When it comes to engaging with potential enrollees, many clinical trials fail to attain the numbers of participants required in order to conduct proper research. There are a plethora of reasons for this, from myriad rigid regulations to the general lack of awareness on the part of the patients looking for clinical trials. Companies such as TrialsLoop and Genospace are looking to provide services that open links between clinical trials and their participants that will benefit the medical community and, ultimately, the world we live in.
The Reviews Are In: TrialsLoop
A website launched earlier this month takes the phrase “placing power in the palm of your hands” quite literally. “Empowering Patients with Patient Experiences” is the motto of TrialsLoop, a website that allows participants in clinical trials to provide reviews of their experience. The website was launched in an effort to eliminate the mystery and confusion that can sometimes bog down the individual who is seeking information about clinical trials.
“We ask patients who are going through clinical trials to share their experience with other patients… who want to be a part of clinical trials,” says CEO and Co-Founder of TrialsLoop, Chance Curtis, in an interview with Clinical Informatics News. It’s helpful for prospective participants in clinical trials “to see the importance of participating and to see what exactly goes on behind the scenes,” he says.
Curtis has a personal reason in providing this service; he had an aunt that was diagnosed with breast cancer who had been fishing for clinical trials. However, she gave up her search for clinical trials due to lack of information. “If there was something available at that time for [participants in clinical trials] to use as an outlet and share [their] experience, I believe more people would be involved in clinical trials, and less clinical trials would be delayed because of [a lack of] recruitment,” Curtis says. “We don’t want people to feel as though there isn’t another option or they just aren’t informed by another patient’s voice.”
TrialsLoop is in uncharted territory with the launch of its site, as it allows the participants in clinical trials to have a strong presence in the clinical trials industry. “From what I’ve seen, this is the first website [that does this kind of thing],” remarks Curtis. The obvious question to ask, then: Why has it taken so long for a website that provides the kinds of services TrialsLoop does to be launched? Curtis points to an fear of unblinding clinical trials that has led to both rigid policies and “old, unwritten rules” that are currently in place in the sphere of the clinical trial community.
This concern has naturally led members of the medical field to be skeptical of the ambitions of TrialsLoop. TrialsLoop recently had the opportunity to outline a detailed plan of what the website hoped to accomplish to doctors and representatives in the clinical trials field. “Once we explained what we were actually doing, then they said, ‘This makes sense. This could actually help us in our own clinical trials,’” Curtis recalls. Though he admits that some representatives are not yet convinced, and prefer to sit back and see how people respond to the site.
The passive response of these representatives seems natural, as there are several kinks the website needs to work out. For instance, the problem of unblinding clinical trials is still a prominent one, and so far TrialsLoop’s answers to the issue are vague. “The only information that the public will see on our site is the patient’s summary of their experience,” Curtis explained in a later interview with Clinical Informatics via email.
“For example: ‘Dr. John Doe and his staff were beyond helpful throughout the trial. They educated me on the treatment in terms that I could understand. I would suggest that people be more involved with clinical trials and forget the myths that are being said.’”
When asked how he will ensure such reviews will follow such a pattern, Curtis responded, “By curating reviews we will ensure unblinding does not happen. There will be guidelines and directions for the patient to follow when leaving their summary review.”
TrialsLoop is confident in their product, saying the system they use is one that we use all the time. “Think of it as using a review the same way you would to make everyday decisions in your life,” Curtis illustrates. “Whether it’s going to restaurants, a tire shop, a dentist, anything. Anything in your life, before you go, you check and see what other people have to say or think about that business.” Keeping this in mind, Curtis believes that the humanistic, word-of-mouth approach to clinical trials will be of tremendous impact in the medical field. “This is an opportunity to bring [the review] concept over to clinical trials because clinical trials are important; we need them for the future of medicine. And if we don’t have the people to participate, then we can’t make the necessary advances in medicine that we need to become a great society.”
Matchmakers Of Medicine: Genospace
Yesterday, Genospace announced the launch of Trial Match, a mobile application that enables real time clinical trial matching based on molecular profiling and other clinical data at the point of care. According to Genospace, “less than 4% of cancer patients enroll in trials each year, more than 80% of trials fail to meet original enrollment timelines, and nearly 1/3 of trial budgets are spent on recruitment.” Genospace Trial Match hopes to improve those statistics with a mobile app that allows doctors and nurses to provide quick recommendations for their patients to clinical trials.
Genospace, which won the Best of Show Award at the 2014 Bio-IT World Conference, combines analytical capabilities with clinical data. The goal of the Genospace Trial Match is to match patients to trials in a mobile app. This new app allows physicians to bridge the gap between patients looking for clinical trials and sponsors looking for participants. Through Trial Match doctors are able to identify which patient fits the criteria of a given clinical trial and vice versa.
The concept of allowing patients and physicians in clinical trials to engage with one another is not a new mobile gem the Genospace team have discovered. However, Genospace is confident that its mobile app will stand out thanks its database of information. The sophistication of the matching database is what separates Trial Match from the competition, said Mick Correll, CEO of Genospace. The mobile app uses new EMR, molecular, or clinical trial information to provide recommendations for individual clients, as well as a rating recommendations based on the strength of the match. The search engine uses molecular data that harmonizes results useful to both the sponsors of clinical trials and the physicians who refer patients for those trials.
The process is simple enough. Nurses and doctors place their patient’s information into the enterprise application. Once this is completed, a sophisticated matching algorithm links potential trials with the qualifications of the patients. When matches are updated, the physicians receive notifications on their phone and can refer their patients in seconds. According to a statement from Genospace, once they receive the notifications, “physicians can set up appointments, email trials details to patients, contact trial principal investigators, or set reminders for follow up.”
Genospace is hoping that this new app will combine the complexity of clinical data with the speed and efficiency of a mobile app. If the app is everything Genospace hopes it to be, Trial Match could place the point of clinical trial care in the palm of one’s hand.
In short, clinical trials are a means for patients to have access to therapeutics ahead of everyone else, and for developers of therapeutics to assess whether the therapeutics are effective in an ethical manner. Developers of therapeutics are usually Pharmaceutical Companies, Biotech Companies, or even Academic Institutions such as Universities.
Let me explain this in a little more detail. First we use the word “therapeutics” because clinical trials are not only performed to test drugs, but also to assess “living drugs” such as stem cells, as well as to assess medical devices or even herbal remedies.
There are several types of clinical trials. One type is observational. In observational clinical trials, patients are assessed for particular characteristics without being administered a therapeutic. The type of clinical trials that we are interested in at trialsloop.com are called “interventional trials”. In these types of trials the “intervention” is a therapeutic that is aimed to better a patient.
It is important to note, that just because a patient is given a therapeutic, it does not necessarily mean that the patient’s medical conditions will improve. In some clinical trials, such as a Phase I trial, the optimal dose of a therapeutic is not known, therefore some patients may benefit and others may not. Furthermore, in Phase III clinical trials, although the optimal dose is known, some patients receive the treatment but others receive placebo. In double blind clinical trials neither the doctor giving the medicine, nor the patient receiving the medicine, know who is receiving placebo and who is receiving the treatment. Furthermore, in clinical trials it is not known whether the therapeutic actually will possess a beneficial effect. On the other hand, in some situations the effect of the therapeutic agent is so potent that the clinical trial is stopped and everyone in the trial is given the therapeutic because it would be unethical to deny patients something that works wonders.
In clinical trials there are classically four phases of development. The first phase is aimed at assessing the distribution of the drug in the patient, as well as potential safety issues with the drug. In the case of medical devices, it is difficult to assess distribution of the medical device in the patient but instead safety and ability to use the device in a reproducible manner is the main aim. In Phase II clinical trials, the potential efficacy of the intervention is assessed. In the case of drugs, the Phase I trial provides the optimum dosage that is safe but also possesses possibility of therapeutic benefit.
Let me give you a specific example. If a drug developer creates a medication for treatment of rheumatoid arthritis, the medication is usually aimed at blocking a specific molecule associated with rheumatoid arthritis. For example, one of the main molecules that causes rheumatoid arthritis is Tumor Necrosis Factor (TNF). This molecule has been shown in many studies to cause erosion of cartilage and inflammation of synovial joints (which are the causes of pain and degeneration in rheumatoid arthritis). Given that everyone in the field knows the importance of TNF in causing rheumatoid arthritis, many companies are developing drugs to block activity of TNF. Accordingly, TNF is referred to as a “validated target”. When our hypothetical drug developer discovers a drug that blocks TNF, they discover the drug by screening compounds or creating new compounds. TNF activity is usually tested in the laboratory by ability to induce certain changes in cells. When TNF is added to cells together with the test compound, if the changes in the cells are no longer present, it means that TNF activity has been blocked. This test is referred to in drug development language as an “assay”. Once an experimental compound has demonstrated activity in the “assay” it is called a “drug candidate”. The “drug candidate” is then tested in animals for safety.
Additionally the distribution of the drug in the body of the animal is assessed. This is important because firstly, one needs to know if the drug candidate when administered in a living system can reach the concentration needed to elicit the desired effect. In our hypothetical case, the desired effect is ability to block activity of TNF alpha. If this is indeed feasible, then the candidate is tested in animal models of the disease. In the case of rheumatoid arthritis, the animal model is termed “collagen induced arthritis”. Essentially this involves administering to mice a protein that stimulates the immune system to attack the joints. The animal gets essentially what is similar to the human disease of rheumatoid arthritis.
If a drug successfully is demonstrated to be safe in animals, as well as to evoke a therapeutic effect in animal models of the disease, then the developer of the drug applies to the regulatory agency (in the USA this is the Food and Drug Administration (FDA)) to begin a Phase I clinical trial. The process of application to begin a Phase I clinical trial involves filing what is called an “Investigational New Drug” IND application. For clinical trials in the first Phase, the drug developer has two main choices: they can use small concentrations of the drug and test it on healthy subjects, or they can use concentrations that they believe to be therapeutic and actually test the drug on patients with the disease. In situations where patients with the disease are treated the trial is sometimes referred to as a Phase I/II trial since it has the safety and drug distribution assessments of a Phase I trial, but also has efficacy endpoints of a Phase II trial.
In many situations Phase I clinical trials are dose escalating meaning patients are randomly placed into different groups and each group receives higher concentrations of the drug. So to address the comment I made previously, in some Phase I trials, because the optimal concentration of administration of the drug is not known, there is a higher chance of the drug not working in some of the patients as compared to if patients were in a Phase II trial in which the optimized dose of the drug is already known. Furthermore, the Phase III trial is essentially a validation of the Phase II in that it is performed at multiple independent institutions, and is double blind, meaning that neither the patient, nor the physician knowns whether they are administering drug or placebo. Once a drug passes Phase III the developer of the drug then usually applies for registration for sale of the drug.
By the process of running clinical trials, much is learned by the scientific and medical community. While clinical trials in some cases do not achieve the “endpoints” or outcomes that are desired, the information learned from trials is many times published in the peer-reviewed literature and provides the basis for future investigations.
The clinical trials process does not end when a therapeutic agent is approved for marketing. In some cases there is such a thing as a Phase IV clinical trial. These are clinical trials on drugs that are already approved but the trial seeks to evaluate certain characteristics of patients that are already taking the drug. For example, the diabetes drug metformin has been shown to have anticancer properties. A clinical trial of patients who are already diabetic but evaluating whether the patients have a reduced rate of cancer would be considered a Phase IV clinical trial.
One of the questions that is frequently asked regarding clinical trials is how patients are protected from possible adverse effects of the therapeutic agent that is being tested on them. This is an important question because in the past there have been disasters in clinical trials and in the process of drug development. Perhaps one of the most widely publicized disasters was the “Thalidomide Tragedy” in Europe, where a drug company created a pill to reduce morning sickness in pregnant women. Although the drug was approved and widely-used in Europe, when the company applied to the FDA for permission to sell it, the FDA noticed some strange abnormalities in the animal data. Dr. Frances Kelsey, then a junior person at the FDA, stubbornly refused to grant approval because of these abnormalities. Although initially being persecuted by her superiors for her stance, when reports of widespread birth defects were realized in Europe, she became a National Hero. Subsequent to the “Thalidomide Tragedy” numerous laws were put in place to ensure that animal toxicity data is required before drugs are allowed to be administered to patients.
In many situations the FDA requires that drugs be tested at the proposed therapeutic dose on a per kilogram ratio, as well as at higher doses. In fact, in some cases the FDA requires what is called “LD50”, which stands for “Lethal Dose 50”. For example, if drug X is believed to work at 1 mg/kg body weight, then the drug in given at 2, 4, 8, 16 etc mg/kg in animals until 50% of the animals die. This allows for determination of toxic doses and also what the mechanisms of toxicity are. Additionally, studies are required to determine ADME, which is Adsorption, Distribution, Metabolism, and Excretion. All of these are to ensure that as much has possible is known about the drug before it enters humans.
Condition : Neck Pain, Back Pain, Spasm
Category : Nervous System Diseases, Symptoms and General Pathology
City : N/A
Country : N/A
Description : The purpose of this study is to assess the effect of cyclobenzaprine hydrochloride (HCl)
extended release (CER) 15 mg once daily in subjects with muscle spasms associated with acute
painful musculoskeletal conditions.
Eligibility : Inclusion Criteria:
1. In the opinion of the investigator, the participant is capable of understanding and
complying with protocol requirements.
2. Signs and dates a written, informed consent form and any required privacy
authorization prior to the initiation of any study procedures.
3. Is experiencing for no more than 14 days cervical or lower back pain (as assessed by
the participant) due to muscle spasms (confirmed by the physician) associated with
acute, painful musculoskeletal conditions.
4. Is male or female and aged 18 to 50 years, inclusive.
5. Female participants require to be either 2 years postmenopausal or surgically sterile
by bilateral tubal ligation, hysterectomy, or bilateral oophorectomy, or, if
premenopausal, had to be using an approved contraceptive method.
6. Female participants of child-bearing potential must have a negative urine human
chorionic gonadotropin (hCG) test result for pregnancy at study entry.
7. After signing the informed consent form, the participant agrees not to make changes
to dietary, exercise, or smoking habits and not to enter a weight loss program during
his/her participation in the study.
1. Has muscular pain secondary to acute trauma or fractures (e.g., due to osteoporosis).
Such conditions could have been ruled out based on medical history, x-ray, or
2. Has received any investigational compound within 30 days prior to Screening.
3. If female, the participant is pregnant or lactating or intending to become pregnant
before, during, or within 1 month after participating in this study; or intending to
donate ova during such time period.
4. Has a history of drug abuse or recent (within the last 12 months) history of
excessive alcohol consumption defined as >2 drinks/day (>90 ml of 80 proof alcohol or
5. Has mild, moderate, severe liver impairment.
6. Is an immediate family member, study site employee, or is in a dependent relationship
with a study site employee who is involved in conduct of this study (eg, spouse,
parent, child, sibling) or may consent under duress.
7. Takes any concomitant medication including over-the-counter and herbal products for
muscle spasms. If a participant is taking such medications, the medications has to be
discontinued before starting the study.
8. Takes or took within last 14 days medications, such as:
1. selective serotonin reuptake inhibitors (SSRIs);
2. serotonin norepinephrine reuptake inhibitors (SNRIs);
3. tricyclic antidepressants (TCAs);
4. monoamine oxidase (MAO) inhibitors;
9. non-steroid anti-inflammatory drugs (NSAIDs);
10. topical anti-inflammatory medications
9. Has a history or clinical manifestations of significant medical condition, such as:
2. acute recovery phase of myocardial infarction;
3. arrhythmias, heart block or conduction disturbances;
4. congestive heart failure;
5. angle-closure glaucoma;
6. urinary retention;
7. increased intraocular pressure.
10. Has abnormal physical findings or a medical condition that might have placed the
participant at risk or interfered with the participant’s ability to participate in
11. Has any known condition or disorder that might have affected absorption of the study
12. Has a history of hypersensitivity or allergies to cyclobenzaprine and/or tricyclic
antidepressants or any of their components.
13. Has a history of hypersensitivity to any NSAIDs including salicylate sensitivity.
14. Has a history of thrombocytopenia.
15. Has a history of gastro-intestinal bleeding, cerebrovascular bleeding or other
16. Had active or history of recurrent peptic ulcer/haemorrhage (two or more distinct
episodes of proven ulceration or bleeding)
17. Has a history of severe renal impairment
18. Had a major surgery during the 6 months preceding study entry.
19. Has a language barrier or any other problems precluding good communication or
20. Has any reason to believe that he/she would not be able to complete the evaluations
needed in this study.
21. Has a known history of positive screen for hepatitis B surface antigen, hepatitis C
antibody, or human immunodeficiency virus (HIV) antibody.
22. Drug abuse in anamnesis.
Condition : Coronary Artery Disease
Category : Heart and Blood Diseases
Description : The primary objective is to determine whether IVUS- (vs. OCT-) guided BVS implantation is non-inferior to achieve a large in-scaffold minimal lumen area (primary endpoint) measured by OCT at 1-year follow-up.