Author: Deanna Puglia

Corporate Integrity Agreements

Throughout the summer I’ve dedicated several posts to the ways that medical and pharmaceutical publishing should be ethically conducted, according to established requirements and guidelines.

However, I’m sure it comes as no surprise that pharmaceutical companies have consistently failed to play by these rules. Headlines such as “GlaxoSmithKline to Plead Guilty and Pay $3 Billion to Resolve Fraud Allegations and Failure to Report Safety Data,” and “Bristol-Myers Squibb to Pay More Than $515 million to Resolve Illegal Drug Marketing and Pricing Allegations,” are proof that these companies are not always committed to high ethical standards of practice.

Although industry standards such as the ICMJE and GPP3 guidelines are almost universally accepted, they are not laws and are therefore not usually enforceable.

However, when pharmaceutical and biotech companies fall under Federal investigation, the Office of the Inspector General (OIG) can make them agree to abide by a Corporate Integrity Agreement (CIA) as part of their legal settlement.

These CIAs legally obligate companies to abide by many of the tenets of the previously mentioned guidelines and ensure ethical practice by imposing requirements such as:

  • hiring a compliance officer/appointing a compliance committee
  • developing written standards and policies
  • implementing a comprehensive employee training program
  • retaining an independent review organization (IRO) to conduct annual reviews
  • restricting employment of ineligible persons (people who have been flagged for unethical behavior)
  • providing an implementation report and annual reports to OIG on the status of compliance activities

If a company is non-compliant with their CIA, they risk having their product pulled from the list of products that can be reimbursed through Federal health care programs such as Medicare and Medicaid. This loss would be a crippling financial hit to most companies, making compliance with these agreements a high priority.
In this way, the industry can be kept in check and forced to behave in a more ethical manner.

Research Dissemination: Part 2

The most highly regarded place to publish medical research findings is in a peer-reviewed scholarly journal. However, journals are not all considered equal.


Most people have at least heard of the so-called “top-tier” journals including The Journal of the American Medical Association (JAMA), the British Medical Journal, and the New England Journal of Medicine. There are also mid-tier journals which are still respectable, but less competitive, and then there are lower quality journals whose standards and peer review process are much less rigorous (or non-existent) and consequently are taken much less seriously by the medical community.  

The dream is usually to have an article published in a top-tier journal, however, this is not always the best choice depending on the content and goal of a paper. If a paper does not present novel and/or ground-breaking findings, it is probably not worth an author’s’ time to submit it to a top journal and then wait, only to be rejected. Also, if authors’ want to get the results of a study published quickly so that the data is publicly available (for instance to help support an application for FDA approval), it is probably better to go with a less prestigious journal that has a higher acceptance rate or a less rigorous review process.

In addition to journal prestige, there are many other factors that must also be considered when deciding where to submit a manuscript. For example, medical specialty, target audience, impact factor, primary language or region, length limits, and allowance of figures and other supplementary materials are all potential considerations.

Due to the complexity of the factors that weigh into this decision, many medical publications agencies offer assistance with target journal selection by researching and compiling this information for authors so that they can more easily make a decision based on the variables that are most important to them for a particular manuscript.

 
Getting the right information in front of the right audience in a timely manner is critically important in fields such as medicine and pharmaceuticals since that information could potentially affect the lives and well-being of countless individuals.

Research Dissemination: Part 1

After a clinical trial or other medical study has been conducted and the researchers have planned out the ways in which they want to structure the results for disseminationthey next need to actually make that information public in the form of one or more medical publications. These publications typically take the form of posters, presentations, and journal manuscripts.

These publications all require a brief written summary known as an abstract. An abstract includes an overview of each relevant section of a medical publication including the study’s objectives, methods, results, and a discussion of the main conclusions.

For conferences, abstracts are typically developed and submitted as a first step in the acceptance process. The conference committee will then use the submitted abstract to decide whether or not to include a poster or presentation about that study as part of the conference. Once an abstract has been accepted to the conference, the authors can then create a poster or slide deck to present.

Because researchers want to get the maximum bang for their buck when it comes to their study data, most research findings will be presented as a poster or an oral presentation at a medical conference first, then be expanded into a full manuscript for publication in an academic journal.

 
Manuscripts allow researchers to provide a more detailed description of a study’s results and implications and are also able to reach a wider audience. We’ll talk more about manuscripts in next week’s post so be sure to check back on Monday.

Publication Planning: You have the data, now what?

Research, in any field, tends to be time-consuming and expensive. This is especially true of large-scale medical research trials. Therefore physicians and pharmaceutical companies, just like researchers in other fields, want to make optimal use of their research activities by producing as many publications from the resulting data as possible.

There are limits to how far these boundaries can be pushed, however. For example, duplicate publications are generally not permissible. This “double-dipping” includes publishing or presenting an identical work in multiple journals or at multiple conferences, but it also bars researchers from reworking a published piece in a way that does not contribute any new knowledge or insights to the results that were originally published.

One study usually measures a large number of variables and can therefore still be broken down into countless publications without violating sanctions against duplicate publications. For a clinical trial of a particular drug, for example, publications could focus on different outcome measures, such as the mechanism of action, safety, efficacy, economic considerations, administration, adherence, etc. Different publications could also examine these variable in various subgroups, such as pregnant women, the elderly, patients with certain co-morbidities, etc.   

In order to balance the desire for publication volume with the need to be ethically responsible by only publishing works that have scientific value, it is essential that large organizations and companies engage in publication planning activities. By convening a group of stakeholders at a publication planning meeting, an organization or company can lay out all of their available study data and determine what can and should be published from it.

In addition, gap analyses can be conducted to determine the topics or types of information that are missing in the current body of literature which can then serve as basis for future research studies intended to produce that information.

In this way, the cycle of medical research and publishing is continually pushed forward to produce new and valuable knowledge, both for the research community and for healthcare providers.

Authorship of Medical Publications

Last week I briefly introduced the concept of professional medical writers. These individuals are hired to write or create medical publications (such as abstracts, journal articles, and conference posters or presentations) on behalf of, or in collaboration with the actual researchers. Medical writers are often used because researchers do not have the time, interest, or the writing expertise to create high quality, publishable work in a timely manner. However, the listed authors still need to be involved in the writing process, and have specific obligations to fulfil in order to qualify as an author.

The International Committee of Medical Journal Editors (ICMJE) recommends that authorship be based on the following 4 criteria: http://www.icmje.org/icmje-recommendations.pdf

  1. Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; AND
  2. Drafting the work or revising it critically for important intellectual content; AND
  3. Final approval of the version to be published; AND
  4. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Authorship is one of the major ways in which researchers get credit for the work that they do, which in turn often leads to professional and financial benefits. However, being designated as an author also carries a level of responsibility, as it serves as a public acknowledgement that an individual is willing and able to vouch for a publication and field any questions or critiques that may arise after publication of the work. Therefore, it is important that ethical authorship practices continue to be upheld, and that medical writers are used appropriately.

Ghost Writing

In addition to the history of suppressing study results, another ethically dubious practice that used to occur regularly in the history of medical publishing was a practice known as ghost writing. Ghost writing is when someone other than one of the listed authors writes (and often directs) the content of a publication without their participation being disclosed.

In addition, prominent physicians or researchers in a particular specialty were sometimes added to a publication as a ghost author (a person who was not actually involved with the research or the writing of the publication) in order to increase the credibility, prestige, or attention given to the publication by the medical community. Authorship was also sometimes used as a form of compensation or reward, another practice which now violates accepted ethical guidelines.

While ghost writing and ghost authorship is no longer an acceptable practice, due to many medical researchers’ lack of time or writing expertise, many now employ professional medical writers to help with the creation of a publication. Medical writers are professionals who have professional obligations to uphold the ethical practice of writing and publishing medical research, and who ensure the proper adherence to authorship guidelines is observed. In addition, the use of medical writers should always be disclosed by the authors, usually in the acknowledgment section of the publication, in order to keep the process transparent.

However, if authors still aren’t actually doing the bulk of the writing, how do you determine who qualifies as an author?

I’ll address this question in next week’s post. Until then, feel free to share your thoughts in the comments below.

Celebrating Freedom from Disease

Happy 4th of July!

Today is the day that we celebrate freedom in the U.S. However, most of us don’t think about, or we simply take for granted, the successes that have been achieved and the continued fight being waged to be free from disease.

Through public health initiatives like improved sanitation, the initiatives and infrastructure to ensure clean drinking water, and the use of medical advances such as vaccinations and antibiotics, the US is now free, or well on its way to becoming free, from numerous pathogens and infectious diseases.

The most recent data from the CDC concerning reported cases of infectious diseases showed that there were zero reported cases of smallpox, polio, diphtheria, and yellow fever in the U.S., along with staggeringly low numbers of several other diseases, like cholera, that were previously responsible for thousands of deaths.

 

So this Independence Day, enjoy all of your freedoms and have a happy and healthy celebration!

Disease Chart

Data taken from Summary of Notifiable Infectious Diseases and Conditions — United States, 2013

 

Considerations for Ethical Research and Medical Publishing: Part II

Last week I touched on the way in which pharmaceutical marketing and research activities are separated to decrease the chance of bias or unethical practices in medical research. Today I want to briefly introduce some other guidelines that exist to regulate and guide medical research and publishing.

The International Committee of Medical Journal Editors (ICMJE) is one of the leaders in establishing guidelines and recommendations for ethical medical research practices, including both the way the research is conducted, as well as the way in which the results are reported and published. Major medical journals, such as JAMA, the New England Journal of Medicine, the British Medical Journal, and more, require that studies published in their journals abide by these ethical guidelines.

Contrary to what had previously occurred throughout the history of medical research and publishing, individuals and organizations that conduct medical research are now obligated to publish all of their results (even if they’re negative). This newer industry norm was implemented in response to critiques of companies who selectively published only the studies or trials that showed their product in a positive light, a practice that is now considered biased, misleading, and incredibly unethical.

Anti-bribery statutes and requirements to disclose payments and other transfers of value from industry to health care providers, as well as the required disclosure by all authors of their potential conflicts of interest, such as being employed by the pharmaceutical industry or being in some other position to gain financially from the success or sale of a drug, are additional safeguards against biased and unethical practices.

 

For more information about the guidelines and recommendations guiding medical research and publishing, check out these resources:

Is industry sponsorship a problem? Considerations for ethical research and medical publishing.

Clinical research and other drug development and testing activities can be funded, or “sponsored,” by a number of sources, including physicians, universities, government agencies, special interest groups, and pharmaceutical companies. Many people have an understandable concern regarding the reliability of research funded by the pharmaceutical companies that stand to make a profit from the drugs being tested.

While these conflicts of interest will probably always be a concern, it is important to note that there are increasingly more regulations and safeguards being put into place both within the industry and from external sources like the federal government in order to encourage the use of ethical practices in medical research and publishing.

I was also skeptical of the legitimacy and/or motives behind industry-sponsored research, however, what I didn’t realize until I began working within the medical publishing industry was the extent to which research and marketing activities are deliberately segregated by pharmaceutical companies.

For example, the parent company at which I’m currently interning encompasses both a medical publishing agency and a health care marketing agency. Although everyone works in the same building, the agency’s pharmaceutical clients generally require that any of the agency’s staff members who are involved with marketing or advertising for their company not be involved with the planning or publishing of the clinical research being conducted for their products.

So, contrary to what some may perceive to be true, it is not the case that marketing teams are soliciting particular studies or data to be collected in order to help them sell a product. Instead, physicians and researchers are designing and conducting studies based on the scientific and clinical value of the data being produced. In this way, the scientific information is originating from scientists and medical professionals and then being provided to marketing and advertising departments, and not the other way around.

Come back next week for part two of this discussion on the ethical considerations involved in medical publishing.

Inside Medical Publishing: What information is being published?

Last week we discussed the basics of what medical publishing is and why it’s important. Today I want to look at the actual substance of what’s being published. There are many different types of information that are published or presented in the medical community, including original research, meta-analyses, systematic reviews, case studies, review articles, editorials, and more. Of these types of medical publications, the most familiar and most common is the reporting of the methods and results of clinical studies, both observational studies and controlled clinical trials.

The purpose of these studies can vary but generally they fall into one of the following categories; assessing the safety or efficacy of a drug, device, procedure, or lifestyle; investigating or testing methods for identifying and diagnosing conditions; comparing interventions or care models; determining risk factors and effects of conditions; or determining methods for improving quality of life.

Clinical trials of drugs in particular consist of a major, multi-step research process that is highly regulated. These trials fall into one of 5 phases (from 0-4) which range from isolating and testing potentially useful compounds, to continued long-term studies of a drug’s safety and efficacy after it hits the market. To read more about these clinical trial phases, check out the FDA’s more detailed description here.

Also, if you’re interested in the kinds of clinical research being conducted or you’d like to be involved as a research participant, you can check out the U.S. clinical trials registry where researchers post information about their studies, recruit study participants, and even sometimes post their results for the public to see.