Medical Trials and Research
Many patients have participated in research & clinical trials over the years in various areas of lung and PH research. Generally if you are already a diagnosed patient with PH and on medications for your PH this may exclude you from trials as they are seeking people who have not yet had treatment to see how they respond.
As you are already on medications and cannot be taken off them they may then use your information for other areas of research and data collection or statistics (with consent). There are other trials held particularly by the Institute for Respiratory Health that you may be interested in, find their information below and on their website.
If you want to know more about the clinical trials and research being conducted through your clinic or in WA please ask your PH Nurse Coordinator and Doctor's for more information & to see if there is anything suitable for you to participate in.
Understanding the Clinical Trial Process
Frequently Asked Questions
There are many benefits to being involved in a clinical trial, but the most important is the contribution you will be making to science and research. Without volunteers, many drugs could never be approved for general use. We are grateful to everyone who volunteers. Below will answer any questions you may have regarding a clinical trial.
What is a clinical trial?
Clinical trials are the gold standard tests for decisions on whether a treatment works and if it is more effective than an alternative treatment. Clinical trials are research studies involving people. They test ways to treat and prevent disease. The design of a clinical trial ensures that the results have not been influenced by any factors such as the interpretation of test results, or selection of patients into a particular treatment group. All of today’s standard treatments for lung disease are a result of clinical trials completed many years ago.
Who organises a clinical trial?
Organizations, particularly drug companies, looking for better treatments for lung disease are the usual bodies that develop and fund clinical trials. Our Clinical Trials Unit is then contracted to conduct the trial. Every trial has a person in charge, usually a doctor, called the Principal Investigator.
All clinical trials conducted by our team have been registered with the Australian Therapeutics Goods Authority and have received ethics approval from an approved Human Research Ethics Committee. In addition, we scrutinize the study design and do not participate in any trials unless we are completely happy with it. Patient participation in clinical trials is completely voluntary, the patients are free to withdraw if they choose to.
What's Involved in the actual trial?
Every trial is different. If you are accepted on to the trial, most involve either regularly taking either an active drug or a placebo. Most trials are ‘double blind’, meaning neither you, nor the nurses know whether you are receiving the active drug or not. After a time, lots of trials that have had positive results become ‘open label’ which means everyone who was previously taking a placebo will receive the active drug.
The benefits to your health are very positive whether you are on the active drug or not. Regular health checks by health professionals mean you have more personalised and regular care, and most of the our patients report an increase in the management of their conditions and better wellbeing as a result of their increased healthcare. Volunteering for a clinical drug trial is a commitment, but the positive health benefits certainly outweigh any inconvenience – and all expenses are paid.
Who can participate in a clinical trial?
Each clinical trial has certain criteria that a volunteer must meet to be included in that trial. This can include:
Register for an upcoming clinical trial with the "Institute"
What are the benefits for me?
Although there are risks with any treatment, there are also many benefits from taking part in a clinical trial, including:
What are the risks for me?
All clinical trials have risks, because any medical test, drug or procedure has risks. The risk may be greater in a clinical trial because some aspects of any new treatment are unknown. This is especially true of phase I and II clinical trials, where the treatment has been studied in fewer people.
In our trials, we assess all patients for suitability for the trial, and if we feel that participation in the trial may endanger your health, then you would be advised not to enrol. Close monitoring is the hallmark of all clinical trials, and allows any adverse effects of the treatment or unexpected deterioration in health to be detected early and steps taken to cease treatment or give additional care.
New drugs or treatments may not be any better than the standard care they are being compared to. If you are in a randomized trial, you will not be able to choose if you are getting the new treatment, the standard approach or a placebo.
Will I be a guinea pig?
The ultimate purpose of a clinical trial is to answer a medical question, but every effort has been made to understand and reduce the risks during pre-clinical and earlier clinical studies
Will I get a placebo?
Each clinical trial is designed differently:
Unfortunately neither you nor the doctor can choose which treatment you get on a trial.
Will my information be kept confidential?
As much as possible, all of your personal and medical information will be kept confidential. Of course, your health care team needs this information to give you the best possible care, just as they would if you were not in a clinical trial.
Medical information that is important for the study, such as test results, is usually put on special forms and into computer databases. This is then given to the people who will analyze the study results. Your information is assigned a number or code — your name is not on the forms or in the study database.
Sometimes, members from the research team or from the Food and Drug Administration may need to look at your medical records to be sure the information they were given is correct. But your personal information is not given to them and is never used in any published study results.
What will I need to do?
Although pulmonary arterial hypertension was discovered in 1891, there were no known treatments for the disease until 1994 when Flolan was introduced. Previous to the release of that medication, the prognosis and life expectancy for a patient with pulmonary hypertension was around 3 years and it took an average of 2 years to accurately diagnose a patient. Flolan was the first drug to increase the life expectancy by up to 5 years for pulmonary hypertension patients. While we do not currently have a cure for the disease, several more treatments have been approved for PAH thanks to research. The most recent studies have shown improved average survival now at 7 years. However, survival at centres of excellence is probably even better. Over the past 20 years, we have gone from no medications to treat PAH to over 10 medications. Even more medications are being studied. We are optimistic that our patients will continue to experience longer survival and better quality of life.
Key players in research for pulmonary hypertensionThe advancements in treating pulmonary hypertension patients would not have been possible without research. There are several key players in bringing a drug to market or making it available for patients. The drug companies who set up the research study for the specific drug, the pulmonary hypertension centres that become participating sites for the studies, and most importantly the pulmonary hypertension patients who enrol in the research studies. Research is such an important piece of bringing new therapies to market that the PHA (Pulmonary Hypertension Association) requires all of their Comprehensive Care Centers to have a fully functioning research department.
Who can participate in pulmonary hypertension research
Each research study has strict rules about what types of patients can be enrolled, how the drug will be administered, and what measurements will be used to determine the results of the study. Many of the studies have requirements of what background therapy a patient can be on before they are enrolled in the study. For example, protocol (rules of the study) might say a patient cannot be on any treatments for pulmonary hypertension prior to enrolling in the study or protocol might say they can be on Adcirca or Revatio but not Letairis or Tracleer. It is becoming more and more difficult to find pulmonary arterial hypertension patients to enroll in studies as many of them are starting therapies with physicians outside of specialty clinics and disqualifying themselves as research candidates.
Research, Life Expectancy & Prognosis for PH
Researching treatments and a possible cure
for pulmonary hypertension
Steps to participating in research for pulmonary hypertension
Most pulmonary hypertension centers of excellence participate in research studies. If the physician you are currently working with does not participate, inform them that you would like to learn more about research studies for treatments for pulmonary hypertension.
They may be able to refer you to a center currently enrolling patients in studies. Research is completely separate from clinical management of the patient meaning your current physician will continue to participate in your care. It is important for potential research patients to understand the risks and benefits of enrolling in a research study and what will be expected of them throughout the study. The patient will be asked to take home information about the study and read through it and come back to discuss any questions or concerns.
Once all of their questions are answered they will be asked to sign an informed consent if they are interested in participating. It is important to understand that while a physician may offer the patient the chance to participate in a study, the decision is always up to the patient. Some patients will want to participate in research but not fit the specific rules of the current research studies enrolling. The sponsor (usually a drug company) of the study is ultimately responsible for deciding which patients are eligible to enrol.
Once you are enrolled in a research study, you may choose to stop at any time. This is called withdrawing consent. You will not be punished or suffer any negative consequences from your doctor if you choose to stop participating. Some studies last a few months and others last many years. We are very excited about research. Through your participation we are able to improve the care of all patients with PAH.
Drug Failure in Clinical Trials: Lessons to be Learned
June 29, 2016 - by Phyllis Hanlon, Contributing Writer
Developing a safe, effective drug for any medical condition requires years, sometimes decades, of research, a series of clinical trials and an enormous amount of funding. And not all clinical trials are successful. Sometimes all that effort fails to result in a drug that works safely and effectively to treat a condition in humans. Pharmacology & Therapeutics recently published an article that explores the reasons some drugs targeting pulmonary arterial hypertension (PAH) fail in clinical trials.
Mark P. Lythgoe, clinical fellow at Imperial College, London, and colleagues examined case studies that provide insight into how and why a drug is selected for a clinical trial; when and how researchers should evaluate the study subjects’ responses to both the drug and its dose; and the importance of selecting subjects with the same genetic makeup. The combination of these factors can have an impact on the success or failure of a clinical trial.
The authors of this article point out that there are lessons to be learned from failed trials. First, to develop an appropriate drug to treat PAH, researchers must understand the underlying characteristics of the disease, including, for example, the way it affects tissues in the body, clotting time and inflammation. Some of the drugs currently on the market for PAH reduce vascular tone but have minimal impact on cardiopulmonary functioning. In other words, these drugs reduce how constricted some of the blood vessels in the lungs are, but only reduce the mean pulmonary artery pressure, on average, around 5 mmHg While these drugs improve the patient's well-being, they have not been shown to significantly reduce mortality in trials. So researchers are looking to develop drugs that directly impact different parts of the vessel wall.
Another aspect to consider is the dose of drugs and method of administration during clinical trials. When it comes to dosage, one size does not fit all. It is critical to monitor dosing responses in early clinical trials (“Phase I” and “Phase II”) so decisions whether to continue with the drug can be made early. If a trial continues for six months with no structural changes in the patient, the target (i.e., the type of patient) or dose may be wrong. Waiting this long for a response “is unacceptable,” according to the authors.
Studies should be designed to capture data in order to compare subjects to respond to treatment to those who do not. For example, a trial of imatinib, which was originally developed as Gleevec® to treat chronic myeloid leukemia (CML), was conducted in patients with PAH in the IMPRES study as an “add-on” therapy. Although Phase II did not meet six-minute walk distance (6MWD) significance, for the most part, the Phase III study was successful, meeting its goal of improving the 6MWD. Additionally, cardiac functioning improved and pulmonary vascular resistance decreased. But, for some reason, compared to study participants taking a placebo (“sugar pill”), patients who were assigned to take imatinib experienced more events that were a predefined sign of “clinical worsening,” were more likely to discontinue the drug during the trial and had a higher occurrence of brain bleeds (“subdural hematoma”). This combination of factors prompted the drug company to not pursue further testing of imatinib for PAH. However, despite these safety concerns, there were some patients who appeared to benefit from the treatment and did not experience any of these negative events. Had this study better tracked those who responded and those who did not, a follow-up study could have been beneficial, especially for those who had responded to the drug.
Before drugs are tested in humans, many early trials are conducted using animal models. Although some positive outcomes might be noted, the effect of medication on animals that have been given PH is not always the same experience as testing the same medication in humans. Differences in metabolism and side effects, which might not be apparent in animals, could impact the findings. The authors point out that animal studies do have some value; but should collect measurements frequently used in human studies. For instance, all animal studies should measure cardiac output and pulmonary artery pressure “to calculate pulmonary vascular resistance and assess effects on myocardial function [how the heart functions],” they assert.
Clinical trials also typically include a mixed group of patients who ultimately might not have the same exact disease, some with connective tissue disease-associated PAH, some with idiopathic PAH and some with minor defects in the chambers of the heart. Combining patients with different disease origins might not be appropriate or effective when it comes to developing targeted drugs, according to the authors. They suggest that identifying further genetic information about PAH could serve as a benchmark upon which researchers could enroll patients with more similar disease. This would, in effect, result in “personalized medicine.” They do point out that understanding genetic information about PAH is still in its infancy; but the cost of genome sequencing has become more affordable so obtaining this information is more feasible. Patient registries can also play an important role in identifying different groupings of patients we have not thought about before.
Dr. Lythgoe and colleagues conclude that early clinical trials have an ethical and economic responsibility to be designed in such a way that data can be interpreted effectively. Monitoring whether a participant responds or does not, and selecting study participants with common genetic markers, represents “a more intelligent approach” to developing new drugs for patients with PAH.
Read the Study, "Why Drugs Fail in Clinical Trials in Pulmonary Arterial Hypertension, and Strategies to Succeed in the Future."