New discoveries of therapies and drug mechanisms are not always the daily news headline, but today ethical guidelines exist to continue to keep a standard of the production of any new medication or treatment. However, the history of clinical research has not always been so ethical. For instance, the PHS Syphilis Study in Tuskegee, AL and the Willowbrook Hepatitis Experiments, are only two of many notorious examples of horrifically unethical clinical trials. The purpose of this article is to bring light into the role of the Institutional Review Boards (IRB) in relationship to on ongoing  clinical trials today to ensure safety for human participants.

In 1974, Richard Nixon passed the National Research Act. This act was created to ensure excellence of biomedical and behavioral research within the United States. These guidelines within the National Research Act emphasized a respect for autonomy, beneficence, and justice for research participants. As a result, the Institutional Review Boards (IRB) was formalized, for all DHHS-funded research, as a Committee. This committee would reside either within the research institution or be external (e.g., commercial IRB’s); and would be an ethical review board designated to protect the rights and well-being of human research participants.

The IRB must be independent from the institution for which it reviews research to avoid any inherent bias within the study, though it is often made up of faculty and staff of the institution. The IRB functions to review and monitor research involving any human subjects. This board has the power to approve, enforce any change, or reject research of a clinical trial. Moreover, patient safety is a priority in clinical trials and the IRB plays a fundamental role in this. Thus, the board will review the protocols and progress throughout the study. The main goal of the IRB is to confirm that the right steps are taken to protect the welfare and the rights of participants. The IRB also operates to verify the integrity and quality of the data being collected. IRB is also required by the Federal Drug Administration (FDA) regulations and may perform audits of the clinical trial study records.

Prior to a patient being recruited for a clinical trial, there must be both legal and ethical steps to ensure the patient fully understands what their part in the clinical trial will entail. The IRB will review documentation presented to participants to ensure procedures, risks, and benefits are discussed. This process is known as informed consent. Informed consent consists of verbal and written documentation that confirms the participants acknowledge and understand their part in the clinical trial in its entirety. A signed informed consent document is part of the process for ensuring that the institution is compliant. This process is designed to help patients thoroughly understand what to expect as well as the risks and benefits of participating. It’s important to note that the informed consent form is only one part of the informed consent process; there must also be an ongoing process, including updating the participant of any new information throughout the study.

In conclusion, while some of the history of clinical trials is disheartening, today the IRB continues to provide advocacy and protection for any participant within in a clinical trial and remains to be an integral component to the welfare and safety of human participants within clinical trials.

Resources:

The History and Role of Institutional Review Boards: A Useful Tension:  https://journalofethics.ama-assn.org/article/history-and-role-institutional-review-boards-useful-tension/2009-04

Being in a Clinical Trial: https://www.cancer.org/treatment/treatments-and-side-effects/clinical-trials/what-you-need-to-know/what-does-a-clinical-trial-involve.html

Clinical Trials: What Patients Need to Know: https://www.fda.gov/patients/clinical-trials-what-patients-need-know

Thinking about joining a clinical trial? Here’s what you need to know:  https://www.health.harvard.edu/blog/thinking-joining-clinical-trial-heres-need-know-2016090110187

Who owns the rights to a new innovation described in a research paper? If a patent is in place, the answer is simple: the owner. Generally, the lengthy, and confidential, peer-review process means that authors of unpublished work have ample time to submit an invention disclosure and to have their technology transfer office review and if necessary, file a patent, ensuring that any new invention is protected prior to any public disclosure. However, the rise of “preprint” services, which allow authors to publish preliminary findings ahead of peer-review, has complicated this process. Preprints can severely hamper the ability of authors and their universities to patent new inventions described in their work if appropriate steps are not taken prior to public disclosure. Whenever possible, university researchers should consult with their technology transfer office prior to submission of manuscripts to a preprint server to ensure that any patentable inventions are adequately protected.

Scientific manuscripts accepted for publication as preprints have become increasingly common in the past decade, as searchable databases such as bioRvix and MedRxiv allow authors to publish their work online with relative ease. Many authors choose to publish preprints because their findings are negative or contradictory and have a low chance of being published in a journal. Others may publish preprints to obtain quick and wide feedback for work that is concurrently receiving peer-review. Preprints often gain substantial exposure, especially for the many studies concerning research related to COVID-19. In fact, many scientific studies cited in the media are preprints awaiting peer-review.

Preprints certainly have their place and help to enable rapid distribution of scientific results and can help give an article beneficial attention, but authors should be aware that they also complicate the process for protecting new, and potentially valuable innovations that may be described in a paper. While traditional peer-review can often take months to complete, the preprint services often compress this process into days or weeks, meaning articles may be published before authors or inventors and their respective universities have had a chance to evaluate the invention and to file a patent application. Under most countries’ patent laws, any invention that is disclosed publicly before a patent application is filed may be considered “prior art,” and therefore may be ineligible for patent protection. It is therefore critical that authors and innovators work with their university to file the appropriate patent applications for their work before submitting manuscripts to preprint services to protect any potentially valuable intellectual property.

Researchers seeking to commercially market new innovations should be aware of the consequences of foregoing intellectual property rights by publishing early. Without adequate protection, it is unlikely that a commercial partner will be able to further develop and eventually distribute products based on the innovation. Patents provide an incentive to commercial partners to invest in new inventions, and without some guarantee of exclusivity, industry partners are likely unable to move promising technology to market. The university technology transfer office is accustomed to working with researchers (even on tight timelines) to ensure that new innovation can be successfully protected and commercialized while balancing the need for rapid publication.

University researchers should contact the tech transfer office early in the study, especially if the resulting data look promising. “We’re always happy to work with our researchers on filing a patent before a public disclosure, and the earlier we can be involved, the better protection we can secure for our intellectual property,” notes licensing associate John Nicosia. Preprint manuscripts often generate positive attention for the research within the scientific community, the greater public, and those business development professionals looking for the next big discovery. However, researchers seeking to patent new innovations arising from their work must be aware of potential pitfalls before submitting a manuscript for preprint publication.

PHI stands for Protected Health Information and encompasses all information acquired during health care services that could potentially be used to identify an individual. PHI does not only include medical records, but also communications between medical personnel regarding treatment, billing information and health insurance reports.

For information to be formally considered PHI under the law, it must be created, received, stored, or transmitted by HIPAA-covered entities. Under the Health Insurance Portability and Accountability Act (HIPAA), covered entities are limited in the types of PHI they can collect from individuals, share with other organizations or use in marketing. HIPAA-covered entities include healthcare providers, insurance providers, healthcare clearinghouses and their business associates who have access to PHI. These entities must implement guidelines to protect against the unauthorized disclosure or destruction of PHI as required by the HIPAA Privacy Rule.

PHI is also a commodity and is valuable to clinical and scientific researchers when anonymized, as it can be used observational studies. However, PHI can be very attractive for hackers, since it can be illegally sold online or targeted as part of a ransomware attack.

PHI does not include education record information or data used by healthcare entities in their role as employers. In total, there are 18 unique identifiers considered to be PHI:  (For more information on the 18 identifiers visit: https://www.hipaajournal.com/what-does-phi-stand-for/)

• Names
• Geographic data
• All elements of dates
• Telephone numbers
• FAX numbers
• Email Addresses
• Social Security Numbers
• Medical record Numbers
• Health plan beneficiary numbers
• Account numbers
• Certificate/ license numbers
• Vehicle identifies and serious numbers including license plates
• Device identifiers and serial numbers
• Web URLs
• Internet protocol addresses
• Biometric identifiers (e.g. retinal scan, fingerprints)
• Full face photos and comparable images
• Any unique identifying number, characteristic, or code

As medical care becomes increasingly sophisticated, the successful transfer and utilization of patient records is critical for providing the best outcomes. The Fast Healthcare Interoperability Resource (FHIR), developed by the nonprofit group Health Level 7 International (HL7), is the latest standard for such data. FHIR seeks to transform the way patient data is used by giving everyone from doctors to developers the opportunity to view and build on it in unprecedented ways.

Before FHIR, standards for sharing patient data could roughly be compared to PDFs. Health care providers receiving a report from another doctor could see the doctor’s notation, but generally not the underlying data that the doctor collected. Even if the provider was able to get access to that data, no protocol existed for filtering it or interacting with it. This informational gap severely hampered the ability of health care providers to collaborate in providing treatment.

FHIR, which was first released in 2011, uphanded this dynamic. Rather than providing static printouts, FHIR relies on data elements called “resources,” which are unique identifiers for medical information. Through combinations of these resources, FHIR expresses medical data, allowing health care providers to see and interact with the information. FHIR can be roughly compared to a URL, generating a dynamic form of patient records more akin to a webpage than a PDF.

The interoperability of FHIR leaves open many possibilities for future uses. The rise of wearable devices and Internet of Things technology means that there is more medical data floating around than ever before. Using FHIR, developers can create tools that allow health care providers and patients to utilize this data in innovative ways. For example, using the iOS app Apple Health, patients can now download their FHIR records. The app can keep those records up-to-date and organizes and presents them in a more user-friendly way, simplifying a previously confusing process. The resource-based nature of FHIR allows these records to be automatically updated every time new information is added. These discrete resources are then compiled for patient viewing on the Apple Health app, generating a readable report.

Doctors can also use Apple Health to view data from wearable devices such as the Apple Watch. With patient consent, doctors can incorporate heart rate data from such devices into medical records to help detect heart conditions and tailor treatment. In addition to Apple, Google, Microsoft, and Amazon are also working on applications that incorporate FHIR. FHIR apps are available on two primary marketplaces, run by software companies EPIC Systems and Cerner. Analogous to the iOS App Store or Google Play Store for smartphones, these two marketplaces allow developers to sell FHIR applications directly to consumers and healthcare professionals.

Doctors are also seeing other benefits from the integration that FHIR provides. A prime example is in the notation and documentation of medical records, which previously was a cumbersome process involving the use of dictation devices and apps to upload records to desktop-based records systems. Now, FHIR-based apps are beginning to emerge that can upload medical records quickly and seamlessly. The Nuance Surgical CAPD allows surgeons to create fully operative notes in less than 90 seconds. Doctors can dictate notes and capture images directly from their smartphones and upload them securely to a patient’s medical records.

One primary concern of FHIR developers is protecting patient privacy. While the open-source nature of FHIR allows increased collaboration and interoperability, it leaves open the possibility that third-party apps may not adequately protect sensitive medical data. In December 2018, EPIC instituted a three-month halt on applications by new developers to its FHIR “App Orchard.” EPIC later reopened enrollments with more stringent requirements for HIPAA compliance and security. With these concerns in mind, universities and medical providers have begun to give seals of approval to select FHIR applications that protect privacy. For example, Emory’s FHIR Advisory Committee gives formalized endorsements to apps that meet several criteria, one of which is protecting patient privacy.

Everyone who examines medical records, from hospital systems, to individual doctors, to insurance companies, will find FHIR helpful in creating a seamless patient experience and improving standards of care. FHIR apps are already serving innovate roles, from helping doctors manage medication dosage to streamlining directives for end of life care. FHIR will serve as a key building block of the medical records market for years to come, as the basis for innovative methods of sharing and analyzing medical data.

Any time a new drug appears on the market, the final product is a result of years of research and testing. The time from conception to FDA approval for medications takes 12 years on average. An important and time-consuming aspect of this process are clinical trials. By testing a drug on gradually increasing numbers of patients and volunteers, researchers are able verify that it is both safe and effective in treating the disease or condition. Only when the first three steps of this process are complete can the drug be approved and commercially distributed.

Phase 1 is the shortest of the three phases and involves the smallest sample size. This phase is the first time a new drug is tested on humans and establishes the product’s safety. During Phase 1, the drug is given to 20 to 50 volunteers. Generally, this process takes several months. By examining subjects over this period, researchers are able to determine the appropriate dosage, observe side effects, and glean limited information about the drug’s effectiveness. These data are taken into consideration as researchers plan for Phase 2, which approximately 70% of drugs move onto.

Phase 2 gives researchers a clearer picture of a drug’s efficacy and safety. With preliminary safety data available, testing can be expanded to groups of up to several hundred patients. While these samples typically aren’t large enough to fully test a drug’s effectiveness, the results provide further insight into whether it is safe. Phase 2 trials last several months to two years. They are critical in winnowing out unsafe or unsuccessful drugs, with only approximately 33% of drugs proceeding to Phase 3.

The longest and most complex step of clinical trials is Phase 3, which involves 30 to 300 patients and takes 1 to 4 years. Phase 3 answers the most critical question for any drug: whether it provides the beneficial treatment it was designed to. Researchers test this by randomizing the study’s participants. Half of patients receive the experimental drug, while the other half are given a placebo. Studies are usually double-blind, which means neither the participant nor the researchers know who is in which group. Results from the two groups are then compared to determine the effectiveness of the drug. Phase 3 also provides additional safety data by sometimes revealing side effects that went undetected in smaller sample groups. Approximately 25 to 30% of drugs complete this phase and are ready for FDA approval.

Once drugs are FDA approved and commercially available, further testing continues in Phase 4 clinical trials. Although the drug has already been approved, Phase 4 allows for analysis of any long-term effects. Additionally, Phase 4 allows for more organic testing among groups that may not have been studied due to the controlled nature of previous phases, such as those simultaneously taking other drugs. Sometimes, drugs are banned from use by the FDA after harmful side effects emerge during Phase 4.

Clinical trials are a time-consuming, expensive, and selective process. Drugs that make it through and are FDA approved have an average cost of $41,117 per patient just for clinical trials. The federal government has created a database that is home to information about both privately and publicly funded clinical studies around the world. However, clinical trials remain the most comprehensive method available to ensure that every drug marketed in the U.S. is both safe and effective. Doctors and patients can have confidence knowing the drugs they prescribe, and use, have been put to this test and passed.

Countless patients, clinicians, and caregivers have relied on medical devices over the years for health needs. But bringing a medical device to market in the United States is no easy task. It involves not just building the device and testing it, but also obtaining regulatory approval from the Food and Drug Administration (FDA) prior to marketing the device. What follows is a simplified overview of the regulatory process.

Medical devices are broadly grouped into three classes based on the potential risk and intended use: Class I, II, and III. Class I is the lowest risk and includes things people may not often think of as medical devices like tongue depressors and latex gloves. 47% of all devices fall into Class I. Class II devices (43% of all devices) include infusion pumps, surgical needles, and powered wheelchairs. Class III devices carry the most risk and are the least prevalent class of all devices (10%). The FDA defines these devices as “those that support or sustain human life, are of substantial importance in preventing impairment of human health, or which present a potential, unreasonable risk of illness or injury.” Examples include implantable pacemakers and replacement heart valves. Devices in each of these classes may be subject to one of several pre-submission FDA regulatory pathways. Two of the most common are 510(k) and PMA.

510(k), otherwise known as pre-market notification or PMN, is the simpler and less costly route, and it is for lower risk devices. The name comes from it being in Section 510, paragraph “k” of the Federal Food, Drug, and Cosmetics Act. All Class I, II, and III devices that do not require PMA must have a 510(k) submission, unless they are subject to exemption. Most Class I devices and some Class II devices are exempt from 510(k) requirements. 510(k) notification involves identification of a legally marketed “predicate device” that is substantially equivalent to your device. Once substantial equivalence has been shown and confirmed by the FDA, the device can be marketed in the US. The time from 510(k) submission to when you hear back from the FDA is typically 90 days or less.

PMA, short for pre-market approval, is required for all Class III medical devices (unless they were on the market prior to 1976, when the FDA started regulating medical devices). It is a substantially more involved process (time and money), in some ways similar to the clinical trials process mandated for new drugs to go to market. PMA requires demonstrating the device is safe and effective for its intended use, not just that it is substantially equivalent to an existing device. The application packet requires extensive laboratory and clinical studies. Beyond the cost of developing the device, one must also factor in the cost of FDA submission. As of the time this blog was written, the standard fee for submitting a PMA application is $322,147 ($80,537 for a small business), versus $10,953 ($2,738 for a small business).

If you are trying to determine which category your device falls under, you should start by checking out the FDA’s guidelines for determining that on their website here