Filed under: Bioethics, Clinical Research, Drugs & Devices, Intellectual Property, Privacy, Transparency
We are very pleased to welcome Dana Darst, a Master of Science in Jurisprudence candidate in Health Law and Intellectual Property Law here at Seton Hall, to the blog today.
In recent years, biopharmaceutical research and development organizations have established partnerships with academic institutions and start-up biotechnology companies to drive external innovation, complementary to their own in-house advancements in life sciences. Companies such as Pfizer, Johnson & Johnson and Bayer have opened innovation centers of excellence globally, in start-up biotechnology- and academia-rich hubs such as Boston, San Francisco and Shanghai, as part of an effort to accelerate new product development and commercialization.
More recently, the industry has commenced driving innovation via sharing clinical study protocols and patient-level treatment information at the request of qualified external researchers. An objective of this undertaking is to enhance public health via data transparency. This may increase efficiencies by helping researchers avoid unnecessary use of resources for new studies, when relevant clinical outcomes data exists from previous studies. In addition, it may reduce risks for future research subjects.
On January 30, 2014, Janssen Research and Development, LLC (a Johnson & Johnson subsidiary) and The Yale School of Medicine’s Open Data Access Project (YODA) announced a pioneering partnership model for sharing clinical trial data. Under their agreement, YODA will review all clinical trial data requests on Janssen’s behalf, as an independent third-party. In a press release, J&J’s Chief Medical Officer, Joanne Waldstreicher, MD, stated that their collaboration will “[e]nsure that each and every request for access to [their] pharmaceutical clinical data is reviewed objectively and independently.” She further stated that “[t]his represents a new standard for responsible, independent clinical data sharing.” Other biopharmaceutical companies sharing clinical trial data do so by reviewing data requests directly as they are received from qualified external researchers. Also, some have voluntarily adopted the Principles For Responsible Clinical Trial Data Sharing, jointly published by the Pharmaceutical Research Manufacturers of America (PhRMA) and European Federation of Pharmaceutical Industries and Associations (EFPIA), and implemented on January 1, 2014.
Under the PhRMA-EFPIA guidelines, “Biopharmaceutical companies are committed to enhancing public health through responsible sharing of clinical trial data in a manner that is consistent with the following Principles”: (1) Safeguarding the privacy of patients, (2) Respecting the integrity of national regulatory systems, and (3) Maintaining incentives for biomedical research. The guidelines provide a framework for life sciences companies to request patient-level data and study protocols. Additionally, the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) have proposed policies to increase transparency of clinical trial data. As Carl Coleman discussed here, both agencies have addressed the importance of patient and study de-identification.
So, what potential implications might clinical trial data sharing have on biopharmaceutical innovation? The Institute of Medicine (IOM) et al. recently published a report, Discussion Framework for Clinical Trial Data Sharing: Guiding Principles, Elements and Activities, as a framework for further discussion and public comment on how data from clinical trials might best be shared. It provides four guiding principles for consideration which include (1) respecting individual participants, (2) maximizing benefits to participants in clinical trials and to society, while minimizing harm, (3) increasing public trust in clinical trials, and (4) carrying out sharing of clinical trial data in a manner that enhances fairness.
The report does not provide conclusions or recommendations, which are expected to be developed and published approximately 17-months from the project’s start in August 2013. However, the IOM Committee, which includes a diverse group of representatives from government, charitable foundations, academia, healthcare institutions and private industry, has posed several potential implications of trial data sharing for consideration.
From a societal perspective, sharing clinical trial data could increase accuracy, reduce bias and provide a more comprehensive picture of a drug’s benefits and risks. In addition, data sharing could potentially improve efficiency and safety of the clinical research process. For example, it could reduce potential duplication of efforts and costs of future studies, and help to avoid unnecessary harm to patients. Furthermore, it may provide additional information to healthcare professionals and patients that can be utilized to make better informed decisions.
Alternatively, data sharing could lead to invasions of patient privacy or breaches of confidentiality, which may ultimately harm participants, either socially or economically. Moreover, it could reduce incentives for study sponsors to invest their limited resources (e.g. time, budget, FTEs) on additional trials, which could ultimately inhibit innovation. As the IOM Committee explains:
For example, data sharing might allow confidential commercial information (CCI) to be discerned from the data. Competitors might use shared data to seek regulatory approval of competing products in countries that do not recognize data exclusivity periods or that do not grant patents for certain types of research.
Sharing clinical study protocols and patient-level trial data could have benefits for society and healthcare, which outweigh the risks. The IOM is planning to include an analysis of risks and benefits in their final report. As academic, life sciences and start-up biotech entities increasingly share industry-driven trial data, a prudential approach should be taken to protect the confidentiality and intellectual property of all stakeholders involved. Specifically, data should be adequately redacted prior to disclosure to eliminate confidential information—as recommended by the EMA and U.S. FDA. Biopharmaceutical Innovation is driven by authors and inventors that rely on exclusive, protected rights granted for limited times. As the IOM committee works toward establishing guidelines, adherence to their guiding principles to address these protected rights will be vital.
To obtain additional information or provide public comments on the IOM project, visit their website at: http://www8.nationalacademies.org/cp/projectview.aspx?key=49578.
The Internet, Privacy, and Public Health: How Social Media and Big Data are Changing the Landscape of Surveillance and Research
Online social networks have potential to change the nature, speed, and scope of public health surveillance and research by offering a real-time stream of user-generated updates from millions of people around the world. In recent years, systems using informal data mined from social media sources have been credited with reducing the time it takes to detect an emerging outbreak, preventing governments from suppressing outbreak information, facilitating public health responses, and contributing to health risk behavior research in a quick and cost-efficient manner.
Despite the inherent public nature of social media, there are many ethical implications inherent in the systematic acquisition of personal information, especially that pertaining to health. Concerns surrounding social network data analysis include issues of privacy, data quality, public panic, autonomy, access, and informed consent. While online social network data analysis holds great promise, it is essential that this valuable data be systematically harnessed in compliance with the law and ethical principles to yield population-level health benefits.
Advancements in information and communication technologies distort the boundaries between what is public and what is private. Users of online social networks often share identifiable information about themselves, including their full names, birthdates, email addresses, GPS coordinates, and job titles. By providing researchers with rich, ready-made data sets, social media is incentivizing researchers to develop innovative methods to search the Internet for health-related information. The mining and mapping of social networks have become a common practice, from market research to medical studies. However, it is important then to consider what obligations researchers and public health officials have in meeting their online subjects’ expectations of privacy.
The Code of Federal Regulations governing human subject research, 45 C.F.R. § 46.102, defines private information as individually identifiable information about behavior “that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public.”
While mining publicly available data from open sources is within the letter of the law, it raises a number of ethical issues. Some might argue it seems unreasonable that a public posting on a public site can hold an expectation of privacy. However, privacy can conceptually be considered to be an individual’s right to determine what information one would like to share with others and the ability to control when others can access that information. While the practice of data mining is growing, many social media users are unaware of how public their data truly is.
Researchers must take into consideration the level of sensitivity of the information detected, such as stigmatized health conditions. Recent studies have shown that the Internet is used more often to get health information by patients with stigmatized conditions, such as mental disorders and sexually transmitted diseases. The misuse of such data collected from the Internet by researchers can lead to stigma, discrimination, and discomfort of the subject. With no national standard, researchers and bioethicists are left to grapple with the issue of determining what situations render it permissible to turn unsuspecting individuals into a research subjects without notification or informed consent. Historically, advancements in bioethics standards have been reactionary to human subject abuses. It is vital to resist this reactionary approach to the lack of oversight in internet research and take a proactive stance to develop acceptable standard operating procedures for the use of big data sets culled from online social network websites before foreseeable abuses occur.
Privacy concerns notwithstanding, the potential societal benefit of digital epidemiology remains clear. The use of social media has the capacity to transform disease surveillance and change how healthcare workers respond to public health emergencies. As public health threats become increasingly complex, trade-offs must be made to ensure the collective benefits of population health warrant infringement on individual rights, while balancing competing ethical, health, economic, and legal concerns. Public health researchers must work together with policy makers, medical professionals, and bioethicists to develop unambiguous ethical guidelines to answer to challenges stemming from today’s technological advances and changing communications structure.
For more on this topic, visit http://ieet.org/index.php/IEET/more/hanrahan20131205.
Filed under: Bioethics, Drugs & Devices, Food and Drug Administration (FDA)
This month marks the effective date of new joint Principles for Responsible Clinical Trial Data Sharing issued by the European Federation of Pharmaceutical Industries and Manufacturers (EFPIA) and the Pharmaceutical Research and Manufacturers of America (PhRMA). The Principles commit the organizations’ members to “sharing upon request from qualified scientific and medical researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials” of approved medications.
The Principles were developed in response to growing concerns about the difficulty of evaluating manufacturers’ safety and efficacy claims without access to the underlying data from clinical trials. For example, last year, following an intensive campaign by scientists skeptical about the claimed benefits of the antiviral medication Tamiflu, the company Roche agreed to provide access to clinical study reports on all of its Tamiflu studies. Under the new Principles, companies will presumptively be expected to comply with similar requests in the future.
Yet, the Principles do not go nearly as far as some transparency advocates might have hoped. First, all requests for disclosure will be evaluated by scientific review boards made up of experts not employed by the company, who will be charged with assessing the “qualifications of the requestor and the legitimacy of the research purpose.” Second, in order to avoid “free-riding or degradation of incentives for companies to invest in biomedical research,” the statement provides that companies have the right “to refuse to share proprietary information with their competitors.”
In a draft rule circulated last summer, the European Medicines Agency proposed a more extensive system of data sharing under which de-identified research data would be published proactively, without the need for a request, as soon as a positive or negative decision on a marketing application has been made or the application has been withdrawn. The proposal would also allow for the sharing of documents containing personal information, but only if the requestor is a natural or legal person established in the European Union and agrees to enter into a data-sharing agreement containing limits on the use and disclosure of the data.
The US FDA has also entered into the discussion, although far more cautiously than its European counterpart. In 2013, it issued a request for public comments on a proposal to make available data that is not only “de-identified” but also “masked,” a term defined to mean “data with information removed that could link it to a specific product or application.” Strategies to mask data could include “making available certain data from a random sample or appropriately chosen subset of subjects, restricting the data fields made available or pooling data where possible from studies of multiple members of a product class, without identifying the specific product.”
As European and American regulators consider these proposals, it will be important to monitor how companies respond to requests for disclosure made pursuant to the voluntary EFPIA-PhRMA policy. If a voluntary disclosure system does not appear to be resulting in the free flow of scientific information, regulators may conclude that the only alternative is to implement a mandatory approach.
The Federal Circuit Decides Future Lost Earnings Award Not Authorized in Vaccine Case in Which Child Died
Filed under: Bioethics, Children's Issues, Drugs & Devices, Litigation and Liability
The National Childhood Vaccine Act of 1986 requires parties seeking relief for vaccine-related injuries to proceed through a federal vaccination claims system. If a plaintiff prevails in her suit, she (or her estate) will receive damages for pain, suffering, and expenses. Significantly, other awards include death benefits or future earnings. On October 28, 2013, the Federal Circuit answered in the negative the question of “whether the estate of a petitioner who dies prior to judgment is entitled to compensation for lost future earnings.”
Tembenis v. Secretary of Health & Human Services arose out of the epilepsy four-month-old Elias Tembenis developed following vaccination for Diptheria–Tetanus–acellular–Pertussis. His parents filed a Petition for Vaccine Compensation but while the petition was still pending, Elias died of his disorder at age seven. In 2010, a special master determined the vaccine caused Elias’ epilepsy and death.
After the special master’s determination, Elias’ estate and the Secretary of Health and Human Services agreed on damages. The estate received a $250,000 death benefit, $175,000 for actual pain and suffering and past unreimbursable expenses, and $659,955.61 in future lost earnings. The Secretary reserved the right to challenge the future lost earnings award; the special master determined that Federal Circuit precedent suggested that the estate was entitled to lost earnings. The Secretary appealed to the Claims Court which upheld the special master’s ruling.
The Secretary then appealed to the Federal Circuit. The Circuit court analyzed 42 U.S.C. § 300aa–15(a)(3)(B):
In the case of any person who has sustained a vaccine-related injury before attaining the age of 18 and whose earning capacity is or has been impaired by reason of such person’s vaccine-related injury for which compensation is to be awarded and whose vaccine-related injury is of sufficient severity to permit reasonable anticipation that such person is likely to suffer impaired earning capacity at age 18 and beyond, compensation after attaining the age of 18 for loss of earnings determined on the basis of the average gross weekly earnings of workers in the private, non-farm sector, . . .
The Federal Circuit interpreted the language to determine the statute only allows for recovery of future lost earnings. The Court acknowledged the statute does not expressly require a claimant to be alive, but it also does not expressly state an estate can recover future lost earnings of a decedent.
The Court observed that the word “impaired” implies the victim must be living. When the claimant dies before 18, no reasonable expectation exists that she would be working after 18. Thus entitlement to a future lost earnings award is dependent upon the claimant being alive. Further, the Court stated, receiving both a death benefit and a future lost earnings award would be duplicative. The Court took pains to express sympathy to the family, noting that the death benefit of $250,000 was due to be increased as it had not been amended since the statute’s enactment in 1986. However, the amount of payment can only be changed by Congress and even if it does happen, it will be of no consolation or compensation to the Tembenis family.
Filed under: Bioethics, Drugs & Devices, Global Health
At last week’s 44th Union World Conference on Lung Health in Paris, one of the main topics of discussion was the World Health Organization’s recently released 2013 Global Tuberculosis Report. On the bright side, the report confirms a steady decline in the prevalence, incidence, and mortality of TB. The world is on track to meet the 2015 target of a 50% reduction in the TB mortality rate by 2015, as compared to 1990.
Yet, despite this good news, many aspects of the report remain disturbing. Of particular concern is the limited progress achieved in diagnosing and treating multi-drug resistant (MDR) TB. WHO estimates that, worldwide, 3.6 percent of newly diagnosed TB cases and 20 percent of previously diagnosed TB cases involved drug-resistant strains. But these averages hide considerable regional variation. In some countries, MDR-TB is estimated to be present in more than 20% of new TB cases and more than half of previously diagnosed cases.
These numbers, however, are just estimates. A pervasive concern is that national detection systems fail to identify about 1 in 3 people who develop TB. The percentage of missed cases is even greater among persons with MDR-TB: WHO estimates that less than a quarter of those with MDR-TB have ever been diagnosed.
WHO has called on the international community to scale up efforts at TB detection, as the first step in a comprehensive process of global TB care. Ideally, detection will be accompanied by access to appropriate treatment, both for the benefit of the individuals who are detected and to reduce the further development of drug-resistant strains. But, unfortunately, this is not always the way things work. In 2012, of the 94,000 TB patients detected with MDR-TB, only 77,000 were started on second-line treatments. In some countries, the treatment gap was even greater; in the African region, only half of those detected with MDR-TB were provided with second-line treatment. According to WHO, ensuring that a diagnosis of MDR-TB is routinely accompanied by access to high-quality treatment “will require high-level political will and leadership and more collaboration among partners, including drug regulatory authorities, donor and technical agencies, civil society and the pharmaceutical industry.”
In the meantime, what are the ethics of diagnosing individuals with MDR-TB if treatment will not be forthcoming? From the perspective of the individual being tested, the diagnosis comes with a host of potential harms, including stigmatization, discrimination, and even detention. If access to treatment – or even humanely administered isolation – cannot be assured, individuals who are given the choice to be tested might reasonably refuse.
At a minimum, persons who are offered MDR-TB testing should be informed of the potential consequences, both positive and negative, as they should be for any other non-trivial medical procedure. If an individual refuses to undergo testing, the burden should be on those seeking to administer the tests to show that overriding the objection is necessary for legitimate public health objectives. In settings where persons who test positive for MDR-TB are not given access to treatment, such a showing could very well be impossible to make.