November 2, 2020
by Rachel Spahnn

Now that we are in the midst of a pandemic, our news feeds are swarming with articles about operation WARP speed, the vaccine approval process, remdesivir, hydroxychloroquine, and more recently, dexamethasone. Industry lingo is thrown around without much consideration for the reader, who is probably unfamiliar with the clinical trial process and hearing these terms for the first time.

Several vaccine candidates have been developed in record time as a result of the immense investment in resources and recent technological advances in vaccine development and manufacturing. Limited distribution may begin by December.  In the past, most vaccines took approximately 10 years and the fastest a vaccine has been developed to date was for mumps which took 5 years. Clinical trials often took years to get enough data because the incidence of a disease is relatively low, but clinical trials in a pandemic can progress much more rapidly because we have a much higher incidence of disease.

The rush to develop a vaccine is hotly debated in the media, but there is a separate effort being undertaken by scientists and medical professionals globally - the quest for a treatment that will help keep patients who have already contracted COVID alive and relieve their symptoms effectively. Ideally, an existing drug already FDA approved to treat other conditions will also work to combat the effects of this virus, substantially reducing the time to approval for widespread use. So far, broad-spectrum antiviral drug Remdesivir has been approved for treatment of inpatients with confirmed COVID-19 diagnoses, and a steroid called dexamethasone, which targets inflammation, has shown early promise for critically ill patients.

The race is on to find a cure. Hundreds of treatment trials are underway.

If you are feeling overwhelmed with the amount of information flooding your inbox about potential vaccines and treatments for COVID-19, you’re not alone. These 10 facts about the drug development process in the US will help you understand what you are reading, and form your own opinion about how this issue is being handled.

1. Study protocols must be developed and approved by the Institutional Review Board (IRB) and FDA prior to beginning a study. A protocol is binding and communicates to the regulatory authorities and study teams alike the methodology that will be used to conduct the research. Protocols take months to develop, and recruitment timelines rarely go according to plan due to inevitable regulatory hangups.

2. The scientists running the trials, known as investigators, must get approval from the FDA to begin administering the experimental substance to human study participants. This can take many months.

   Before a new therapeutic or vaccine can be administered to human subjects, investigators must submit what is known as an investigational new drug (IND) application to the FDA. An IND application typically requires an array of supporting documentation, such as a draft protocol, informed consent form, manufacturing information, etc. Once submitted to the FDA, the study team must allow a 30-day waiting period to elapse prior to enrolling subjects in the study. If no communications are received by the FDA in regards to the application within 30 days, then the study may resume.

3. The drug (and vaccine) development process follows 4 distinct, lengthy steps, from the theoretical development of a substance, to animal testing, to human testing, to regulatory review, which all typically takes 10 years in total.

   Why does this process take so long? Between phases, scientists must analyze the data collected to determine the safety and effectiveness of the drug or vaccine being tested in order to justify continuing the trial. The research continues only if testing the substance on human subjects is consistently found to be potentially beneficial to society down the line.

4. The study team must submit all significant protocol changes - which include dosage adjustments, additional lab tests, and changes to data collection methods - manufacturing changes, and serious adverse events  to the FDA for review, along with all relevant documentation.

   More often than not, various aspects of study conduct will be changed by the investigator(s) over the course of a study, as the study team becomes more familiar with the drug being tested and its expected and unexpected effects. Each change to a process outlined in the IND application must be submitted to the FDA as well. FDA submissions can be time consuming to compile. The responsible party must assemble the proper documentation and obtain the required signatures. The study team cannot implement any changes until they have been approved by the presiding IRB and submitted to the FDA.

5. Study teams must keep detailed records and take measures to ensure that personal health information (PHI) is kept confidential as per HIPAA.

   This often involves masking identifiers such as name and date of birth with numbers, and keeping data stored in a compliant manner, either on an encrypted or password-protected hard drive or server, or in a locked file cabinet in the lab. Data management can be highly time consuming, and is subject to audit, either by institutional entities or by the FDA itself.

6. All participants must be screened for eligibility before they can be considered. Investigators must review and sign off on each participant’s eligibility prior to enrollment, and many investigators are involved in multiple studies at any given time.

7. Investigators often fail to build enough project management support into their grant proposals, leading to understaffed, backlogged study sites. If it becomes necessary to hire additional staff, this can take months, depending on the site.

8. Vaccine trials require extra care and attention to safety, considering that it is intended to be administered to healthy people. The benefits of a viable vaccine to a healthy person must outweigh the risks. COVID-19 Vaccine Tracker

9. The FDA offers an Emergency Use Authorization (EUA) option for certain situations:

   “Under section 564 of the Federal Food, Drug, and Cosmetic Act (FD&C Act), the FDA Commissioner may allow unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by CBRN threat agents when there are no adequate, approved, and available alternatives.”
   It is worth noting that drugs granted EUA are subject to ongoing review. For example, the EUA granted to hydroxychloroquine and chloroquine sulfate on March 28, 2020 was revoked on June 15, 2020:
   “...FDA has determined that CQ and HCQ are unlikely to be effective in treating COVID-19 for the authorized uses in the EUA. Additionally, in light of ongoing serious cardiac adverse events and other serious side effects, the known and potential benefits of CQ and HCQ no longer outweigh the known and potential risks for the authorized use.”

10. There are currently 11 potential vaccines being tested in the United States, 4 of which are in Phase 3 of the process, which means they are being tested on a large scale. If any of the candidates successfully complete Phase 3, meaning that they can prove using data collected and analyzed by their team that the vaccine is safe and effective, then they must apply for a Biologics License through the FDA. The FDA may also conduct its own testing of the vaccine prior to granting approval.

Nobody can say when or even whether a viable vaccine or treatment will be approved or ready for use. Even though there are vaccine candidates in the later phases of the process, there is no guarantee that any of those will be proven to be safe and effective. For the time being, conducting ourselves according to CDC guidelines will help keep us and those around us safe from harm. Be safe out there!