Clinical Trials 101: Your Guide to HIV & Research

Every clinical trial is designed to look at a specific population, so each participant is required to have certain traits (eligibility criteria) in order to take part in the study.1,2 Eligibility for study participation In order to participate in a clinical trial, a person must meet certain eligibility criteria, and these criteria are different for each study. For instance, some studies are designed to examine a specific treatment in people with a specific disease or condition, while others may only want healthy participants. The term “inclusion criteria” refers to the factors that qualify someone for a study, while “exclusion criteria” indicate factors that would prevent a person from study participation. These factors may include characteristics like age, gender, previous treatment history, other medical conditions, disease severity, etc. Study protocol Clinical trials are required to follow a very strict protocol, which is designed to protect participants and also to help produce reliable study results. Every clinical trial is led by a Principal Investigator (PI), who is typically a doctor. The protocol for the clinical trial is prepared by the PI. The study protocol will include the following: The reason for conducting the study Who is eligible to participate in the study The number of participants needed for the study The schedule of tests, procedures, or drugs and their dosages The duration of the study The information that will be collected about the participants Protecting participants of clinical trials Prior to enrolling, all participants will be provided information about the study that will help them determine whether they want to enroll or continue to participate in the study. This process, known as “informed consent”, provides information to study participants so that they understand the potential risks, benefits, and alternatives to the study. Prior to enrollment, participants will be required to sign the informed consent document. It is important for participants to understand that this is not a contract and that they have the right to withdraw from a study at any time. Institutional Review Board (IRB) All studies of a drug, biological product, or medical device regulated by the FDA, as well as any federally supported or conducted clinical studies, are required to be reviewed, approved, and monitored by an institutional review board (IRB). An IRB is responsible for making sure that the study is conducted in an ethical manner and that the rights and best interest of the participants are protected. An IRB includes physicians, researchers, and community members. Participating in a clinical trial A variety of healthcare providers may be involved in the participant’s care during a clinical trial. The assigned healthcare team will be responsible for conducting a variety of exams or tests, as well as closely monitoring the health of every participant. This monitoring may be more extensive than what one typically experiences in a standard doctor visit. Benefits and risks of participating in a clinical trial There are many potential benefits to participating in a clinical trial, but there are also risks. Participating in a clinical trial may provide access to new, efficacious treatments that are not yet available to the general public. For those who participate in a clinical trial but to not receive the new treatment being studied, they will still receive the current standard of care. Further, the health of study participants is monitored closely. In addition to benefits to the individual, participating in a clinical trial provides information to study investigators, increasing the current knowledge base around the condition. There are, of course, risks in participating in clinical trials. There may be unknown risks and side effects associated with a new drug that is being studied, and these risks are greater for the early Phase 1 and Phase 2 trials. There is also no guarantee that the new drug being studied will be better than, or even as good as the current standard of care. Unfortunately, there may also be costs associated with participating in a clinical trial, as health insurance and healthcare providers may not cover all patient care costs, so it’s important to find out about costs and coverage ahead of time. [lead_gen showIfLoggedIn="0" campaign="shortcode" source="site" title="Sign up for emails from {{site-name}}:"] Recent advances in HIV research suggest the possibility that in the near future, daily antiretroviral therapy (ART) may no longer be needed to control HIV. For years, HIV researchers have been looking to develop a cure or a vaccine for HIV. Now, using engineered immunotherapy, researchers suggest that immune cells may be able to be corralled to coax latent HIV out of cells and to destroy them. Immunotherapy, according to the National Cancer Institute, is a biological cancer treatment that marshals a person’s immune system to fight disease. Current HIV treatment ART has been a successful approach to controlling HIV. ART works by stopping HIV replicating along the HIV life cycle. Because this replication process slows down, the viral load (amount of HIV in the blood) decreases to low levels.4 The consistent and daily use of ART helps in decreasing a person's viral load to virtually undetectable levels in the blood and reduces the risk of transmission.1-4 ART has effectively reduced HIV-related complications and deaths.1,2 However, ART can not completely eliminate the virus from the body.1,2 Even with the use of ART, "HIV conceals itself and continues to reside within resting memory" CD4+ T cells (also known as T helper cells).1 Developing an HIV vaccine The fact that HIV can reside and incorporate itself into T helper cells during its latent, inactive phase is important to note. It is thought that a key to finding a cure for HIV infection is to develop a method that drives the virus out of T helper cells and then target the virus for elimination.1 Many refer to this approach as "kick and kill": kicking the virus out of hiding so that it can be effectively killed. Immunotherapy and developing a HIV vaccine Advances in immunotherapy have developed the ability to reengineer the function of certain immune cells that typically recognize and fight a different kind of virus.2 Yet, the question has been, "Which cells play host to HIV?" This is what researchers at the University of Pittsburgh School of Public Health have been looking for, so they know what immune cells to kick out.2 Using cytomegalovirus in immunotherapy Investigators there set out to examine cytomegalovirus (CMV), another virus that also has a latent characteristic and infects more than 50 percent of adults, including 95 percent of people with HIV. CMV is known to cause eye infections and other serious illnesses. It is typically controlled by a healthy immune system.1,2,4 Analysis in the lab suggests that, in some people, 1 one out of every 5 T helper cells are specific to the CMV virus.2 Researchers hypothesized that the T helper cells that are specific to fighting CMV may also make up a significant part of the latent HIV reservoir. So, researchers used immunotherapy to target the HIV and to activate CMV-specific T helper cells.2 How was this study on immunotherapy conducted? Study participants were from the Pitt Men's Study, the Pittsburgh site of the Multicenter AIDS Cohort Study (MACS). They donated substantial amounts of blood to find T cells that were latently infected with functional HIV, specifically in HIV-positive men who used ART to control the virus.2 The large volume of blood was needed because the latent T cells may appear in as few as 1 out of every 10 million cells.2 The use of dendritic cells Researchers also isolated immune cells called dendritic cells. They are described as the quarterbacks of the immune system because they “hand off the ball and dictate the plays, telling other immune cells where to go and what to fight."2 Dendritic cells are essential in the development of cancer immunotherapies. Although dendritic cells have been used to induce the immune system to kill HIV, they haven’t yet been used to kick latent HIV out of its various hiding places.2 In the most recent study published in EBioMedicine, scientists engineered "antigen-presenting type 1-polarized, monocyte-derived dendritic cells" (MDC1) that were primed in the lab to seek out and activate CMV-specific cells, with the thinking that they also may contain latent HIV.”1-4 Results of the study MDC1 was successful in the lab to use dendritic cells to incorporate CMV to both kick and kill virally infected cells after coaxing them out of their hiding places.1-4 Researchers at the University of Pittsburgh are hopeful that clinical trials based on those lab results could lead to the development of a vaccine that would keep HIV under control in people who are HIV positive and, eventually, obviate the use of daily medications.2 [lead_gen showIfLoggedIn="0" campaign="shortcode_posts" source="site"] Each year thousands of clinical trials occur. Learning about clinical trials can feel like you are learning a new language. The good news is that there are lots of resources to help support and guide decision-making before enrolling in a clinical trial. Check out 10 things to know about clinical trials and participating in trials. Clinical trials are the backbone of treatment breakthroughs Clinical trials allow researchers to understand the impact of a treatment. When it comes to treatments or drugs, clinical trials provide critical information about the drug’s safety and effectiveness. In addition, they can lead researchers down of path to develop other new treatments. Ultimately, clinical trials make a difference not just for today’s patients, but also potentially to those who’ll be diagnosed in the future. Regulatory and ethics groups oversee clinical trials All places that conduct clinical trials have strict ethical duties to participants and regulations they must adhere to. In order to ensure that the ethical and regulatory guidelines are followed, there is a team of people who are independent of the research team who are asked to review t and oversee the clinical trial. This team of people is known as an Institutional Review Board (IRB), sometimes known as Independent Ethics Committee or Ethics Review Boards. The IRB must review the research protocol before any participants can enroll in a study. Risks and benefits are different for each person Each clinical trial has different risks and benefits that are explained in the study protocol. Since each participant is different it can mean that each person may experience the risks and benefits differently. For example, it could be possible that one participant may experience a side effect that another participant does not experience. The exact risks and benefits can be difficult to predict since a component of some clinical trials is exploring the impact of a treatment. During the Informed Consent Process, a member of the research team will review the risks and benefits of the clinical trial. There are several key players involved There can be lots of different people involved in clinical trials, but there are key players to know about. Key players include the Principal Investigator (PI), who is the lead researcher leading the clinical trial. There is the trial sponsor, who is paying for research to take place. The research staff, which can include doctors, nurses, social workers or clinical research staff who will work directly with patients. Lastly, patients and their caregivers, without these key players medical advances wouldn’t be possible! Participants are able to leave a trial at anytime If you enroll in a clinical trial and then find that you are no longer able to participate, you are allowed to drop out of the trial at any stage. Trial participants do not have to provide any reason for leaving if they do not want to. If a participant decides that they no longer wish to partake in the clinical trial it is the research team’s responsibility to remove the person from the trial in a way that is safe for the participant. The health and safety of participants is the top priority One of the primary responsibilities of the research team is the care and safety of participants who have volunteered for the trial. Researchers may go by unfamiliar titles, like Principal Investigator or Study Coordinator, but they are, also, doctors, nurses, and trained research professionals. As such, they monitor participant safety and well-being. They will adjust study-related care when they feel it’s in the participant’s best interest. This may mean withdrawing a participant from a clinical trial to prevent harm. There are rules about who can and cannot participate The factors that allow an individual to participate in a clinical trial are called the inclusion criteria. The factors that disqualify an individual from participating in a clinical trial are called exclusion criteria. Inclusion and exclusion criteria are typically based on factors such as age, gender, health status, previous treatment history, and other medical conditions. There is a lot of thought and time put into the development of inclusion/exclusion criteria as these factors may have an impact on the findings of the clinical trials. The inclusion and exclusion criteria are applied to all possible study participants equally before they enroll in the study. Clinical trials occur in various settings Clinical trials could take place at a hospital, a university, a community clinic, or a doctor’s office. In addition to a variety of sites, there are a variety of researchers. Some medical professionals devote their career to conducting clinical trial research, while other research professionals conduct research for some of the time and the remaining time they are providing patient care in a healthcare setting. Evaluating the safety and efficacy of new drugs is a multi-step process When you peek inside your medicine cabinet do you ever wonder the journey that a medication underwent in order to allow it to prescribed by a doctor and land itself in your cabinet? It’s a long and thorough journey. Every potential treatment undergoes multiple phases of research, each with a different goal. In clinical trials that are studying an interventional drug, treatment, or therapy there is pre-clinical research that occurs in laboratories, usually with cells or animals. If the pre-clinical studies show promising results, the treatment team must get permission from the US Food and Drug Administration (FDA) to test in humans. The research team submits an Investigational New Drug (IND) application to the FDA and must be approved before any next steps. People have lots of different reasons why they participate There are numerous reasons to participate in a clinical trial. Some might decide to participate to gain access to new or alternative treatments. Others may join to have access to personalized and expert medical attention. Some may participate as it can provide access to medications and procedures at no cost to the participant. Some people are motivated to participate to contribute to advancing medicine. Choosing to participate in a clinical trial is an individual decision and each person may have their own personal reasons for deciding to take part in a clinical trial. [lead_gen showIfLoggedIn="0" campaign="shortcode" source="site"],Making decisions can be tough, especially when they relate to your health. One decision you may face is whether or not participating in a clinical trial is right for you. There are several types of clinical trials, and each have different goals and requirements. So, while one clinical trial may not be a good fit for you, there may be others that are. If you’re thinking about exploring clinical trial options but still aren’t sure, ask yourself some questions to determine if a clinical trial might be right for you. Willing to work with a new healthcare team during the trial? While you can still see your doctor while enrolled in a clinical trial, you will also be seeing a new group of healthcare professionals who are working on the study. Clinical trials are conducted by a group of researchers. The lead researcher for a trial is called the principal investigator (PI), who is usually a medical doctor or other healthcare professional. The research team may also include other doctors, nurses, and researchers. This research team is usually different from the healthcare team you see for your regular care. It’s important to inform your usual healthcare team of the clinical trial you are thinking of participating in and to discuss how the process will work. Willing to follow the trial protocol? The clinical trial protocol is a detailed plan of what the trial will involve. When you agree to participate in a clinical trial you will sign an informed consent document, which outlines the protocol and any tests, procedures, or appointments that are expected of you. These expectations may impact your day-to-day life. When reviewing the trial protocol be sure to note when you will need to travel to appointments and how often you may be required to have tests or procedures like blood draws or MRI scans. You may also be asked to stop taking medications you are currently on while you are in the clinical trial. Keep an up-to-date list of all medications, including over the counter medications, and show this to the clinical trial team to be sure you can continue taking them during the trial. Okay with potential unknowns? Some clinical trials are blinded, or masked, meaning that participants will not know what medication they are receiving. Some studies are double-blind studies, meaning both the participant and the research staff will not know what medications a participant is on. This is done to prevent any bias or influence and to allow the participant and researchers to measure the true effect of a drug. In blinded trials, you will be informed of all possible treatments that will be part of the trial, including no treatment (placebo). Before agreeing to participate, it is important to ask yourself if you would be okay with receiving any of the possible treatments and if you could handle not knowing which treatment you may be given. Okay with the possible risks? The research protocol and informed consent document will outline your rights as a clinical trial participant. This document will note the potential benefits of participating in a clinical trial and will also note potential risks. Clinical research is approved and monitored by an Institutional Review Board (IRB) that ensures any risks are minimal. While the research team and IRB will do everything possible to minimize risks, it cannot always be guaranteed. It is important to take note of the potential risks you may incur and decide if these possible risks are worth the benefits. Okay with the possibility of not being selected? Clinical trials are designed with certain criteria and researchers are often looking for a select group of participants with certain medical histories. These characteristics and medical histories are outlined in the trial’s inclusion and exclusion criteria. One of the main reasons people are excluded from a study is to maintain their safety. For some clinical trials, you may agree to participate and sign an informed consent document, but then be found to be ineligible for the trial after further testing. If you are not selected for a particular trial this does not mean that you cannot try and enroll in a different clinical trial. There may be other questions you have about clinical trials. You may want to talk with friends, family, and your doctor, or ask the community for their experience. Ultimately, it’s important you make a decision that you feel comfortable with. [lead_gen showIfLoggedIn="0" campaign="shortcode" source="site"] The things we know now about HIV largely comes from research, more specifically clinical trials involving people living with HIV. The success of HIV treatment today has the many people who volunteered for clinical trials to thank for the highly effective, better tolerated, and easier-to-take medications that are now available. I believe the future of our ability to respond to the needs of people living with HIV – whether it is new drugs for those just starting therapy for the first time or in desperate need of new approaches to managing side effects or most importantly, finding a cure for this disease - will depend on people continued enrollment in clinical trials. What is a clinical trial? A clinical trial is simply a medical experiment that takes place in a hospital, a clinic, or a doctor’s office setting.1 Some of these experiments are designed to test the safety and usefulness of a new drug, or perhaps to test several different kinds of drugs or treatment strategies in order to determine which one is better. Clinical trials during the HIV/AIDS pandemic At the beginning of the AIDS pandemic, many clinical trials tested drugs that treat HIV directly, and other trials tested drugs that treat or prevent the opportunistic diseases and non-AIDS-related complications. There have been trials that tested easier or more effective ways to take medications or strategies to treat side effects to medications. Trials are also underway to find a cure. I have participated in a least 12 different trials since being diagnosed with HIV. I always learn things about myself, my health, and it allows me to pay it forward. Phases I & II Phase I of a clinical trial tests test the safety of a new drug. Many also look for early markers of effectiveness.1 After Phase I, Phase II testing looks at safety and dosing information for new medications while also assessing effectiveness of treatment over several months.1 When I participated in Phase II trials, it lasted for nearly two years. Phases III & IV Phase III trials are larger and longer trials that are designed to confirm whether a treatment works and measures important safety issues.1 The data is reviewed by the Food and Drug Administration (FDA) as well as test tube and animal studies to determine if the drug will be approved.1 HIV advocacy in clinical trials In the early years of the epidemic, after activist protested and fought hard to increase the drugs tested and approved, several new drugs were granted “accelerated approval” by the FDA while the Phase III trials were still going on.2 Most of the time, the FDA requires all studies to be completed before an application for approval can be filed. That early activism lead increased access to new therapies.2 Once the studies get to Phase IV, which is the final stage, the drugs are evaluated for there effectiveness in different populations.1 My experience participating in clinical trials As I shared, throughout the years I have participated in many clinical trials. For me, participating was about making sure Black people were represented in research. I wanted to ensure the physiology of Black people was considered in determining if the drugs and treatments were effective for people of color. I still participate in clinical trials. Not for new drugs, but for research about the brain, heart, and even issues like anal cancer. I have also considered my participation in clinical trials as one additional way I can support the HIV community. [lead_gen showIfLoggedIn="0" campaign="shortcode_posts" source="site"] ,What is a clinical trial? A clinical trial is a research study that is conducted to determine whether a specific medical intervention, such as a treatment, device, procedure, or change in behavior is safe and effective in humans. A clinical trial may be designed to compare a new treatment to one that is already available, to a placebo (contains no active ingredients), or to no intervention. Further, some clinical trials compare interventions that are already available, to each other.1,2 The process of investigating the safety and efficacy of a specific intervention is complex, and clinical trials are actually one of the final stages of that investigation. A new intervention will first be examined in a laboratory, and if data for that intervention look promising, the next step could involve testing that intervention on animals. Of course, even if that intervention seems promising in animals, it may or may not have similar results in humans. Therefore testing a new intervention in humans is necessary. This testing is done in multiple phases, which are defined by the Food and Drug Administration (FDA). Clinical trial phases Phase 0 The Phase 0 study is a relatively new designation. They are exploratory in nature and involve very limited human exposure to the drug. They are also known as human microdosing studies, with a goal of speeding up the process of development for promising drugs by examining the pharmacokinetics of the drug in a very small number of patients (10-15). Phase 1 Phase 1 studies are usually conducted with a small group of healthy volunteers (usually between 20-100 people) and examine the safety of the drug. The goal is to evaluate the drug’s most frequent and serious adverse events. Often times a secondary goal will be to look at how the body processes the drug (metabolism and secretion). Phase 2 Phase 2 studies gather preliminary data on the efficacy of a drug in people who have a certain disease or condition, and these studies include a larger number of patients (typically 100-300). Study participants receiving the drug may be compared with similar participants receiving a different treatment, which is usually an inactive substance (called a placebo) or a different drug. The safety of the new drug continues to be examined. Phase 3 Phase 3 studies gather more information about safety and effectiveness of a drug. Phase 3 studies include a much larger group of participants (often 1000-2000), with the goal of definitively assessing how efficacious a treatment is. It is typical for there be at least two successful Phase 3 trials that demonstrate the safety and efficacy of a drug to gain approval from the FDA. Phase 4 Phase 4 studies are conducted after FDA has approved a drug for marketing. These studies gather additional information about a drug’s safety, efficacy, or optimal use. Funding for clinical trials Clinical studies can be funded by a variety of sources, including pharmaceutical companies, academic medical centers, voluntary groups, federal agencies such as the National Institutes of Health, the U.S. Department of Defense, and the U.S. Department of Veterans Affairs. Physicians, health care providers, and other individuals can also sponsor clinical research. Clinical trial locations Clinical trials take place in a variety of settings, including hospitals, doctors’ offices, universities, and community clinics. Often times, a clinical trial will have multiple sites (locations). This is determined by who is conducting the trial. [lead_gen showIfLoggedIn="0" campaign="shortcode" source="site" title="Sign up for emails from {{site-name}}:"]

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