What Are Clinical Trials?

Clinical studies are research studies performed in people as a way to understand new medicines, devices, procedures, and treatments. The objective is to determine if they are safe and effective. Such studies are sometimes also called “Clinical trials”. Often a clinical study is performed to evaluate if a new medication or treatment method is more or equally effective and/or has fewer or less harmful side effects than the existing treatment.

A clinical study performed in the United States must be submitted to the U.S. Food and Drug Administration (FDA) and approved by the Institutional Review Board (IRB) of the hospital or center where the study is being performed. Both must affirm the study to be ethical, as safe as possible, and valuable to patients and science in the future. Every patient who is entered into a study must sign an “informed consent” (permission) form to be entered into the study after being given a thorough explanation of the study, both verbally and in writing. Studies performed in minors must have parents or guardians give their approval.

What Are the Phases of Clinical Research?

Clinical research includes four phases to test a potential treatment’s effectiveness, find the appropriate dosage (or amount of the drug that works best), and to understand the potential side effects that people might experience when taking the experimental treatment.

Before even starting a Phase I first-in-human study, researchers must conduct “preclinical studies” to see if there is a potential benefit of the new treatment for a specific disease by testing the treatment in animals (or other models). These preclinical studies must show the experimental treatment at doses to be tested in humans has a positive benefit-risk assessment to allow for its use in the experimental setting of a clinical study. The FDA must agree with the preclinical study results to move forward.  

  1. Phase I Studies test an experimental medication or treatment on a small group of often healthy people (generally 20 to 80) and preferably with an equal number of men and woman representing various major races, if possible, to judge the drug’s safety, to understand any major side effects and to estimate the correct drug dosage (amount that works best) and the ideal frequency of use.
  2. Phase II Studies use more people (100 to 300). While the emphasis in Phase I is on safety, the emphasis in Phase II is on effectiveness (how well it works) along with safety. This phase aims to obtain preliminary data (information) on whether the drug works in patients who have a specific disease and often includes further evaluation of doses for future study. These studies also continue to study safety, including short-term side effects. It is preferred that men and women are equally represented and that all races be adequately represented.
  3. Phase III Studies gather more information about safety and effectiveness of the medication or treatment in a much larger population. Importantly, the Phase III study compares the new drug against the standard of care from an efficacy and safety perspective. It may also be compared to use of no other drug or a “placebo” (a pill that looks the same but has no drug inside it). The patients are randomized to get the experimental treatment to avoid bias in patient selection. This decision may be hidden (“blind”) from the investigator or known to the investigator (“open”). The study and control patients should have equal representations of race, gender, age, and defined disease conditions. Some studies may evaluate different dosages of the drug or use the drug in combination with other drugs. The number of people participating in this phase is defined upfront to deliver statistically valid data and reach a well-defined conclusion. The number of patients in Phase III trials range from several hundred to thousands of subjects. To give the experimental drug final approval, the FDA must agree that the drug is efficacious and has an acceptable safety profile. [ML1] In addition, the study must be performed precisely as described and the result recorded accurately.
  • Phase IV Studies take place after the FDA approves the use of the drug. The purpose is to assure the safety of the drug in a larger number of patients over a longer period of time. A drug’s effectiveness and safety are monitored in large, diverse populations. Sometimes, the side effects of a drug may not become clear until more people have taken it for a while. In addition, Phase IV studies are often used to collect additional efficacy and safety data in broader sets of patient populations.

Why Participate in a Clinical Study?

Some people join a study because the treatments they have tried for their health problem did not work or there is no treatment for their health problem. Some studies are designed to help find better ways to prevent, treat, or manage a disease. For example, a goal can include finding a treatment with fewer side effects or an improved quality of life.

Many people say participating in a clinical study is a way to play a more active role in their own health care. Other people say they want to help researchers learn more about certain health problems. Whatever the motivation, when people choose to participate in a clinical study, they become a partner in scientific discovery. And this contribution can help future generations lead healthier lives. Major medical breakthroughs could not happen without the generosity of clinical study participants.

How Do You Find and Enroll into a Clinical Study?

Individuals can find information about ongoing clinical studies through their doctors or health care providers. They can also search online or sign up for a matching service to get connected to a study of the treatment of their disease in the area where they live. Studies are often conducted at more than one research center and may require the patient to live / stay within a certain distance from the center where the study is conducted.

To enroll into a clinical study, the patient must contact the clinical study investigator or study coordinator to schedule a screening appointment to see if he/she qualifies. At times, study teams may contact potential patients to invite them for a visit to see if they are interested in participating in the study. If the patient is interested in participating, they will participate in an initial study visit to explain the protocol (what will happen in the study), obtain patient consent, and recruit the patient. There are certain specific inclusion / exclusion criteria for each patient.  Age, stage of disease, gender, genetic profile, family history, need for other drugs that may interfere with the tested drug, and whether or not the patient has a study partner who can accompany him/her to future visits are examples of inclusion / exclusion criteria. Exclusion criteria might also include specific high risk health conditions. Importantly, a patient may only participate in one research study at a time.

The screening process includes both a thorough history (what has happened to a patient with their health over their entire life) and a comprehensive physical examination, as well as cognitive (mental) tests. Often, one first completes a questionnaire or a survey online, which is followed by a phone call with the study coordinator. Then, an in-person screening visit at the study site with an investigator and/or the study coordinator might include a physical examination and review of candidate’s medical history. Laboratory testing (e.g. blood tests, urine test) and/or special diagnostic testing (e.g. x-ray, MRI, CT scan) may also be required.

Before any laboratory/diagnostic tests are performed or any screening documents are completed, the candidate must review and sign a participant information sheet and an informed consent form. This document is not a contract; it represents an agreement to participate in the study and an understanding of what it will involve. For example, it will outline the purpose of the study, what participation is required of the candidate (how long it lasts, initial visits, follow-ups procedures), risks / benefits, compensation, confidentiality, and more). You may withdraw your consent and leave the study at any time.

What Happens to You During a Clinical Study?

If accepted into the study, you will then be randomly assigned (“blindly” or “knowingly”) to the treatment group or to the control group. The control group does not receive the experimental treatment, which permits the study staff to compare the results in patients who receive the experimental item versus those who do not receive the medication being tested. The control group may receive a placebo (inactive pill or injection), or the standard of care treatments generally administered to the patients with the disease being studied. Some studies are partially/single-blinded, meaning that either you or the study staff do not know which group you are in, or double-blinded, meaning both you and the study staff do not know which group you are in. This helps remove any biases when analyzing the results of the treatment at the conclusion of the study.

Throughout the duration of the study, the candidate must adhere to the study procedures and protocols, and report any issues, deviations, or concerns to researchers (these are known as adverse events and adverse reactions). You may be asked to visit the research site at regularly scheduled times to receive treatment and/or for new cognitive (mental), physical, or other evaluations and discussions with the study staff. At these visits, the research team collects information about effects of the treatment and about your safety and well-being. You continue to see your regular physician for usual health care throughout the study.

What Happens When a Clinical Study Ends?

Once a clinical study has ended, the researchers will collect and analyze the data to determine what subsequent steps are needed as a result of the findings in the study. The analysis of the results are generally posted on the website clinicaltrials.gov within 12 months of the completion of the study, at which time a press release may be issued announcing the results. In most cases, the findings will also be presented at a scientific meeting and published in a scientific journal. The study findings, together with the protocol and other documents, will be filed with the FDA for their review with the goal of having the new drug (or its new use) approved and licensed for use. Upon approval, the drug can be launched and promoted. As a participant, the candidate should be informed before entering the study about whether he or she will continue to receive the study treatment if appropriate and desirable after the study closes (ends), and how to be kept informed about the results of the study. 

This article is made possible by the support of ITB-MED LLC. 

Glossary of Definitions

Adverse event: Any health problem that happens during the study.

Adverse reaction: A health problem that happens during the study and is possibly caused by the study treatment.

Assessment: Information that is collected and analyzed from a study participant.

Clinical benefit: A health change that researchers measure to find out if the study treatment helps the study participants.

Clinical research: A controlled way to study health and illness in people.

Clinical study (trial): A way to study new drugs, devices and treatments to see if they are safe and work in people.

Confidentiality: Protecting personal information from people who should not have access.

Consent form: A document used to explain the details of the research study.

Control group: People in a study who do not have the condition being studied.

Data: Information collected from or about people taking part in a research study.

Discontinue: To stop a study treatment or stop being a participant in the study.

Double-blind study: A study that is set up so that participants do not know which study treatment they are getting, and researchers do not know either.

Efficacy: How well a study treatment works in the study.

Eligibility criteria: The reasons a person can be included in, or excluded from, a study.

Endpoint: A measure of the expected effect of the study treatment (for example, lower blood pressure or reduced sleeplessness).

Enroll: Agree to join a study as a study participant.

Exclusion criteria: A list of reasons a person cannot be included in a study.

Inclusion criteria: A list of requirements a person must meet to take part in a study.

Informed consent: The process of learning and discussing the details of a research study before deciding whether to take part.

Institutional review board (IRB): A team of people who review studies to protect the rights and welfare of study participants.

Investigator: A person who leads a research study.

Phase: A step in the overall clinical research process to test a new drug or treatment.

Placebo:  A substance or treatment which is designed to have no therapeutic value, a so called “sugar pill”.

Preclinical study: A study to test a treatment in the lab or in animals before testing it in people.

Protocol: A complete description of the research plan and procedures.

Randomization: A way to use chance to place study participants into different study treatment groups.

Side effect: A health problem that is likely caused by an approved treatment.

Single-blind study: A study that is set up so that participants do not know which study treatment they are getting.

Standard of care: Treatment usually given to patients for an illness.

Study design: The way a study is set up to answer the study question.

Study participant: A person who joins a research study.

Study population: All the participants in a study.

Withdraw: To stop being a participant in a study.

Sources and more information:

The field of transplant medicine is undergoing transformative changes that are set to significantly improve the management and outcomes of organ transplantation. These advancements are very important for transplant recipients, offering them the potential for a better quality of life, longer organ survival with better function as well as fewer short and long-term complications.

Transplant Medications

In this field, scientists are working hard to find alternatives to calcineurin inhibitors (CNIs). CNIs are the main drugs used to stop the body from rejecting transplanted organs. However, they can be nephrotoxic (damaging to the kidneys) which not only affects kidney transplant patients but also those who have received heart, lung, or liver transplants. CNIs can cause high blood pressure, kidney problems, memory issues, and new cases of diabetes. Researchers want to find new treatments that are safer and just as effective as CNIs. This is important because it could help people live healthier, longer lives after their transplants.

[ML1] Another medicine available today, belatacept[LB2] , helps stop the immune system from attacking the new organ by blocking the activation of certain immune cells in your body. There are other new drugs in clinical trials that target parts of the immune cells to modify their activity. With any luck in years to come, we may have additional medicines that doctors can prescribe for their patients.

More Organs

While over 46,000 transplants were performed in 2023, there are around 100,000 people on the waitlist. The primary reason someone cannot get a transplant is the limited number of kidneys available. Someone either has to die and donate an organ, or someone needs to voluntarily give a kidney to a recipient. The system needs more organs, and despite great efforts to educate people on the value of kidney donation, we still do not have enough organs. More than 17 people die each day on the waitlist, as they cannot wait any longer. We need more organs. [REF]

Scientists are turning to new sources of organs, such as xenotransplantation, to address this urgent demand. Xenotransplantation is the transplantation of animal organs into humans. It has gained traction in recent years through advances in gene editing. Scientists can change pigs to make their organs more like human organs by adding some human genes and taking away some pig genes that humans react badly to. Pigs are the favored xenograft (organ) donors because their kidneys, heart, lung, and pancreas function similarly to those of humans. Their livers do not. Pigs have big litters, usually six or more, and their pregnancies only last 60-65 days, so many pigs can be born in a short time.

Alongside xenotransplantation, advancements in tissue engineering and regenerative medicine will [LB3] enable the creation of new organs from a recipient’s own cells. This development could not only significantly shorten waiting times but also significantly decrease the risk of rejection.

Other Improvements

Cell therapy, including new methods using stem cells, aims to help the body accept transplants without needing lifelong medication to stop rejection (i.e., tolerance). For patients, this could mean living without the risk of medication side effects like infections and cancer. Cell therapy might also be used in ways that could make the need for a transplant unnecessary.

Artificial Intelligence (AI) is improving the organ matching process (i.e., helping people in need match better with new organs), predicting how well the transplant will go, and choosing the best medicines to prevent rejection and side effects. For people who get transplants, this means a better chance of success and care.

Even though these new technologies are exciting, as with any new technology, there are limits, rules, ethical issues, and high costs. But the potential benefits, such as living longer, having fewer health problems, and more available organs, are very important for people who need transplants.

The shift towards these new technologies could redefine the definition of “normal” of post-transplant care, offering recipients a life that is not only longer but also free from the burdens of current immunosuppressive medicines.  Understanding these new developments is essential for transplant patients to make more informed decisions about their health.

In conclusion, the current advancements in the development of transplant medication are set to potentially revolutionize the field, directly impacting recipients by offering them safer and more effective treatment options, a potentially limitless organ supply, and a significantly improved quality of life. These changes highlight why recipients should remain informed, supportive, and proactive about the evolving landscape of transplant medicine.

This article is made possible by the support of ITB-MED LLC. 

Glossary

Artificial Intelligence (AI): Computer systems that can help doctors match organs to recipients, predict transplant outcomes, and customize drug treatments to reduce rejection and side effects.

Belatacept: A drug that helps prevent organ rejection by blocking the activation of T-cells, which are part of the immune system.

Calcineurin Inhibitors (CNIs): A type of medication used to prevent organ rejection, but they can harm the kidneys and cause other side effects like high blood pressure, memory problems, and diabetes.

Cell Therapy: Using cells, like stem cells, to treat diseases and help the body accept a transplanted organ without needing strong immune-suppressing drugs.

Ethical Issues: Concerns about what is right or wrong in medical practices, such as using animal organs in humans.

Gene Editing: Changing the genes of an animal to make their organs more suitable for human transplantation.

Immunosuppressive Regimens: The specific plan and types of drugs used to keep the immune system from rejecting a transplanted organ.

Nephrotoxic: Something that is harmful to the kidneys.

Organ Matching: The process of finding the best donor organ for a recipient based on various factors to increase the chances of a successful transplant.

Post-Transplant Care: The ongoing medical care and treatment that a patient needs after receiving a new organ.

Quality of Life: The general well-being of a person, including their health, comfort, and happiness.

Regenerative Medicine: Using techniques to regrow or repair damaged tissues and organs in the body.

Stem Cells: Special cells that can develop into different types of cells in the body and can be used to repair or replace damaged tissues.

Tissue Engineering: Creating new organs from a patient’s own cells to reduce the risk of rejection and eliminate the need for a donor organ.

Transplant Medications: Drugs that help the body accept a new organ and prevent it from being rejected.

Xenotransplantation: Transplanting organs from animals, like pigs, into humans.

 [LB3]“may” or will?

For transplant patients, the journey doesn’t end with a successful surgery. One of the critical aspects of post-transplant care is the use of types of drugs called “immunosuppressants”. These medications play a critical role in stopping the body’s immune system from rejecting the new organ. Understanding the types, functions, and importance of these medications, as well as the challenges in managing them, is very important for transplant recipients.

Types of Transplant Medications and Their Functions

Immunosuppressants can be broadly classified into several categories, each playing a unique role in ensuring the transplanted organ is not rejected:

  1. Calcineurin Inhibitors (CNIs): These include drugs like cyclosporine and tacrolimus. CNIs inhibit (i.e., slow down or stop) the activity of calcineurin, a protein that activates T-cells of the immune system thereby preventing rejection.
  2. Antiproliferative Agents: Medications such as mycophenolate mofetil (MMF) and azathioprine fall into this category. They work by inhibiting the growth of immune cells, further reducing the risk of rejection.
  3. mTOR Inhibitors: Drugs like sirolimus and everolimus inhibit the mammalian target of rapamycin (mTOR), a key protein involved in cell growth and proliferation, thus helping control the immune response.
  4. Steroids: Prednisone is a common steroid used to reduce inflammation and suppress (lower the activity of) the immune system. While highly effective, long-term use can lead to significant side effects.

NOTE: these are complicated terms and it may be hard to understand. Keep reading and refer back to the four types of drugs as needed.

Importance of Adherence to Medication Regimens

Adherence, which means consistently taking your medicine as instructed by your doctor, is crucial for transplant patients. Missing a dose of medication or not taking your medication at the correct time can lead to not having enough of the drugs that calm the immune system, which would increase the risk of organ rejection. Conversely, taking too much can be harmful as well. Therefore, it is very important for patients to follow their medication schedule with great care, go to their doctor and laboratory appointments, and share any issues with their healthcare team.

Challenges in Transplant Medication Management

Managing transplant medications can be hard due to many factors, including side effects, complications, and the complexity of the medication regimen.

Side Effects and Complications

Immunosuppressants, while lifesaving, come with a range of side effects. Common issues include:

  • Infections: Suppressing the immune system increases the risk of infections.
  • Kidney Damage: Particularly with CNIs, these drugs can hurt your kidney over time due to scarring.
  • High Blood Pressure and Diabetes: These are common side effects of steroids and CNIs.
  • Gastrointestinal Issues: Such as nausea, vomiting, and diarrhea, often seen with antiproliferative agents.
  • Neurotoxicity: Tremors (or shaking), the most common finding, but also difficulty sleeping, brain fog, headache, dizziness, impaired sense of touch, light sensitivity and mood disturbance
  • Cancer: Skin cancers, lymphomas, and other malignancies, as the immune system’s ability to detect and destroy cancerous cells is diminished.

Strategies for Managing Side Effects

Effective strategies to manage side effects include:

  • Regular Monitoring: Transplant recipients need to get frequent blood tests to measure the levels of drugs in their system (and make sure there is not too much or too little of any drug) and to test how well the kidney is functioning.
  • Lifestyle Adjustments: Transplant recipients can change their diet and add or modify their exercise routine to help manage or avoid high blood pressure and diabetes.
  • Preventative Medications: Sometimes doctors will prescribe antibiotics (that fight infections) or antivirals (that fight viruses) to prevent infections (especially during the first few months after the transplant).

Addressing Non-Adherence and Its Implications

Non-adherence (not taking drugs as prescribed by your doctor) to immunosuppressant therapy can lead to severe consequences, including acute organ rejection and failure of the new transplant. Why would someone not take their medicines? Well, it is a pretty complex combination of drugs that need to be taken consistently, there is the possibility of side effects that might not be pleasant, and perhaps some people do not understand how important these medications are.

Some tips to keep on the program as prescribed by your doctor:

  • Educate: Learn as much as you can about your drugs and how important they are. Also learn from other transplant recipients how they are managing to follow their routines successfully. Check out more articles on TransplantLyfe to help stay informed and meet people who are on the same journey.
  • Simplify: Ask your doctor if there are any combination pills or options to reducing the number of daily doses to make it easier for patients to stick to your schedule. Perhaps try a pill box to sort drugs into morning and evening groups. And you can plan your drugs for the week ahead. You can also use an alarm clock or your phone to set reminders.
  • Support: Ask family members, care partners, or support groups to help out. Reminders to do what you are meant to do, as well as a good bit of emotional support, are helpful.

Conclusion

Immunosuppressant medicines are a very critical part of post-transplant care as they are essential for preventing organ rejection. Understanding the different types of medications, their functions, and the importance of taking them correctly are crucial for transplant patients. While challenges exist, there are ways to help manage these issues, ensuring the long-term success of the transplant. Always consult with healthcare providers to ask questions and learn how to match the professionals’ recommendations with your individual needs and circumstances.

This article is made possible by the support of ITB-MED LLC. 

What is Immunology?

Immunology is all about how our bodies defend themselves against germs and other invaders. Imagine your body as a castle, and the immune system is the army protecting it from enemy attacks. This army has cells, tissues, and organs. They work together to keep you safe from viruses and bacteria.

But here’s where it gets really interesting: the immune system isn’t just about fighting off bad guys. It also helps our bodies accept or reject things that don’t belong, like when someone gets an organ transplant. See, when someone gets a new organ, their immune system might see it as foreign, think it is a threat and try to attack it, thinking it’s an invader. Immunology helps us understand how to prevent this from happening, so the new organ can stay and do its job without any trouble.

In simple terms, immunology is about how our bodies stay healthy. They do this by fighting off germs and ensuring that everything inside works well together.

What is Rejection?

Rejection is when the body’s defense system, called the immune system, treats a transplanted organ or tissue as if it doesn’t belong.  This can cause serious damage or even make the new organ stop working. To prevent this, doctors use special medicines called immunosuppressive medicines to calm down the immune system and stop it from attacking the new organ.

Types of Rejection

There are three types of rejection that transplant patients may experience:

  1. Hyperacute Rejection: This is when rejection happens super quickly, within minutes to hours after the transplant. It’s not very common nowadays because doctors are really good at matching organs to patients. But if there’s a big mismatch in blood type or other cells in the body (called major histocompatibility complexes) it could still happen.
  2. Acute Rejection: This is the most common type and it usually occurs within days to months after the transplant. Even if doctors give patients medicines to calm down (or “modulate”) their immune systems, some level of acute rejection can still happen.
  3. Chronic Rejection: This is the trickiest type because it can take months or even years to show up. With chronic rejection, the organ slowly stops working as well as it should. It’s a more complicated situation because it can involve lots of different factors, not just the immune system.

Causes of Rejection

Rejection mostly happens because of genetic differences between the person who gets the organ (the recipient) and the person who donated it. This means the body might notice that something in the new organ is a bit different from its own.

HLAs (human leukocyte antigens) are like little tags or markers on our cells. They help our immune system recognize which cells belong to us and which ones do not. Imagine each cell in your body wearing a name tag. Your immune system looks at these name tags to make sure everything is okay. But when someone gets an organ transplant, the new organ might have different name tags (HLAs) than the rest of their body. This can confuse the immune system and make it think the new organ is an intruder.

If your immune system spots an intruder, it can fight against this new organ, leading to rejection. Even though doctors give patients medicines to calm down their immune systems, they can’t completely get rid of the risk of rejection.

Signs of Rejection and Monitoring

It’s really important for someone who has had a transplant to keep an eye out for signs that their body might be rejecting the new organ. Here are some things they should watch for:

  • Pain or swelling where they had the transplant
  • Fever
  • Feeling tired a lot
  • The organ not working as well as it should (like making less urine if it’s a kidney transplant)
  • High blood pressure (for kidney transplants)
  • Having trouble breathing (for lung transplants)

It’s also important for organ recipients to see their doctors regularly so they can do tests to make sure everything is going okay. These tests might include blood tests, imaging (pictures of the inside of the body), and sometimes biopsies, which is taking tiny pieces of tissue from the organ to check it under a microscope. This helps catch any rejection early so it can be treated quickly.

What is Tolerance?

Tolerance in transplant means that the body accepts the new organ or tissue without needing lots of medicine (immunosuppression) to keep the immune system calm. It’s like the body and the new organ becoming best friends, so the immune system doesn’t see it as a stranger anymore.

Scientists are working hard to figure out how to make this happen more often because it would make life a lot better for people who get transplants. They’re trying different methods, like using special immune cell types, certain therapies that change how the immune system works, and even new techniques like gene editing. The goal is to teach the immune system to treat the new organ like it belongs in the body, instead of trying to get rid of it.

Conclusion

Understanding how the body’s defense system works, which is called immunology, is really important for people who have had transplants. To make sure the new organ stays healthy and works well, it’s crucial for transplant patients to:

  1. Know the signs that the body might use to tell them that it might be rejecting the new organ;
  2. Take their immunosuppressive medicines as instructed by their doctors; and
  3. Go to their doctor for check-ups and testing regularly.

Scientists are hopeful that as they continue doing research, they will find ways to enable the body to more easily accept new organs, making a huge difference in the lives of people who have had transplants.

This article is made possible by the support of ITB-MED LLC. 

Glossary

Acute Rejection: A type of rejection that occurs within days to months after a transplant. It is common but usually treatable if caught early.

Biopsy: A medical test involving the removal of a small piece of tissue to examine it for signs of disease or rejection.

Chronic Rejection: A type of rejection that happens over a long time, causing gradual damage to the transplanted organ.

Gene Editing (CRISPR): A technique used in research to alter genes to help the immune system accept transplanted organs.

Human Leukocyte Antigens (HLAs): Proteins on the surface of cells that are unique to each person and help the immune system recognize which cells belong in the body and which do not.

Hyperacute Rejection: A type of rejection that happens very quickly, within minutes to hours after a transplant, due to immediate blood clotting in the transplanted organ.

Immune System: A complex network of cells, chemicals, tissues, and organs that work together to defend the body against harmful invaders.

Immunology: The study of the immune system, which protects the body from harmful things like viruses, bacteria, and even transplanted organs.

Immunosuppressive Drugs: Medications that reduce the activity of the immune system to prevent it from attacking the transplanted organ.

Long-Term Immunosuppression: Ongoing treatment with immunosuppressive drugs to prevent rejection of a transplanted organ.

Monitoring: Regular check-ups and tests with healthcare providers to detect and treat any signs of rejection early.

Rejection: When the immune system attacks a transplanted organ or tissue, thinking it is harmful.

Tolerance: A state in which the immune system accepts the transplanted organ as part of the body and does not attack it, reducing the need for long-term immunosuppressive drugs.

What are Endpoints? How can endpoints make clinical trials more patient-friendly and lead to better drugs?

Introduction

Clinical trials are essential for discovering new treatments and medical procedures. A critical part of these trials is choosing and evaluating endpoints, which are the key results used to measure a trial’s success. This article explains the goals and different types of endpoints in clinical trials, the importance of patient-reported outcomes, and how to design better trials, especially for transplant patients.

Understanding Objectives and Endpoints

The main goal of a clinical trial is to see how well and safely a treatment works. Endpoints are the specific results or events used to measure the trial’s success. For example, in cancer trials, an endpoint might be a reduction in tumor size. In transplantation trials, it could be how well the new organ is working. Other general health indicators include survival rates and the severity of side effects.

Different Types of Endpoints

There are several types of endpoints in clinical trials:

  • Primary Endpoints: The main results used to determine if the treatment is successful.
  • Secondary Endpoints: Additional results that provide more information about the treatment’s effects or side effects.
  • Exploratory Endpoints: Used to explore other potential outcomes and generate ideas for future research.
  • Surrogate Endpoints: Substitute markers that are believed to indirectly reflect longer-term patient outcomes.

Surrogate endpoints are used when the primary endpoints take too long to measure. For example, lowering blood cholesterol might be used as a surrogate endpoint for preventing heart attacks.

Outcomes

Clinical outcomes (results) come from many sources. There are data collected from objective measures like an X-ray or a blood test.  Patient-reported outcomes (PROs) are one type of clinical outcome assessment becoming more important in clinical trials.

Others include clinician-reported outcomes (ClinROs), which are health assessments made by doctors, observer-reported outcomes (ObsROs), which are evaluations by care partners, and performance outcomes (PerfOs), which are measures of a patient’s ability to do certain tasks.

PROs are results based on what patients say about their own health, symptoms, and quality of life. Including PROs in trials helps make research more focused on the patient, enabling healthcare providers to understand the experimental drug’s benefits and side effects from their perspective.

Using PROs can greatly improve drug development by:

  • Providing direct insights into the patient’s experience, leading to more patient-centered drug development.
  • Identifying benefits or side effects that might not be seen through traditional measurements.
  • Providing additional data that can aid in the approval process by showing clear benefits from the patient’s viewpoint.

Future Clinical Trials Design for Improved Outcomes After Transplantation

Designing better clinical trials for transplantation should focus on improving long-term patient and organ survival. This involves:

  • Enhancing Endpoint Selection: Using a mix of traditional and new endpoints, including molecular and genetic markers, which allow for more precise tailoring of the response, to predict organ function and survival, as well as patient response and changes.
  • Incorporating Comprehensive PROs: Including endpoints that reflect the patient’s quality of life after transplantation, which is very important in evaluating the success of the procedure.
  • Utilizing Adaptive Trial Designs: These allow changes based on early results, potentially reducing costs and time, and improving the relevance and ethical aspects of the trials.

Conclusion

Rethinking endpoints in clinical trials is vital for advancing medical research and improving patient care. By including patient-reported outcomes and refining endpoint selection, especially in transplantation, researchers can achieve more meaningful and impactful results. Moving forward, clinical trial designs should better match the complexities of human health, ensuring new treatments and procedures are both effective and patient centered.

This article is made possible by the support of ITB-MED LLC. 

Glossary

Endpoints: The key results used to measure a trial’s success

Genetic Markers: Pieces of DNA that can provide information about a person’s risk for certain diseases or how they might respond to a treatment.

Molecular Markers: Tiny parts of cells, like proteins or DNA, that can give clues about how an organ is working or how a disease is progressing.

In Partnership with CSL Behring

If you are new to clinical trial research participation but are interested in learning more, the first step is to let your transplant team know that you would like more information about clinical trials. Your doctor is your primary source of information about which trials are available at your transplant center and for which you may be eligible. It’s important for you to ask your healthcare team questions to better understand whether clinical trial participation might be a good option for you.

Types of Available Trials

There is an ever-growing number of clinical trials available for kidney transplant recipients, including:

  • the evaluation of new anti-rejection and anti-infection medication.
  • trials assessing the use of different incisions and approaches to surgery, especially minimally invasive procedures performed with laparoscopy or robotics.
  • trials to evaluate various combinations of more tolerable treatments.
  • to minimize the use of anti-rejection drugs.

While doctors may not be up-to-date on all possible treatment options, your doctor may be able to direct you to national resources on the internet or to other healthcare centers.

Understanding Your Individual Treatment History and Goals

Before asking about available clinical trials, it’s important to understand your diagnosis and specific treatment history. Being informed about your full experience will help your doctor better determine your participation eligibility. Clinical trials have specific eligibility and exclusion criteria:

  • eligibility criteria means that to participate, you must meet specific requirements.
  • exclusion criteria means you must not have other specific reasons that would prevent you from participating in a trial.

Different trials may have varying levels of potential risk and benefit based on many factors including the type of study, the potential drug or potential therapy that is being tested, and the disease or condition being studied.

This is why it’s important to ask your doctor how trials will differ in meeting your individual needs and goals. It is also important to think about

  • how much time you are willing commit
  • how far you are willing to travel
  • the potential side effects of the trial treatment
  • what your goals are for your overall health if you decide to participate

Keeping track of these expectations should help you make an informed decision about participating in a trial.

Starting the Process

If you find a study in which you are interested in participating, you or a member of your transplant team can contact the person listed as the study coordinator or recruitment specialist. During the discussion about your eligibility, be sure to ask questions to confirm your eligibility, find out what the next steps are, and what will be required of you during the trial.

Details such as:

  • the frequency of visits.
  • personal cost and insurance coverage.
  • duration of the trial.
  • any required testing (what type and how often).

are important to walk through with the study team.

There are many factors that you must consider to determine if a trial is appropriate for you. The details may sometimes be overwhelming. You should never feel compelled to make a decision, and you should only make a decision until you have learned as much as you can about your disease, your overall health condition, and about various available treatment options. In most instances, you are not permitted to be enrolled in more than one study at a time.

If you find a trial that seems like the right fit for you, let your transplant team know you are interested so that you can talk to them about your options and potential eligibility.

If you are ready to begin searching for trials on your own outside of your transplant center, these are a few resources to explore. Visit ClinicalTrials.gov, which provides recipients and care partners with a national, relatively simple access to information about ongoing clinical trials. Additionally,  WCG Center Watch, American Society of Transplant Surgeons, and American Society for Transplantation have lists of clinical trials that are currently enrolling kidney transplant recipients.

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Possible Benefits of Being Part of a Clinical Trial

As a research participant, you help researchers explore potential new treatments. Through participating in a clinical trial, you may also learn more about your condition, which can help in your disease management. The insights that come from research studies help those in the medical field learn new ways to help others with your condition.

Possible Risks of Being Part of a Clinical Trial

Research participation does not come without risks. The study treatment or study medication being tested may not make you feel better, or could make you feel worse, for many reasons, including:

  • interacting with your other medications
  • starting at an unideal time in the course of your disease progression
  • not working in humans like it did in earlier experiments
  • working better in one sex or certain racial/ethnic background
  • risks inherent to the study drug or how it is administered

New treatments are not always better than standard treatments and could, for instance, potentially be less safe or less effective, or could potentially interfere with the treatments you are currently receiving. You will likely have more medical visits, and you may spend additional funds on matters such as travel. The cost of medications and tests that are not part of your standard of care may be covered by the study, but it’s important to review this with the study staff to ensure you’re fully informed before you decide to participate. There is also the risk that the treatment may have known or unknown side effects, which can result in various types of complications. The study will be stopped by an independent group of scientists (called an Institutional Review Board) if the rights and welfare of the study subjects are not properly protected.

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Clinical trials for transplant recipients evaluate different types of potential treatments in individuals who are waiting for or have already received a transplant. These studies may examine new anti-rejection and anti-infection drugs, new approaches to surgery, or new combinations of treatments.

The goal of clinical trials is to gain knowledge and understanding whether potential study treatments can safely and effectively meet certain study criteria, such as prolonging life expectancy, prolonging survival of the transplanted organ(s), improving a person’s quality of life, and improving current medications.

What is the Process to be Accepted for a Kidney Transplant Clinical Trial?

Prior to being accepted to a clinical trial, you will be screened to make sure that you qualify for the trial based on inclusion and exclusion criteria.

  • Eligibility criteria means that to participate, you must meet specific requirements.
  • Exclusion criteria means you must not have other specific reasons that would prevent you from participating in a trial.

If accepted into the trial, the first visit consists of required testing, such as cognitive and/or physical tests. If the study is a randomized controlled trial (RCT), you will be randomly assigned to a treatment or control group. The randomization process determines:

  • who receives the medication or procedure (treatment group)
  • who receives a placebo or standard procedure (control group).

Randomization is usually done by a computer program. Randomization may be blind, which means that the doctor (PI) and/or the study coordinator may or may not know what study therapy the participants receive.

Deciding Whether or Not to Participate in a Clinical Trial

Before you agree to participate in a clinical trial, an investigator and/or a study coordinator will explain to you in detail:

  • the goals and purpose of the designated clinical trial
  • the plan and methods for any required visits and tests
  • the possible side effects of the tested agent that you may experience
  • how participation in the study might affect your daily life
  • how your transplant might be affected by or without the treatment
  • and what is expected to happen to you and your transplant during the clinical trial itself and predictably afterwards.

During this initial discussion about the trial, you will have the opportunity to ask any questions that you might have about the clinical trial, including the potential results and any concerns about complications. The research team will give you an “informed consent form” that explains the details of the clinical trial, including known risks and side effects and their potential severity. You will be informed about the voluntary entry and exit from the study, the process of being in the study, and reasons why you may need to be removed from the study. You may also review and share this form with your doctor, care partner, or family, when deciding if enrolling in a clinical study is right for you.

If you decide to take part in the clinical trial, you will sign the informed consent form in the presence of someone from the study team. This will likely be either the principal investigator (PI) of the study or your primary transplant physician, depending on how the study is set up. After you sign the informed consent form, you can change your mind and withdraw from the clinical trial at any time, and for any reason or no reason at all, either before or during the trial.  Deciding not to be in a clinical study, or leaving a clinical study at any time will not jeopardize your medical treatment you would otherwise receive.

What to Expect During a Clinical Trial

Throughout the trial, trial participants must report any issues or concerns to the research team. There will be regularly scheduled visits for evaluations, testing and discussions. Some follow-up visits may also be conducted by video or telephone. During these visits, the research team collects information about the effects of the treatment and reviews each participant’s health and safety. When the trial concludes, you will no longer have scheduled visits and testing specifically for the study, but you may continue to be seen regularly by the doctor or PI of the trial. Furthermore, you will no longer receive the treatment being studied after the trial, unless explicitly allowed.

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By Alisha Hiebert

Having a loved one go through any kind of chronic illness and/or life-changing health diagnosis can be incredibly challenging. There is no simple guidebook for when the unexpected happens, and handling change can be tough when treatment options become more experimental and possible outcomes become less predictable.

Preparing for Change

Going through a clinical trial can be a disorienting experience, not only for the recipient but for their entire support team. It can be difficult to be fully prepared for the changes that might affect the recipient’s treatments and daily ritual.

It is important to remember that clinical trials have safeguards in place to ensure that the participant’s rights are protected. What a participating recipient might need most from their caregiver isn’t necessarily medical treatment or advice– but rather emotional support. This includes:

  • Acknowledging their fears and concerns.
  • Validating their feelings.
  • Listening with the intent of supporting rather than responding.
  • Making sure the recipient knows they have someone to lean on emotionally when they are struggling with their physical health.

A Caregiver’s Self Care

As a caregiver, it can easily become overwhelming to listen to a loved one’s experiences without being able to provide direct solutions. The emotional toll that might result from participating in a clinical trial can affect the caregiver just as much as it affects the recipient. As a caregiver it is also important to avoid sacrificing personal health when caring for a loved one.

  • Try setting boundaries that allow the caregiver to have personal time for self-care.
  • Enlist external resources to allow the caregiver to decompress regularly, such as utilizing other friends and family. 
  • Allow time for a caregiver to process emotions and prepare for change at their own pace.   

Recipients and caregivers need support, especially in situations filled with so many unknowns, such as in the case of clinical trials. Making sure that you are taking care of yourself is crucial to being supportive care partner.

Delegating Care to the Community 

While all focus and attention seem to be consumed by medical events, it can be easy for the recipient to lose sight of the day-to-day things that still need to get done. This is something that can be delegated to members outside of their support tier. A recipient may not be comfortable asking their community for help when they need it, so offering suggestions can aid in their ability to reach out for extra care. Additional support can include:

  • Sending a quick text at the grocery store to see if the recipient needs anything.
  • Having a neighbor mow the recipient’s lawn after completing their own.
  • Dropping off gift cards for gas for food or freezer meals for when the recipient needs a quick and easy dinner.  
  • Inviting the recipient’s kids over for a playdate to get them out of the house.

These are only a couple examples of easy things that can provide immense support for someone going through a health challenge. Never underestimate the value of simply checking in- a small gesture of support can go a long way.

Using Resources and Doing Research

Depending on the trial setting, some hospitals have caregiver support groups, which can also be a valuable resource. If you’re unsure of what support is available to you, it can be helpful to:

  • Ask the nurse, coordinator or social worker on your medical team. 
  • Reach out to other transplant recipients in your area.
  • Participate in transplant recipient forums, Facebook groups, etc.

In clinical trial settings where so much is still undetermined, it can be frustrating to try and understand everything or get adequate answers. Your loved one may not have the time or emotional capacity to educate you, nor is it their job to do so. This is a great opportunity to do your own research. You can:

  • Speak to the medical team involved
  • Read any information provided by the medical team.
  • Read online forums and materials related to the specific transplant type. 
  • Ask questions.

Knowing as much as possible about what is expected, the goals of the trial, and potential side effects can be helpful in assisting and advocating for your loved one. It can be easy to get overwhelmed as a care partner but remember this: it takes a village to get through major changes in healthcare and what your loved one needs most is a strong support system. Just being a supportive presence can help make even the toughest time a little bit easier. Obtaining information on the clinical trial and how to be the best caregiver for a recipient is a step in the right direction.

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Self-advocacy is a key component to navigating life in the world of medicine. The healthcare system, while a vital resource, is just that: a system. It is designed to be effective and efficient, providing assistance to those who need it. However, in doing this, it can sometimes lose sight of recipient-oriented care.

While doctors know science and research, only the recipient knows what it is like to live in his or her body, and, ultimately, the recipient is the one who has the most invested interest in the care being given. If your body was a company, you could consider yourself the CEO.

How to Become Your Best Advocate

The foundation of self-advocacy is understanding your condition. Doing your own research is an important part of this. Doctors are a valuable resource since they have conducted a lot of research about a specific topic, but there is room for the recipient to step into the position of being the expert on their own case. Even in the same disease area, there can be a variety in presentation and symptomatology. Your own lived experience, and learning from the lived experiences of others, can be a very useful tool. This can be something as simple as reading medical journals to find articles that relate to your specific diagnosis or set of symptoms. Knowledge is power and the more you know, the more prepared you will feel when it comes time for the doctor’s appointment or hospital visit.

In addition to doing your own research and discussing with your physician, it’s also important to ask valuable questions. Knowing the risks and benefits of each viable treatment, anticipated outcomes, alternative diagnoses for symptom presentation etc. is very important to making informed decisions. Ask questions, and keep asking until you feel as though you’ve gotten an answer.

You can request all concerns, tests refused and treatments tried to be documented in your chart if your team consists of more than one provider or if you are interested in seeking a second opinion. Having your own copy of all relevant medical records is also a good idea. This saves you the time and energy of having to explain it and leaves a tangible trail to reference in determining future diagnoses, tests and treatment.

Finding Support in Self-Advocacy

If you are struggling to voice your feelings and concerns, it can be helpful to bring someone with you to help you advocate or to help absorb information. FaceTime or speakerphone calls can be a way to involve a care partner if one cannot physically attend the appointment with you. It can also be helpful to write down key questions or concerns you wish to have addressed beforehand and bring them with you.

It helps to know that it is within your right as a recipient to get a second opinion or to request a different provider if you feel your concerns are not being addressed. In certain situations, and with certain types of health insurance, a self-referral is able to be made by directly contacting physician’s office as opposed to coordinating communication between multiple care providers. This can be a valuable resource to recipients who feel their needs are not being met.

The key to surviving and thriving as a recipient within the medical system is to be your best advocate. Knowing you are in charge of your own body and care plan can prevent many unwanted headaches. Keeping detailed documentation, doing your own research and voicing your opinion can be the difference between feeling like a victim and feeling empowered.