New Vulnerability Found in Major Human Viruses

New Vulnerability Found in Major Human Viruses

Picornaviruses include rhinoviruses and enteroviruses. Rhinoviruses cause millions of cases of upper respiratory infections (“colds”) yearly and contribute to asthma, and enteroviruses are responsible for millions of infections including cases such as meningitis, encephalitis, and polio. There are currently no antivirals that can be used for the treatment or prevention of any of the rhino- or enteroviruses.

To replicate, viruses must interact with host cells, and in doing so, often need to change shape; stabilizing the virus particle is therefore thought to be a promising strategy for preventing replication. In a search for potential antiviral candidates, the authors found a compound that stabilized a model picornavirus. They performed cryo-electron microscopy (cryo-EM) of the drug-virus complex to determine how the drug exerted its effect. Cryo-EM involves combining thousands of two-dimensional images to develop a highly detailed three-dimensional image of the target.

Although picornaviruses have been studied for decades, the authors discovered a previously unknown pocket, or indentation, on the surface of the virus, in which the compound had lodged, thereby stabilizing it against the kind of shape change that would allow interaction with host cells. The team then used the compound as a starting point to generate multiple variants of the antiviral molecule to maximize the activity against a broad range of picornaviruses.

A major challenge in developing antiviral medications is that viruses mutate quickly, changing in ways that make a once-useful drug ineffective. While it is possible that the newly-discovered pocket may also mutate to make picornaviruses resistant to therapies developed against them, the authors suggest the pocket may be crucial enough for viral replication that viruses containing mutant versions may be less viable, making the drug relatively “resistance-proof.”

Further work to develop these compounds into effective drugs is ongoing.

Source: rdmag.com

Blausen_0246_ColorectalCancer

Delays Lead to Late-Stage Diagnosis of Young People With Colorectal Cancer

“The rising incidence of colorectal cancer in young adults is concerning,” says Gurprataap Sandhu, MD, a fellow at the CU Cancer Center. “In addition to trying to identify the cause of this increase, it is crucial to diagnose these patients at an earlier stage to improve clinical outcomes.”

The results of the study found that there was a high incidence of advanced-stage cancer and prolonged rectal bleeding history before diagnosis in young-onset patients with colorectal cancer. More than half of the 173 patients presented with rectal bleeding before diagnosis. On average, 294 days passed between the first time the patient noticed rectal bleeding and the time they were diagnosed. By the time of diagnosis, 37.8 percent of the patients were Stage IV.

“Our results show that young adult patients present with a much higher rate of Stage IV colorectal cancer compared to patients who are older than years of age,” says Sandhu. “This is especially significant as Stage IV patients have a much worse prognosis and are typically incurable with a few exceptions.”

Traditionally colorectal cancer screening starts at 50 years of age. However, the American Cancer Society (ACS) dropped the recommended screening age for average-risk patients to 45 in response to the increase of early-onset diagnoses.

“The finding of prolonged bleeding prior to diagnosis was surprising. It is possible that the bleeding was attributed to hemorrhoids initially, leading to potential delay in seeking medical attention and ultimately diagnostic workup,” says Sandhu. “Patients and primary care physicians should be made aware of this finding in order to facilitate timely referral for a colonoscopy which may lead to earlier diagnosis, less advanced disease at diagnosis, and improved outcomes.”

More about early-onset colorectal cancer

Colorectal cancer diagnoses in young people (under 50 years old) have been increasing significantly in the last decades. The reasons behind this are unclear but theories include the rising obesity in children, a decrease in childhood physical activity, and changes in the microbiome due to exposure to antibiotics.

According to a survey conducted by the Colorectal Cancer Alliance;

  • 82% of young cancer survivors were initially misdiagnosed
  • 73% were diagnosed at a later stage
  • 50% felt their symptoms were ignored
  • 62% did not have a family history
  • 67% saw at least two doctors before being diagnosed

If caught early, the average five-year survival rate for patients with colorectal cancer is 90 percent. This drops to 14 percent if diagnosed at later stages.

Colorectal Cancer

Novel Vaccine for colorectal cancer Shows Positive Phase I Results

A new colorectal cancer vaccine showed positive results in phase 1 clinical trial to demonstrate that the approach is safe.

The patients treated had no signs of serious adverse events and samples of their blood contained markers of immune activation — an early indication that the vaccine could activate immune cells to fight colorectal tumors and metastases. Further tests to determine if the vaccine is effective at slowing tumor growth are forthcoming.

Colon cancer, especially in younger people, is on the rise and is currently the second-highest cause of cancer deaths in the US and worldwide. Surgery can cure the disease in many patients, but the prognosis is poor for those with recurrence of their disease. If it proves effective in larger-scale trials the vaccine, developed by researchers at Jefferson (Philadelphia University + Thomas Jefferson University), could train the patient’s immune system to attack the colon cancer that had already spread before the surgery.

“There is an urgent need to understand what fuels colorectal cancer growth, and to harness that knowledge for developing novel therapies. This pivotal study provides some of the first evidence that it may be possible to safely direct a patient’s own immune system to seek and destroy this cancer type. This is a true milestone– made possible through the scientists and clinicians in our colorectal cancer team working in synchrony”, said Karen E. Knudsen, Ph.D., EVP of Oncology Services and Director of the Sidney Kimmel Cancer Center — Jefferson Health.

In earlier preclinical work in mice, Jefferson researchers demonstrated how the design of their vaccine worked. Tumor vaccines have historically been developed against a sort of molecular sign-post for cancer. Because they come from normal cells, cancer cells share nearly all of the same molecules, making it difficult for the immune system to differentiate normal from cancerous. Tumor antigens are molecules that the immune system can recognize as different from normal. In colorectal cancer, one such molecule called GUCY2C was identified by Scott Waldman, MD, Ph.D., the Samuel M.V. Hamilton Professor and Director of the Gastrointestinal Cancer Program of the Sidney Kimmel Cancer Center — Jefferson Health.

The vaccine developed by the first author, Adam Snook, Ph.D., Assistant Professor in the Department of Pharmacology and Experimental Therapeutics, Dr. Waldman and others, works by activating the immune system against the GUCY2C molecule. By joining the GUCY2C molecule with a molecule that boosts the immune reaction called PADRE, and loading it into an adenovirus vector, the researchers engineered a vaccine that could specifically target the colon cancer.

The current clinical trial enrolled 10 patients with stage I or II colon cancer. Patients were given one dose and came back for blood draws 30, 90, 180 days after immunization. Patients experienced some discomfort at the injection site but reported no serious side effects of the vaccine. The blood samples showed activation of “killer T cells,” the immune cell type the researchers had expected. These killer T cells are responsible for finding and killing colon cancer cells that are responsible for causing cancer to come back.

“We are preparing for a phase II study that will begin recruiting patients this fall,” says Dr. Snook. “We used lessons learned in the first study to modify the vaccine to hopefully make it even more effective.”

Since starting the trial, the researchers found that cancers other than colorectal cancer also express GUCY2C, including gastric, esophageal and pancreatic cancer. These are actually among the deadliest cancers. In fact, together with colorectal cancer, these four cancer types account for 20 percent of all cancer-related deaths.

“The goal of the study to begin this fall is to show that version 2.0 of the vaccine is even better and that it may benefit a much bigger group of the overall cancer patient population,” says Dr. Snook.

Source: Jefferson University

ACRP All-Star challenge! The competition heats up! Go team hyperCORE!

hyperCORE wins ACRP- All-Star Challenge

hyperCORE International took first place in the inaugural ACRP All-Star Challenge for Sites during the ACRP 2019 annual conference in Nashville.

Vanderbilt University Medical Center took second place, and Sarah Cannon Research Institute placed third.“Congratulations to the team from hyperCORE International on their win,” says Jim Kremidas, ACRP Executive Director. “We also want to congratulate Vanderbilt University Medical Center and Sarah Cannon Research Institute for their second-and third-place finishes, respectively.”
During the ACRP All-Star Challenge for Sites, teams were asked to collaboratively solve problems presented in three real-world scenarios and to present to a panel of industry-leading judges. Scenarios were not provided in advance.
“Clinical research is all about collaboration and problem solving, and that’s what the ACRP All-Star Challenge is all about,” Kremidas adds. “Clearly, these organizations all should be commended for their ability to work together and collaboratively solve problems while exemplifying operational efficiency, teamwork, effectiveness, cost constraint, and communication.”
“We are incredibly proud of the highly talented professionals from our site/network companies who came together as a team to compete,” says Jeff Kingsley, CEO of IACT Health and COO of hyperCORE. “Announced just a week ago, hyperCORE brings together a group of already highly successful and professionalized research site businesses in a powerful new way, and we were beyond thrilled to see that power in action at the ACRP All-Star challenge.”
The ACRP All-Star Challenge will be held again in conjunction with ACRP 2020 in Seattle and will include a broader set of team and individual competitions.

SourceACRP

Diabetes

Novel Therapies Slow CKD Progression in Patients With Diabetes

Treatment options for patients with CKD are limited and often determined by the etiology of the CKD. RAAS blockade (ACE inhibitors or angiotensin receptor blockers) has so far been the only therapeutic intervention which has been shown to significantly affect CKD disease progression. However, SGLT2 inhibitors provide a much-needed breakthrough in the management of diabetic nephropathy. “We are glad that we now have evidence that we can help our patients with this medication”, explains Professor Carmine Zoccali, President of the ERA-EDTA. “850 million people worldwide are affected by kidney disease- a worrying figure, and one that continues to rise. In about one-third of these patients, around 280 million people, diabetes is the cause of kidney failure. For these patients we now have an effective therapy, the CREDENCE study [1] provides evidence that SGLT2 inhibitors add to the armamentarium for the treatment of diabetic nephropathy”

In the double-blind CREDENCE trial patients with type 2 diabetes and chronic kidney disease with albuminuria already on the standard renin-angiotensin-aldosterone blockade and baseline diabetic therapy was randomized to receive canagliflozin, an oral SGLT2 inhibitor or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000). The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes.

The trial had to be stopped earlier than planned because the study medication showed such an overwhelming beneficial effect. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (HR 0.66; 95% CI, 0.53 to 0.81; p<0.001). In addition, the relative risk of end-stage kidney disease was lowered by 32% (HR 0.68; 95% CI, 0.54 to 0.86; p=0.002). The treatment group also had a lower risk of cardiovascular death.

“Many people do not know that patients with chronic kidney disease are at a particularly high risk of many other health outcomes, especially dangerous cardiac complications. It is good to know that there is finally a treatment which not only reduces the risk of becoming dialysis-dependent but which also results in an improved cardiovascular prognosis and survival”, comments Professor Zoccali.

Only a day before the SONAR study [2] had shown that the risk of renal events in patients with diabetes and chronic kidney disease could be significantly reduced by atrasentan (an endothelin-receptor antagonist) in selected patients (those who had shown a response to the medication before they were enrolled into the study). A risk reduction of 35% in the composite renal outcome of end-stage kidney disease and doubling serum creatinine could be reached (HR; 0.65 [95% CI 0.49-0.88]; p=0.0047).

“All in all these two studies are fantastic news for patients with diabetic nephropathy. For years no new treatment option has proved to be safe and effective and thus no new drug could be introduced into clinical practice. Now we have two new treatments with different therapeutic targets, which we might even combine.

Source: www.rdmag.com

liver

A Tiny Cry for Help From Inside the Liver Could Lead to Better Treatment

With few good treatment options available, more than 2,000 Americans die of acute liver failure each year.
Now, new research points to a potential way to prevent that damage, but more importantly even treat it—as well as a possible way to better monitor the health of patients who have suffered from it.
In a new paper published in the Proceedings of the National Academy of Sciences, a team from the University of Michigan describe how a protein involved in one of the liver’s most basic functions also sounds the alarm when liver cells get hurt.
That alarm, and the help that it summons from the immune system, can help protect the liver from further damage, the researchers report. It can even spur the repair of a damaged liver after injury, says Bishr Omary, M.D., who led the research team.

Unexpected Function

Working with a team of U-M colleagues from many fields, Omary and former postdoctoral fellow Min-Jung Park, discovered an unexpected function for the enzyme CPS1, short for carbamoyl phosphate synthetase-1.
Normally, CPS1 plays a key role in breaking down ammonia, a waste product the body needs to get rid of. It does this in the mitochondria of the major cells of the liver, called hepatocytes.
A few years ago, Omary and his team discovered CPS1 in an unexpected place: the blood of animals and humans with acute liver injury. They showed that the amount of CPS1 in the blood served as an indicator of the extent of the damage—but also found that it left the blood quickly. That made it a potential early marker for recovery from liver injury.
In the new paper, they report that CPS1 is normally released into the bile but ends up in blood upon acute liver injury. They were surprised to learn where CPS1 disappeared to the inside of white blood cells called monocytes. There, they found, it performs a good deed.
“CPS1 that is cleared from blood reprograms monocytes to become anti-inflammatory and move to the liver,” Omary, a professor in the Department of Molecular & Integrative Physiology and the Division of Gastroenterology and Hepatology at the U-M Medical School, said. “This cytokine-like function, which is entirely unrelated to its usual enzymatic function, provides a mechanism for the protective effect we observed. It’s very exciting since it offers a potential pathway to developing new treatments.”

Piecing Together the CPS1 Puzzle

Park, now a research scientist in the College of Veterinary Medicine at Chonnam National University in South Korea, led the painstaking work of studying CPS1 in the blood, bone marrow, liver, and bile of mice, and working to increase its levels in the blood by injecting mice with an extra supply she generated in the lab.
The researchers gave this exogenous CPS1 to mice before they exposed them to levels of acetaminophen—the same common over-the-counter medication that millions of people take, and that holds the potential to damage the liver in high enough doses and in combination with other substances. Even when the mice received doses high enough to cause acute injury, those that received added CPS1 beforehand did not suffer major liver damage.
When the researchers injected CPS1 into mice after they received the high dose of acetaminophen, the animals’ livers showed significant signs of recovery.
“The amount of CPS1 released to blood naturally is not sufficient to cope with injury, which is why the boost becomes very helpful,” Park said. “In contrast, if too much is spilled to blood by the liver, then this means too many liver cells have died to have a chance to recover.”
Another lab-generated, or recombinant, form of CPS1 that did not have any ability to perform the usual ammonia-processing action worked as an anti-inflammatory just as well as the normal enzyme. So the researchers could tell that the effects were caused by its immune-triggering powers that they also demonstrated using additional sophisticated methods.

Next Steps

Omary notes that since CPS1 is a fairly large protein, any effort to use and understand its therapeutic capacity might be improved by determining which of its components are most important for triggering the anti-inflammatory response.
He and his team are working to assess exactly how it works in mice, and to determine if it ultimately can be used as a therapeutic in humans. However, he cautions that significantly more work will be needed to determine the feasibility of its human use.

Source:rdmag.com

Hypercore

FOMAT Medical Research Joint Venture Partnership with HyperCORE

HyperCORE International LLP is a super network of highly experienced and awarded clinical research site/network companies.  The members and their companies have over 100 years of combined experience in the Clinical Trial space. Combined, they have completed more than 6,000 studies, assisting to evaluate thousands of new drugs and treatments in more than 60,000 patients. Each member operates as an independent company; however, each integrates common functions to streamline business and clinical operations through harmonization and sharing of best practices.

HyperCORE is an industry leader, providing Phase I-IV clinical trial services. It’s the second largest, worldwide network of sites, with over 80 sites in five countries, and two continents. Its representatives are a combination of eight of the top leading clinical research companies in the world. HyperCORE aspires to centralize the main operations and innovative strategic partnerships with Sponsors and CROs. Its main objective is to innovate the existing inefficient model of Research Sites.

 Its primary goal is to modernize the highly fragmented and inefficient research site model by assembling the industry’s leading site networks under one moniker, facilitating exponential efficiencies.

 
“This is the realization of a vision several years in the making. I wanted to bring together a group of already highly successful and professionalized research site businesses in a new and powerful way. The magic lies within the mutual ownership model. This motivates and ensures we each bring the best to the table and work together in ways not possible before. Together, we can push the boundaries, leading the drive for further innovation, something that will resonate across the clinical research industry. By banding together in such an intimate and integrated way, we can accelerate the entire end-to-end process from feasibility to close-out. Its research accelerated!”  
                                                Mark Lacy, CEO of Benchmark research and CEO of hyperCORE.

hyperCORE’s founding partner members are:

  • Benchmark Research of Austin, Texas
  • Clinical Trials of Texas of San Antonio, Texas
  • DIEX Research of Montreal, Canada
  • FOMAT Medical Research of Oxnard, CA
  • IACT Health of Columbus, Georgia
  • LMC Manna Research of Toronto, Canada
  • Research Centers of America (RCA) of Hollywood, Florida
  • Wake Research of Raleigh, North Carolina

About FOMAT Medical Research:

 FOMAT Medical Research is a modified and improved version of a traditional Site Management Organization with a highly qualified research site network. We offer a wide range of solutions for Sponsors, Clinical Contract Organizations (CROs), and Sites throughout the Americas. We have over 10 years of experience participating in Clinical Research in phase II-IV in most therapeutic areas.

“We are excited to be part of this research site network. I strongly believe that we can change the existing business model through this innovative collaboration that creates a more efficient approach for our sponsors and patients”

Nicholas Focil, CEO FOMAT

pregnancy

What lifestyle and environmental factors may be involved with infertility in females and males?

A number of lifestyle factors affect fertility in women, in men, or in both. These include but are not limited to nutrition, weight, and exercise; physical and psychological stress; environmental and occupational exposures; substance and drug use and abuse; and medications.
For example, research shows that:

  • Obesity is linked to lower sperm count and quality in men.
  • Among obese women who have polycystic ovary syndrome (PCOS), losing 5% of body weight greatly improves the likelihood of ovulation and pregnancy.
  • Being underweight is linked to ovarian dysfunction and infertility in women.
  • Strenuous physical labor and taking multiple medications are known to reduce sperm count in males.
  • Excessive exercise is known to affect ovulation and fertility in women.
  • Research shows that using body-building medications or androgens can affect sperm formation.
  • Substance use, including smoking tobacco, using other tobacco products, marijuana use, heavy drinking, and using illegal drugs such as heroin and cocaine reduce fertility in both men and women.
  • Having high blood pressure changes the shape of sperm, thereby reducing fertility.
  • The type of underwear a man chooses is not related to his infertility.
  • Radiation therapy and chemotherapy can cause infertility in females and males. Those who have to undergo these types of treatments may want to consider fertility preservation.

NICHD research also shows that exposure to persistent organic pollutants and endocrine-disrupting chemicals (EDCs) in the environment can also affect male and female fertility.
Persistent organic is currently used or was formerly used in industrial processes and remains in the environment much longer than other chemicals. Animal studies suggest that exposure to certain persistent organic pollutants affects fertility. NICHD’s Longitudinal Investigation of Fertility and the Environment (LIFE) Study is examining whether exposure to persistent organic pollutants affects the length of time it takes for couples to become pregnant, a measure of fecundity. It is the only study to measure chemicals in both partners and to follow couples trying to become pregnant for 1 year.
So far, the study has found that certain kinds of organochlorine pesticides and many polychlorinated biphenyls (PCBs) were linked to increased time-to-pregnancy or decreased couple fecundity.

The study found that many chemicals only affected time-to-pregnancy when finding high levels in the male partner, whereas other chemicals only affected fecundity when detected in the female partner. Other studies have linked exposure to TCCD dioxin and select polybrominated diethers and perfluorochemicals to reduced fecundity.
EDCs alter the function of the hormonal system, key component of infertility. The LIFE study found that the EDC methylparaben affects fertility in women, while phthalates and the UV filter benzophenone-2 affect fertility in men.
Source: NIH.gov

Influenza

Mechanism to Form Influenza A Virus Discovered

Influenza A virus can only multiply within the cells of the body it infects because it needs to use the cellular machinery of the host. When infection occurs, the virus enters into the cell and releases its genetic material and some proteins. But these viruses have an unusual peculiarity: their genome is segmented into eight distinct parts. Thus, during virus multiplication, the eight parts of the genetic material are replicated many times. The formation of new viruses requires that these eight segments are assembled into the same viral particle, which implies a very precise selection out of thousands of molecules that are mixed. Where this selection is made was unknown until now.

The study of the team of Maria João Amorim reveals that the selection of the genetic material is made in viral-induced compartments called viral inclusions. The researchers found that these compartments are not delimited by a membrane, as the traditional organelles in the cell. Instead, viral inclusions are separated from the surroundings by a process called liquid-liquid phase separation. This process is similar to what happens with vinegar and olive oil when placed together. In this way, the genetic material of the virus is segregated and confined to a small space where it is easier to assemble the sets of eight pieces that form the genome.

“Our results pave the way for alternative therapies that could target genome formation or the place where the genome is formed,” Amorim said. The IGC researcher also explains that “this work is innovative because it is one of the initial observations that demonstrate that viral infections use phase separation processes.”

Phase separation in biology is a research area of increasing interest. Changes to this process cause but also the consequence of many diseases, mainly neurological diseases. The work published by the IGC team opens the door to investigate the role that phase separation plays in infections caused by influenza and other microorganisms.

Source:  dddmag.com

Randomized Clinical Trials

Clinical Trials at a Glance!

Read more about Clinical Trials, about their phases as phase I-IV, as well as their types as Randomized Clinical Trials.

Clinical trials are research studies performed in people that are aimed at evaluating a medical, surgical, or behavioral intervention. They are the primary way that researchers find out if a new treatment, like a new drug or diet or medical device (for example, a pacemaker) is safe and effective in people. Often a clinical trial is used to learn if a new treatment is more effective and/or has less harmful side effects than the standard treatment. Randomized Clinical Trials
Ra

Clinical Trials Types:

There are two main types of trials or studies – interventional and observational. 
Interventional trials aim to find out more about a particular intervention, or treatment. People taking part are put into different treatment groups so that the research team can compare the results.
Observational studies aim to find out what happens to people in different situations. The research team observes the people taking part, but they don’t influence what treatments people have. The people taking part aren’t put into treatment groups.
There are different types of trials within these two groups. This page has information about

  • Pilot studies and feasibility studies
  • Prevention trials
  • Screening trials
  • Treatment trials
  • Multi-arm multi-stage (MAMS) trials
  • Cohort studies
  • Case-control studies 
  • Cross-sectional studies

What trial phases are?

Clinical trials testing new treatments are divided into different stages, called phases. The earliest phase trials may look at whether a drug is safe or the side effects it causes. Later phase trials aim to test whether a new treatment is better than existing treatments.
There are 3 main phases of clinical trials – phases 1 to 3. Phase 1 trials are the earliest phase trials and phase 3 are later phase trials. 
Some trials have an earlier stage called phase 0, and there are some phase 4 trials done after a drug has been licensed.
Some trials are Randomized Clinical Trials. This means the people taking part are put into one of the treatment groups at random. Doing this means the results are more reliable.

Trial phases at a glance

Phase Number of people
taking part

 
Main aims of trial Is it
randomized?

 
       0 Small – often about
10 to 20 people
Testing a low dose of
the treatment to check it isn’t harmful
          No

1

Small – often about
20 to 50 people
Finding out about side
effects, and what
happens to the
treatment in the body
        No

2

  Finding out more about
side effects and looking
at how well the
treatment works
Sometimes
     3 Large – hundreds or
thousands of people
Comparing the new
treatment to the
standard treatment
        Usually
     4 Medium to large,
variable
Finding out more about
long term benefits and
side effects 
         No

Randomized Controlled Trials (RCTs)

Randomized Clinical Trials

Randomized Clinical Trials

A randomized controlled trial (RCT) is a way of doing impact evaluation in which the population receiving the programme or policy intervention is chosen at random from the eligible population, and a control group is also chosen at random from the same eligible population. It tests the extent to which specific, planned impacts are being achieved.

In an RCT, the programme or policy is viewed as an ‘intervention’ in which a treatment – the elements of the programme/policy being evaluated – is tested for how well it achieves its objectives, as measured by a predetermined set of indicators. The strength of an RCT is that it provides a very powerful response to questions of causality, helping evaluators and programme implementers to know that what is being achieved is as a result of the intervention and not anything else.

  • The simplest  Randomized  Clinical Trials (RCT) design has one treatment group (or ‘arm’) and a control group. Variations on the design
    are to have either:
    multiple treatment arms, for example, one treatment group receives intervention A, and a second treatment group receives intervention B, or
    • a factorial design, in which a third treatment arm receives both interventions A and B.

In situations where an existing intervention is in use, it is more appropriate for the control group to continue to receive this, and for the RCT to show how well the new intervention compares to the existing one.

In a simple Randomized Clinical Trials (RCT), the unit of analysis for the intervention and for the random assignment is the same. For example, when evaluating a programme that provides nutrition to individuals, individuals might be randomly assigned to receive nutritional supplements.
For both practical and ethical reasons, however, it is more usual to use a cluster Randomized Trial’s design, in which the unit of assignment contains multiple treatment units. For example, education interventions are usually assigned at the school level, although the intervention takes place at the level of the teacher, classroom or individual child, and effects are measured at the level of the child. Nutrition interventions, for example, can be assigned at the community or sub-district level. Given the kinds of large-scale programmes supported.

Source:  Unicef