Ethical examination of clinical trials. Necessity and absence of necessity

Not all studies involving people require a prospective examination or approval of an ethical committee. There are six categories of research that, although conducted with the participation of people, are exempted from the requirements of part 46 of section 46 of the CFR and the examination of the ethics committee. The general basis for these six categories is that research does not expose people involved in it to physical, social, psychological or other risks, except for those that are possible in daily life.

One example is the examination of available medical documents (for example, samples of biological material or disease histories) if these resources are publicly available or if the information is recorded by the researcher in such a way that the study participants cannot be identified directly or through the identifiers assigned to them.

However, many clinics have a stricter policy regarding the use of case histories and biomaterial samples for research, and researchers should be familiarized with the relevant policies of the institution.

In the United States, studies are often conducted according to surveys and questionnaires. Such studies may be exempted from ethical review if the information disclosed, if disclosed outside the scope of the study, does not subject the study participants to the risk of criminal or civil liability, or harm the person’s financial position, ability to seek employment or reputation.

Thus, questionnaires and questionnaires containing questions about illegal behavior, such as drug use, domestic violence or other confidential matters, such as sexual behavior and other particular behaviors, cannot be exempt from examination.

Before the beginning of the test, researchers should be familiarized with the requirements of the institution for obtaining an exemption from ethical examination.

The minimum risk means that “the probability and degree of expected harm and discomfort resulting from the study do not exceed the likelihood and extent of harm and discomfort in daily life or during routine medical or psychological examination or tests” (45 CFR 46.102)). The definition of minimal risk is necessary since in the examination by the ethics committee under accelerated review procedures, a certain minimum risk is allowed as a result of research activities. The accelerated process of examination was introduced with the aim of streamlining and accelerating the examination by the ethical committee of some research activity with minimal risks.


A new drug for the treatment of migraine may appear in Europe

The Expert Council of the European Medicines Agency recommended that regulatory authorities approve the preparation of galcanesumab, developed by the American company Eli Lilly for the treatment of a migraine.

Clinical studies show that the drug is effective in reducing the number of attacks of a headache. Galceanumab is a monoclonal antibody specific for the CGRP protein, which plays an important role in the development of a migraine and cluster headache. The injection drug is intended for self-administration by the patient at a frequency of once a month.

In addition to Eli Lilly, Amgen, Teva and Allergan are involved in the development of CGRP-specific drugs. So, last week Teva received a positive decision from the US FDA for its drug for the treatment of a migraine. The decision of US regulators on galcezumab will be announced at the end of this month.


The drug for the treatment of autoimmune skin disease received the status of “breakthrough therapy”

The US Food and Drug Administration (FDA) assigned the status of “breakthrough therapy” for the oral drug of JANUS-kinase 3 inhibitor class (JAK3) held by American pharmaceutical company Pfizer. The drug is designed to treat focal alopecia, a chronic autoimmune skin disease that causes hair loss on the scalp, face or body.

Assigning the status of “breakthrough therapy” for the treatment of focal alopecia was based on positive results of Phase II clinical trials. The status will speed up the development and evaluation of the product.

Millions of people suffer from focal alopecia all over the world. The consequences of the disease lead to deep psychological problems. Despite this, effective FDA-approved drugs for the treatment of condition are absent. The JANUS-kinase 3 inhibitor held by Pfizer can help to meet this critical medical need.

Pfizer also works with the European Medicines Agency under the clinical development program PF-06651600.

Focal alopecia is an autoimmune disease when immune cells attack healthy hair follicles causing hair loss.


Why do all pharma industry stakeholders must collaborate and encourage patients to share their personal data?

Currently there is an increasing concern regarding personal data protection. For example, the website of MyHeritage DNA – the company which offers one of the most affordable DNA test kits and which has built one of the best systems for combining genetic results with genealogy research – was hacked. As a result, 92 million of personal accounts were accessed by hackers. MyFitnessPal app suffered even more: 150 million accounts were breached.

However, when your email is breached you can just quickly change the password but when it comes to health data breach everything is not so easy: you cannot alter your DNA as you can alter your email password. That is why it is non-surprising that the question how personal data will be used and who will have access to them is a major concern for public. Due to this fact, people are trying to minimize the amount of personal data they share. However, data are the lifeblood of research and development. So what will be the consequence of this unwillingness to share personal data?

Pharma needs access to personal data such as data on MyHeritage (together with other databases) in order to find solutions for global health problems. So if patients still want to read news about breakthrough in personalized medicine or finding a new treatment for Alzheimer’s disease, they must be encouraged to share their personal data for the “greater good”. However, patients shouldn’t worry about the risk that their data may be breached and accessed by a third person.

One of the possible solutions is delivering the information to the public. People should know that we all need to share our personal data voluntary so that to contribute to global science. For instance, Veritas Genetic can sequence a person’s DNA for $999 and put these data in the mobile app. A person can share these data with his trainer but this information would be much more valuable if researchers seeking treatments for disease have an access to it too. Encouraging people to share their personal data is a difficult task but it is urgent. Therefore, all stakeholders need to share experience and work together. This collaboration should start from increasing public awareness of how their personal information could benefit research, to establishing a secure platform to store it. Needless to say, that contribution from key world regulators such as FDA and EMA will be required.



Why people aren’t interested in being part of clinical trials?

According to a recent national survey of consumers and physicians conducted by Memorial Sloan Kettering Cancer Center, only about 35% of people would consider taking part in one of clinical trials.
Finding participants is critical, so that trials are large enough to show that a treatment really could work on a large population. Shortages of participants can often make it hard to continue trials or get them underway in the first place.

Dr. Paul Sabbatini, an oncologist at MSK, told Business Insider that the low level of interest surprised him. With more information available through the internet, he had thought that there would be much more access to the trials.
“We had thought that people would be more familiar but that wasn’t found to be the case,” he told Business Insider.
It’s not just concerns about the safety of an experimental medication that stops people. Other barriers people cited were concerns about cost, and insurance coverage, and that they’d be receiving the placebo instead of the actual drug.

Sabbatini said that for the most part, these are actually misconceptions about how clinical trials are run. Other than location of the trial being a concern, he said, the other items don’t really require changes. Safety is closely monitored, most trials don’t have placebo arms (for example, many will opt to compare the drug to an approved treatment), and most don’t have increased costs, Sabbatini said.
Having a better understanding of what clinical trials are, and what participating in one actually entails, is key to changing these perceptions. It’s particularly important as the role of clinical trials, particularly in cancer, shifts from “last resort” treatments.

Instead, it’s becoming more common to alternate between one established treatment to an experimental one when it’s time to change treatments. Communicating this shift will be critical to getting the right people to enroll in the trials.
“We did this because we know that one big way forward is education, and that’s something we can all do,” Sabbatini said.


Cancer cells hide mutations in the years before the development of a tumor

Genetic changes in cancer bone cells can appear in the years before the cancer starts to grow. The discovery may help to prevent the development of this dangerous disease which appears usually in childhood or adolescence. The results of the study are published in Science journal.

For the treatment of any type of cancer it is very important to detect the disease at its early stage. In case of bone cancer and particular Ewing’s sarcoma it is even harder to diagnose the condition than usually because of extremely fast growing of bone sarcomas and early spreading of metastases (they form secondary tumors in other tissues of the body). The results of the latest study give a chance to “catch” sarcoma  before the tumor in fact begins to form.

Two genes of cancer bone cells called EWSR1 and ETS are known to fuse into one gene. However, scientists have not reveal the timing and the reason of fusion before. According to a new study, the genome of more than 100 cancer bone cells has been observed resulting in this mutation has been found to have occurred a few years before the first signs of a tumor appear.

The researchers have found that the fusion of the two genes called EWSR1 and ETS is not the essential genetic change in cancer cells. In 42% of cases there are violations of varying complexity in other important sites of the genome. Moreover, the more these violations were complex , the more the cancer cells  became aggressive, the more strict measures were necessary for destroying them. According to the study, the discovery will help doctors to select the more effective treatment for each patient.

X7 Research will take part in the annual BIOTECHMED forum 2018

Dear colleagues, our company X7 Research will take part in the annual BIOTECHMED forum!

From 9 to 11 September 2018 in Gelendzhik the third forum will be held – BIOTECHMED. The event will traditionally take place with the support of the Ministry of Health of the Russian Federation, the Ministry of Industry and Trade of the Russian Federation, the State Corporation Rostek, and the Administration of the Krasnodar Territory. The strategic partner is JSC “National Immunobiological Company”, the general partner of the Russian Export Center. About 1500 people will take part in the forum.

The main themes of BIOTECHMED 2018 will be: digital healthcare, fighting cancer, export of medical products. One of the key topics of the forum is the development and realization of the potential of the Russian pharmaceutical, biotechnological, medical and cosmetic industries.

We will be happy to meet you at this event!

FDA warning letter to the Indian drug manufacturer Goran Pharma

FDA has published a warning letter to the Indian drug manufacturer Goran Pharma after conducting an inspection. GDA has revealed non-complying with the principles of current good manufacturing practice (CGMP) as they have found serious drawbacks such as inadequate raw material quality control (identification of active ingredients and excipients from various suppliers), the absence of batch record reviews, problems with equipment design and lacking an air handling system as well as control of temperature and humidity in the manufacturing and warehouse areas.

Firstly, FDA indicated the raw materials which were used for drug manufacturing did not undergo quality testing. The manufacture had only supplier’s analyses certificates but did not check if they were valid. Therefore, there is a risk that these materials may be contaminated and using them may result in fatal poisoning for patients.

Secondly, the batches they had were released without reviewing all production and control records. Moreover, they were transported without prior microbiological testing.

Some problems were also found in the manufacturing area. Thus, in the equipment which was stated to be sterilized, they have found piping with dead legs. FDA suggests that this fact may lead to biofilms formation.

Areas for drug filling, packaging and storage were lacking an air handling system as well as control and monitoring of temperature and humidity in the manufacturing and warehouse areas. For example, in summer temperature in these premises could go up to 50°C.

As a result of the inspection, FDA has recommended the manufacturer to employ a consultant so that to correct the deficiencies revealed.

FDA statement on probiotics

On the 16th of September there has been published a new statement by FDA Commissioner Scott Gottlieb, M.D. This time the statement revealed the problem of regulating the market of products containing microorganisms. Nowadays as never ever before consumers all over the world know the idea of “good” or “helpful” bacteria which are supposed to help them to treat or prevent different diseases. The key role of FDA here is to set apart science and science fiction of this evolving field.

It is widely known that certain illnesses such as bacterial infections and their treatment with antibiotics may disturb the balance of normal microbiota in the human’s body. Microbiota is an aggregate of all microorganisms which live in our body. There is some evidence that the content of microbiota might affect the way the patient responds to certain treatment even cancer treatment. There are also preliminary data confirming that some microorganisms or “good bacteria” if administered preventively can help to prevent some illnesses.

For instance, scientists are investigating whether giving some probiotics may help to prevent necrotizing enterocolitis – a serious pathology in premature infants – as it is known that systemic infection underlies it’s pathogenesis.

In 2016 FDA released a guidance where the explanations on how scientists investigating probiotics as potential drugs can meet the manufacturing requirements needed for early clinical trials commencement. Later FDA has continued to put its efforts in improving the methods of studying the efficacy and safety of these products.

It is necessary to mention that by this time FDA has not approved any probiotic as a live biotherapeutic product, a biological product except a vaccine containing live organisms. There are lots of FDA-regulated foods, including dietary supplements which contain probiotics, which are legally available to consumers, however, it is illegal to sell them as products which may cure or prevent any diseases.

Due to the increasing interest in this field FDA together with the National Institutes of Health will conduct a workshop on the problem of microbiome-based products on the 17th September. One of the main aims of this workshop will be to discuss the potential of these products to prevent or cure different illnesses. What’s more, it is planned to discuss the ways of advancing regulatory rules in this sphere on order to be able to assess all these products properly. FDA recognizes the potential benefit of such products; however, some associated risks have also been identified. Therefore, it is necessary to ensure that consumers have enough information on these products before making a decision whether to buy them or not.


III and IV Phases of clinical trials

III Phase of clinical trials

If the drug is effective and safe in Phase II, it is examined in Phase III. Clinical Phase III trials are carefully controlled studies designed to determine the safety and efficacy of a drug under conditions close to those in which it will be used if it is approved for medical use.


  • determine the short-term and long-term safety / efficacy ratio for dosage forms of the active ingredient
  • determine its general and relative therapeutic value
  • Specific characteristics of the drugs
  • Investigate the profile and varieties of the most common adverse reactions

Usually, the studies have a comparative design in relation to the existing standard therapy (or placebo in the study of a new class of drugs).

Depending on the objectives of the specific study, controlled studies with placebo, reference medication or standard treatment are carried out at this phase. Tests can be either blind or open. Can be carried out in this or that design.

IV Phase of clinical trials

Conducted after the drug was registered for certain indications and becomes available through the retail network. These are the so-called post marketing trials, are conducted on a very large number of participants and are used to determine new modes of drug intake, identify new side effects, etc., provide more detailed information about the safety and efficacy of the drug.


In phase IV clinical trials, the efficacy and safety of registered drugs are studied or clarified within the limits for which medical use is permitted.

If a question arises about a new drug form of the drug, it is decided through Phase III.

Phase IV studies can be used for:

  • Improvements in drug dosage schemes
  • different terms of drug treatment
  • interaction with food or other medicines
  • comparative analysis with other standard courses of treatment
  • use of the drug in other age groups or in patients of other categories
  • effects of long-term effects of the drug on survival (decrease or increase in mortality)
  • long-term results in patients of different groups

IV phase is sometimes confused with postmarketing surveillance – monitoring the safety of registered drugs. Part of the IV phase trials is included in the monitoring process when they are observational in nature and are not experimental. In fact, Phase IV tasks include the study of effectiveness in addition to safety.