what you should know about clinical trials

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Virtually every medical treatment available to modern humans, fromdrugs to devices to surgical procedures to diagnostic technology, stems from a single source: Research


Medical Treatment

Better known as clinical trials, clinical research seeks to expand medical knowledge through the study of human volunteers (called participants).

Clinical Research


Clinical trials help to take the guesswork out of health care. To illustrate why this is important, you need only consider how “bloodletting,” or the practice of letting the “bad blood” out of patients, was a common medical treatment into the 19th century.


Clinical Trials

Doctors also once used brutal and ineffective treatments such as trepanation (boring holes in the skull) and mercury-containing elixirs. Source: History


Methods

http://www.history.com/news/history-lists/7-unusual-ancient-medical-techniques

Controlled clinical trials, by finding out answers to specific medical care questions, eliminate much of the ignorance and wishful thinking that defined pre-20th century medicine.


Pre-20th Century Medicine

Indeed, clinical trials were one of the primary drivers of skyrocketing human lifespans in the 20th century, and they remain a key component of our ever-improvingknowledge of medicine.


Lifespan Improvement

Your participation in a clinical trial can help to nudge medical knowledge ahead even further. In fact, there are many benefits to taking part in clinical research. There are some risks, too. But before delving into these pros and cons, a bit of background information is in order.


Volunteer

The world’s first clinical trial was performed by a military leader, not a doctor, and published in a religious text rather than a scientific one.


First Clinical Trial

The Bible records the story of how King Nebuchadnezzar, ruler of the Babylonians, ordered his people to eat only meat and drink only wine in order to keep up their strength. Several young men of royal blood objected to the king’s directive, preferring a vegetarian diet. Nebuchadnezzar allowed these men to consume only legumes and water for 10 days.


At the end of the experiment the king judged that the vegetarians appeared better nourished than the meat-eaters, so he let them continue with their dietary habits. Source: Bhatt


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149409/

Nebuchadnezzar’s experiment, however, lacked many of the characteristics of modern clinical research.


Trustworthy Trial ?

For starters, the experiment was subject to selection bias, as it was not undertaken with a random sample of all vegetarian Babylonians. Only royal young vegetarians were part of the experimental group, which made it impossible to control for variables such as gender and socioeconomic status. There was no way for the king to know whether diet or something else (perhaps the relative privilege of the young men) accounted for the seemingly-better health of the legume eaters.


Nowadays, clinical studies have much more rigorous inclusion criteria. Inclusion criteria describe characteristics that qualify prospective study subjects. They include things likegender, age, the type ofdisease being treated, and other known medical conditions. For example,the inclusion criteria for a study of high blood pressurewould be a diagnosis of highblood pressure. Studies also have exclusion criteria.Source: AHRQ


Criteria

http://effectivehealthcare.ahrq.gov/index.cfm/glossary-of-terms/?termid=34&pageaction=showterm

Another shortcoming of the meat eatervs. legume eater experiment was that there was no reliable measure of health among the participants. While the young vegetariansmay have “appeared” to be better-nourished,this conclusion was based on nothing other than the king’s opinion.


Reliable Measures

Modern clinical studies measure outcomes more rigorously with what’s known as endpoints. While some endpoints (including quality of life) are subjective, most are objective (i.e. “tumor shrinkage,” “progression free survival,” “disease free survival,” etc.). Statistical evidence, based on a predetermined algorithm, lends further weight to study outcomes.Sources: National Breast Cancer Coalition,The Hastings Center


Endpoints

http://www.breastcancerdeadline2020.org/breast-cancer-information/understanding-research/outcome-measures-or-endpoints.html

http://www.thehastingscenter.org/Publications/BriefingBook/Detail.aspx?id=2164

Yet another issue with Nebuchadnezzar’s experiment was the lack of a proper control group. A control group serves as a baseline measure compared to the experimental group. It allows researchers to eliminate and isolate variables in order to more accurately measure study results.Source: Explorable


Isolate Variables

https://explorable.com/scientific-control-group

Technically, Nebuchadnezzar did have a control group(the meat eaters). The king, however, was not merely comparing meat-eaters with legume-eaters (the experimental group), because the former group drank wine and the latter drank water. If he’d designed an experiment where one group consumed water and meat and theother water and legumes, the results would have been more telling.


Nowadays, control group participants might receive a placebo (an inactive product that participants believe is the test product, but which doesn’t have any treatment value), or an active treatment (one that has already been shown to work).

Placebo controls determine whether a treatment works, while active controls determine how the experimental treatment compares to the existing treatment.

Source: NIH


http://www.nih.gov/health/clinicaltrials/basics.htm

A final—and arguably the most critical—problem with the early Babylonian study is the lack of randomization. Randomization means that participants as well as investigators do not choose which participants are in the experimental group and which are in the control group. Instead, they’re assigned by chance to one or the other. Randomization is done to avoid bias.

Sources: The Hastings Institute, Hannan


Avoid Biased Resulted

http://www.thehastingscenter.org/Publications/BriefingBook/Detail.aspx?id=2164

http://www.sciencedirect.com/science/article/pii/S1936879808001702

If Nebuchadnezzar had truly abided by modern clinical research standards, his trial also would have been single-blind or double-blind. In a single-blind study, the patients are not told what they’re being given, but members of the research team do know. In a double-blind study, neither the patients nor the researchers know what is being administered; only the pharmacist knows. As with randomized studies, blind studies seek to eliminate bias.Source: NIH



Despite its flaws, the Old Testament dietary study demonstrated how human experiment could impact public health.

Roughly 2,000 years would pass before Randomized controlled trials (RCTs), widely considered to be the “gold standard” of clinical testing, came into practice.


The Gold Standard

The first published RCTs appeared in the late 1940s. The results of these trials improved treatment of twomajor killers at the time: tuberculosis and malaria.These landmark studiesushered in a new eraof medicine.Source: Archives of Diseasein Childhood/BMJ


New Era of Medicine

http://adc.bmj.com/content/79/5/410.full

http://adc.bmj.com/content/79/5/410.full

Today, a clinical trial is defined as a multiphase study conducted by researchers on human subjects to test a medical treatment or prevention strategy. The medical treatment being studied could be a drug, a medical device, a surgical procedure, or a therapy. The goal of a clinical trial is to determine if a new intervention works and is safe.Sources: Collier, NIH


Safety and Efficacy

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2612069/


Clinical trials are conducted in phases, each with a differentpurpose, number of patients, and length of study.• Phase 1 trials test a drug/treatment in a small group (~20 to 100) of

patients in order to evaluate safety and identify side effects.• Phase 2 trials may include up to several hundred volunteers and last

for several months to 2 years. Safety is further evaluated and effectiveness is measured.

• Phase 3 trials last up to 4 years and recruit up to 3,000 volunteers. During this stage of experiment, the experimental drug/treatment may be compared with standard treatments, and more information on safety and efficacy are gathered.

• Stage 4 trials are post-marketing studies done after a drug/treatment/device has obtained FDA approval. They seek further information about risks, benefits, and optimal use.

Sources: NIH, FDA



http://patientnetwork.fda.gov/learn-how-drugs-devices-get-approved/drug-development-process/step-3-clinical-research

Well before human volunteers are recruited for any stage of clinical trials, basic, pre-clinical research begins in laboratories. Both cell studies and animal testing precede human testing. Source: Columbia University Medical Center


Pre-Clinical Testing

http://www.columbiasurgery.org/pat/research/info.html

Following laboratory work, the most promising experimental treatments are moved into clinical trials. The study sponsor, however, which could be a physician, a foundation, a federal agency, a pharmaceutical company, or another group or individual, must come up with a study protocol (a detailed plan of the study) that is reviewed, approved and monitored by an Institutional Review Board (IRB). Sources: ClinicalTrials.gov, NIH


https://www.clinicaltrials.gov/ct2/about-studies/learn


IRBs consist of physicians, researchers, and members of the community who ensure that clinical trials are ethical and that participants’ rights are protected. IRBs are federally regulated.Sources: ClinicalTrials.gov, FDA


Regulations


http://www.fda.gov/regulatoryinformation/guidances/ucm126420.htm

While the IRB may periodically review the research, day-to-day clinical testing activities are overseen by a principal investigator (PI), who is typically a doctor, and a research team consisting of doctors, nurses, and other health care professionals. Sources: ClinicalTrials.gov, NIH




Participants are also protected by the process of informed consent. An informed consent document explains how the study works as well as its risks and benefits. But even after a participant signs the document, they’re free to withdraw from the study at any time. The informed consent document is reviewed by an IRB. Source: NIH



Hopefully it’s clear to you at this point that clinical trial participants are not “guinea pigs” or lab rats to be done with as experimenters please. There are numerous safeguards in place to protect study patients, who are free to opt out of trials whenever they want.


Safeguards

There are, of course, risks involved with taking part in a clinical study. Then again, any medical test, drug, or procedure has risks. The specific risks of a given study are outlined in the informed consent document, and you’ll be given ample opportunity to ask questions about the study before providing your consent.Source: American Cancer Society


Informed Consent

http://www.cancer.org/treatment/treatmentsandsideeffects/clinicaltrials/whatyouneedtoknowaboutclinicaltrials/clinical-trials-what-you-need-to-know-answers-to-common-questions

The National Institutes of Health (NIH) recommends that prospective clinical trial participants consider two important risk factors:

• The degree of harm that might result• The overall chance of harm occurring

The most common risk is that of minor discomfort. Less frequently, complications require medical attention. Patients do—albeit very rarely—suffer significant, even fatal, complications.

Source: NIH


Factor The Risks


Aside from physical side effects, be prepared to sacrifice some portion of your free time as a volunteer. You’ll not only have to report to the study location (such as a hospital, university, doctor’s office, or community clinic) on a regular basis, but the study may continue for a year or several years. Source: ClinicalTrials.gov


Time Involved


And some studies might require you to take actions (like wearing a portable blood pressure monitor or other diagnostic/monitoring equipment) away from the study location. In some cases, hospital stays are required. There may be out-of-pocket expenses for test drugs or treatments.

Source: Mayfield Clinic


Other Commitments

http://www.mayfieldclinic.com/PE-ClinTrial.htm

To avoid unanticipated inconveniences, be sure to carefully read the informed consent document and ask the researchers how the study might affect your daily life.


Be Informed

As for the benefits of participating in a clinical trial, it depends somewhat on whether you are a healthy volunteer or a patient volunteer. Both types of volunteers play a vital role in medical research.


You Play a Vital Role

A patient volunteer is somebody with a specific health problem or who is at high risk to develop a certain health problem. Patient volunteers typically participate in clinical research to better understand, diagnose, treat, or cure their disease.

Source: Mayo Clinic, NIH


Patient Volunteer

http://www.mayoclinic.org/healthy-living/consumer-health/in-depth/clinical-trials/art-20046652


A healthy volunteer is somebody without a significant health problem who participates in clinical research. These volunteers help researchers to define the limits of “normal.” They are given the same test, procedure, or drug as the patient group and serve as controls for patient groups.

Source: NIH


Healthy Volunteer

http://clinicalcenter.nih.gov/recruit/volunteers.html

For patient volunteers, especially those with cancer or other potentially fatal conditions, participating in a clinical trial could provide access to new drugs or procedures that are more effective than existing ones. There is no guarantee, though, that the drugs or procedures will benefit participants.

Source: Harvard Medical School


Access to New Treatments

http://www.health.harvard.edu/blog/taking-part-in-a-clinical-trial-advances-knowledge-medical-care-201106162850

But even if your participation in a clinical trial doesn’t benefit you directly, it could benefit others. Healthy and patient volunteers alike can be proud that they are continuing the human tradition of better living through research that began with Nebuchadnezzar circa 500 BC and continues to this day.


Benefit Others

From life-threatening diseases like AIDS, cancer, and diabetes to annoying ailments like the common cold and hair loss to everyday concerns like wounds, cavities, and skin aging, clinical trials are in the works that may some day provide major medicalbreakthroughs.


Benefit Others

ClinicalTrials.gov lists approximately 170,000 studies taking place in all 50 states and in nearly 200 countries. To find one near you, perform a search. Once you find a study you’re interested in, ask your doctor for more information about the drug or therapy being studied.

Source: ClinicalTrials.gov


Where To Find Studies

http://clinicaltrials.gov/

http://clinicaltrials.gov/ct2/resources/trends

As you search for a clinical trial near you, keep in mind that each study has inclusion/exclusion criteria, and that participants must qualify for a study. You’ll find out whether you qualify after you schedule a pretrial screening. During the screening you’ll get a chance to speak with the investigators and ask questions.

Source: Mayo Clinic


Where To Find Studies

http://www.mayoclinic.org/healthy-living/consumer-health/in-depth/clinical-trials/art-20046652

To learn more about clinical trials, check out the following websites:

• The American Cancer Society• U.S. Food and Drug Administration• ClinicalTrials.gov• Mayo Clinic


http://www.cancer.org/treatment/treatmentsandsideeffects/clinicaltrials/whatyouneedtoknowaboutclinicaltrials/clinical-trials-what-you-need-to-know-toc

http://patientnetwork.fda.gov/find-out-about-clinical-trials


http://www.mayo.edu/research/clinical-trials