts between physicians and sponsors. These contracts impose a major obstacle to scientific evaluation and discussion of post-marketing studies. In the interest of drug safety and public health, post-marketing surveillance should become more transparent. Data about and from such studies should no longer be considered confidential business information but should be made available to independent scientific evaluation and public scrutiny. Such increased transparency would allow future researchers to evaluate whether the changes in 2012 to EU pharmacovigilance legislation have been associated with any material improvements in the situation.

The importance of advising GPs and clinicians on their indispensable role in detecting, diagnosing, and reporting adverse drug reactions cannot be overestimated.

What is already known on this topic

  • Systematic evaluations of post-marketing industry funded trials are sparse
  • The few studies available have criticised post-marketing studies for their low scientific value and lack of scientific integrity and for being seeding trials masking marketing interests of the sponsors as research
  • Current legislation relies on post-marketing studies for drug safety surveillance

What this study adds

  • Post-marketing studies are not serving as a key tool for drug safety surveillance, at least among those registered in Germany
  • Sample sizes are generally too small to allow for the detection of rare adverse drug reactions, and many participating physicians are strictly obliged to maintain confidentiality towards the sponsor about all data, including adverse drug reactions
  • The post-marketing studies analysed are doing no measurable good to patients and could be taking resources away from more effective pharmacovigilance systems
Abstract

Contribution of industry funded post-marketing studies to drug safety: survey of notifications submitted to regulatory agencies, BMJ 2017;356:j337, 07 February 2017.

Objectives
To investigate the practice of post-marketing studies in Germany during a three year period and to evaluate whether these trials meet the aims specified in the German Medicinal Products Act.

Design
Survey of notifications submitted to German regulatory agencies before post-marketing studies were carried out, 2008-10.

Setting
Notifications obtained through freedom of information requests to the three authorities responsible for registering post-marketing studies in Germany.

Main outcome measures
Descriptive statistics of post-marketing studies, including the products under study, intended number of patients, intended number of participating physicians, proposed remunerations, study plan and protocol, and availability of associated scientific publications and reports on adverse drug reactions.

Results

Image credit The BMJ Fig 3 : Example of confidentiality agreement for post-marketing study (source: notification sent by Merck Serono on 18 March 2010 regarding post-marketing study of cladribine)

Information was obtained from 558 studies, with a median of 600 (mean 2331, range 2-75 000) patients and 63 (270, 0-7000) participating physicians per study. The median remuneration to physicians per patient was €200 (€441, €0-€7280) (£170, £0-£6200; $215, $0-$7820), with a total remuneration cost of more than €217m for 558 studies registered over the three year period. The median remuneration per participating physician per study was €2000 (mean €19 424), ranging from €0 to €2 080 000. There was a broad range of drugs and non-drug products, of which only a third represented recently approved drugs. In many notifications, data, information, and results were, by contract, strictly confidential and the sole property of the respective sponsor. No single adverse drug reaction report could be identified from any of the 558 post-marketing studies. Less than 1% of studies could be verified as published in scientific journals.

Conclusions
Post-marketing studies are not improving drug safety surveillance. Sample sizes are generally too small to allow the detection of rare adverse drug reactions, and many participating physicians are strictly obliged to maintain confidentiality towards the sponsor. High remuneration and strict confidentiality clauses in these studies could influence the physicians’ reporting behaviours of adverse drug reactions.

Pharmaceutical industry payments and oncologist drug selection

Payments linked to higher odds of doctors prescribing certain cancer drugs

In preliminary findings that will be presented at the American Society of Clinical Oncology Annual Meeting 2017 in Chicago on Saturday, June 3, researchers show that when physicians had to choose between multiple, on-patent drugs for metastatic kidney cancer and chronic myeloid leukemia, they were more likely to prescribe drugs from companies they had received general payments – for meals, talks, travel, etc. – from.

2017 Study Abstract

Background
Financial relationships between physicians and the pharmaceutical industry are common, and have the potential to influence clinical practice in potentially inappropriate ways. Oncology may be an ideal setting to study the influence of industry payments on physician drug choice given the high levels of competition for market share and high prices commanded by orally administered oncologic drugs.

Methods
We linked the Open Payments database of industry-physician financial transactions with the Medicare Part D Prescriber file by physician name and practice location. We used McFadden’s conditional logit model to determine whether receipt of industry payments was associated with higher odds of using a drug manufactured by the same company. We applied this model to clinical scenarios in which oncologists may choose between multiple, on-patent drugs: metastatic renal cell cancer (mRCC) (sunitinib, sorafenib, and pazopanib) and chronic myeloid leukemia (CML) (imatinib, dasatinib, and nilotinib). The primary, binary independent variable was receipt of payments from a manufacturer of one of these drugs in 2013; the primary dependent variable was choosing that manufacturer’s drug in 2014. We divided industry payments into two categories, research payments and non-research “general” payments (including meals, travel, lodging, and speaking/consulting fees), and analyzed each payment type separately.

Results

More evidence that drug companies are able to influence prescribing practices through gifts to physicians.

Physicians who received general payments from a manufacturer had increased odds of prescribing that manufacturer’s drug for both mRCC (OR: 1.78, 95%CI 1.23-2.57, mean payments $566) and CML (OR: 1.29, 95%CI 1.13-1.48, mean payments $166). Research payments were associated with an increased odds of manufacturer drug use for mRCC (OR: 2.13, 95%CI 1.13-4.00, mean payments $33,391) but not CML (OR: 1.10, 95%CI 0.83-1.45, mean payments $185,763).

Conclusions
Receipt of general payments from pharmaceutical companies is associated with increased prescribing of those companies’ drugs. An association between research payments and prescribing was less consistent. This study suggests that conflicts of interest with the pharmaceutical industry may influence oncologists in high-stakes treatment decisions for patients with cancer.

Sources and Press Release

Many children with bi-polar and ADHD symptoms can be helped without the use of dangerous off-label drugs

Let’s try to find ways to relieve illness without the use of drugs

Video by dr rapp, published on 22 February 2008.

Many children with bi-polar and ADHD symptoms can be helped without the use of dangerous off-label drugs.

There are fast, easy and inexpensive answers available.

Each individual is different and the treatment is rarely identical.

Dr. Doris Rapp has dedicated her life to identifying and providing simple solutions to these and other behavior problems.

Our challenge for physicians is to find fast, easy, safe, effective and inexpensive ways to heal.

Association between physicians’ interaction with pharmaceutical companies and their clinical practices

A systematic review and meta-analysis, 2017

Abstract

Background
Pharmaceutical company representatives likely influence the prescribing habits and professional behaviors of physicians. The objective of this study was to systematically review the association between physicians’ interactions with pharmaceutical companies and their clinical practices.

Methods
We used the standard systematic review methodology. Observational and experimental study designs examining any type of targeted interaction between practicing physicians and pharmaceutical companies were eligible. The search strategy included a search of MEDLINE and EMBASE databases up to July 2016. Two reviewers selected studies, abstracted data, and assessed risk of bias in duplicate and independently. We assessed the quality of evidence using the GRADE approach.

Results
Twenty articles reporting on 19 studies met our inclusion criteria. All of these studies were conducted in high-income countries and examined different types of interactions, including detailing, industry-funded continuing medical education, and receiving free gifts. While all included studies assessed prescribing behaviors, four studies also assessed financial outcomes, one assessed physicians’ knowledge, and one assessed their beliefs. None of the studies assessed clinical outcomes. Out of the 19 studies, 15 found a consistent association between interactions promoting a medication, and inappropriately increased prescribing rates, lower prescribing quality, and/or increased prescribing costs. The remaining four studies found both associations and lack of significant associations for the different types of exposures and drugs examined in the studies. A meta-analysis of six of these studies found a statistically significant association between exposure and physicians’ prescribing behaviors (OR = 2.52; 95% CI 1.82–3.50). The quality of evidence was downgraded to moderate for risk of bias and inconsistency. Sensitivity analysis excluding studies at high risk of bias did not substantially change these results. A subgroup analysis did not find a difference by type of exposure.

Conclusion
There is moderate quality evidence that physicians’ interactions with pharmaceutical companies are associated with their prescribing patterns and quality.

Rapports étudiants en médecine et profs avec liens d’intérêts labos pharmaceutiques non déclarés

Les étudiants en médecine sont-ils sous l’influence des labos pharmaceutiques ?

Pendant ses études, un futur médecin croise des enseignants, des professeurs émérites et des labos pharmaceutiques sans toujours s’en rendre compte.

Le cas échéant, les profs informent-ils leurs étudiants de leurs liens d’intérêts avec les laboratoires?

“Je considère que nos étudiants, ils n’y comprendront rien, ils ont 18 ou 19 ans, je ne vois vraiment pas comment ils pourraient avoir accès à une information éclairée.”

déclare le Pr Gilles Freyer, Vice-Président de la Faculté de Médecine de Lyon Sud.

  • Regardez la vidéo édifiante de l’oeil du 20h, 16 mars 2017.
  • Lisez Les étudiants en médecine sont-ils sous l’influence des labos pharmaceutiques?, blog france tv info, 16 mars 2017.

Sur le même sujet

Treat You Better – Pay For Performance Initiatives in Health Care

Parody of the 2016 Shawn Mendes song

Video by James McCormack, published on 22 January 2017.

For those healthcare providers who struggle with adhering to Pay For Performance measures this may resonate somewhat.

Many pay-for performance initiatives in health care have some major limitations – most importantly P4P initiatives typically forget that individual patients should be involved in heath care decision-making activities.

Comment garder son indépendance face à l’industrie pharmaceutique?

Téléchargez le livret du collectif d’étudiants en médecine de La Troupe du Rire

Téléchargez le livret du collectif d’étudiants en médecine de La Troupe du Rire.

Les liens d’intérêts et l’influence de l’industrie pharmaceutique constituent un risque sanitaire non négligeable.

  • Où se cache cette influence dans notre parcours de soignant ?
  • Comment se manifeste-t-elle ?
  • Pour quelles conséquences ?

C’est à ces interrogations que ce petit livret tente de répondre..

En savoir plus

More than 80 Percent of Patient-Advocacy Organizations are Pharma funded

Conflicts of Interest for Patient Groups

More than 80 percent of patient-advocacy organizations accept funding from drug and medical-device companies. For some patient groups, the donations from industry accounted for more than half of their annual income, and in nearly 40 percent of cases, industry executives sit on governing boards.

2017 Study Abstract

In this examination of 104 large patient-advocacy organizations, 83% receive financial support from drug, device, and biotechnology companies, and industry executives often serve on governing boards. The authors recommend more transparency about industry involvement.

More Information

  • Conflicts of Interest for Patient-Advocacy Organizations, The New England Journal of Medicine, DOI: 10.1056/NEJMsr1610625, March 2, 2017.
  • More Than 80 Percent of Patient Groups Accept Drug Industry Funds, Study Shows, nytimes, MARCH 1, 2017.
  • Pharma Funded “Patient” Groups Keep Drug Prices Astronomical, counterpunch, MARCH 6, 2017.
  • Image credit brewlife, March 13, 2013.