Simplifying oncology informed consent in clinical trials

Simplifying oncology informed consent in clinical trials

Current expectations are that by 2030 the annual new cancer cases will reach 22.2 million people. There is an urgent need of new more efficient therapies to tackle raising cancer cases. Oncology clinical trials are part of the process to get new anti-cancer therapeutics on the market; however participation in clinical trials is low. According to the data for patients with colorectal, breast, lung and prostate cancer only 5% of the adults participate in clinical trials (less than 1 in 20 patients). While reasons for not willing to take part in research can vary data shows that up to 40% of the patients do not understand the inform consent information. [1]
Everyone involved in oncology clinical research is aware that inform consent could be a lengthy document with overwhelmingly many details, legal and regulatory language which is mandatory to be included, and extensive list of adverse events that put off patients.
International group of oncologists (Aide et Recherche en Cance´rologie Digestive (ARCAD)) has decided to tackle the issue by suggesting a new format for the inform consent form, which they consider will provide more clear information and expectations to patients.
What do they propose?
  • Separate inform consent into parts with leading part consistent of 1200-1800 words (3-5 pages), which includes: study title, reason for conducting research, brief description of the treatment and possible alternatives, frequency of the visits and examinations which are not standard of care, potential risks and benefits of the participation, clinically significant adverse reactions.
  • Supplementary part, which is 2000-3000 words (5-7 pages) that will include more details on adverse events, regulatory and legal requirements and other information.
  • Less information on risks – the authors suggest that as the treatment is new patients should be provided only with risks which are identified so far for the specific anti-cancer compound and avoid speculations.
  • Less adverse events – the authors explain that while there is no guidance regarding adverse events from FDA, EMA has recommendations and that only relevant adverse events and their frequency are included in the leading part. Additional adverse events could be listed in the supplementary part.
  • Life expectancy to be included – the authors believe, that although many oncologist may be reluctant to discuss life expectancy, that information needs to be included in the inform consent. They argue that this is important part that will help patients make the right decision. According to them some patients may decide against participating in a clinical trial if there is no relevant for them change in life expectancy.
Starting the discussion about the inform consent issues and providing recommendations is a major step in the right direction. The international medical and research community needs to adopt a new approach to empower patients to participate in clinical research. Although the consent form is just one part of a major challenge, it is an important part that needs to be addressed.
Source
  1. A step towards the harmonization of clinical trials inform consent forms
  2. A need to simplify informed consent documents in cancer clinical trials. A position paper of the ARCAD Group
Published on 3 October 2017
Author: Olga Peycheva, Director at Solutions OP Ltd. 
Olga has been working in clinical research since 2005 and has extensive experience in Eastern and Western Europe
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Review: Clinical trials and restricted medications

Review: Clinical trials and restricted medications

During my recent work I came across 2 cases of usage of restricted medications in patients participating in clinical trials. In both cases restricted medications were prescribed by GP or physician at local hospital without realising that patients should not take these medications. Just to put your mind at rest both patients are well, but what happened is something that everyone in clinical research should be concerned about.
But let’s start with what is restricted medication and why such medications exist?
All medications are metabolised in specific parts in the human body (in most cases liver is involved) and sometimes some medications can influence (increase or decrease) the plasma concentration of other medications. This could be potential safety issue for the patient as they could be exposed to overdose or lower than the required therapeutic dose. So it is understandable that such medications would be considered “restricted”. This is, of course, the simplest explanation.
Why restricted medications are very important in clinical trials?
As we know clinical trials drugs are newly developed compounds and there are lots of unknown about them. While they are in clinical trials it is important that patients do not take “restricted medications”, which could affect the plasma concentration of the study medication because this could be significant safety issue.
Then how these 2 cases happened and patients were prescribed restricted medications?
The discussion below is relevant to UK and I have to admit I am not familiar how health care systems around the world operate. In a perfect world all health care providers will have access to patients’ electronic medical records and they will be able to obtain the most up to date information. Unfortunately the world is not so perfect and each health care provider in UK has their own EMR or paper records that other providers do not have access to. This means that, more or less, we rely on patients to provide adequate information to different health care providers. However this is not a solution to the problem because patients cannot be expected to be able to explain what medications they should not take.
How to avoid “restricted medications” to be prescribed to patients on clinical trials from third parties?
The only possible option that the research team has is to ask their patients to contact them if they have medications prescribed by GP or local hospital so that they can advise them if they can take them. Although this again puts the focus on patients communicating to different providers this is still less complicated solution to the problem.
What is the big safety issue?
While patients participating in clinical trials are monitored closely and although such cases are not unusual research teams are able to react adequately to guarantee patients’ safety. The question is who is monitoring all these licensed medications on the market that have restricted medications too?
Published on 
2 May 2017
Author: Olga Peycheva, Director at Solutions OP Ltd. 
Olga has been working in clinical research since 2005 and has extensive experience in Eastern and Western Europe.
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Analysis: Clinical trials in rare diseases have their rare problems

Analysis: Clinical trials in rare diseases have their rare problems

Before we can start discussing the issues with conducting clinical trials in rare diseases we can clarify what type of conditions will classify as rare diseases. Often rare diseases include genetically determined diseases which affect small part of the population. And although we say “small part of the population” it actually includes millions of people around the world. It is important to mention that some of these rare diseases do not have any treatment options at all and physicians have to adapt current standard of care practices.
In the recent years rare diseases have gained popularity in clinical research as part of the personalized care approach and now there are more efforts in finding treatment for some of them.
What are the challenges in setting up rare disease clinical trials?
  • Finding the right hospital and the right physician – There are limited hospitals and consultants who are qualified to conduct clinical trials in rare diseases.
  • Finding the right patients – Another challenge is to reach out and find patients with a specific rare condition who would be interested to participate in research.
  • Setting the right timelines and expectations – Making sure the study will recruit the required amount of patients in a specific timeline could be a significant challenge.
But challenges exist not only for Sponsors but also for hospitals participating in clinical research.
What are the challenges for hospitals with rare disease clinical trials?
  • Majority of the hospitals may not be able to run such studies due to lack of experience, patient population or qualified consultants.
  • Financial loss – Setting up study and allocating resources for clinical trials is the same, however expected low recruitment rates (1-2 patients) may not justify the efforts from financial point of view.
  • Resource issues – The low recruitment rates will require even more resources to identify patients. This may jeopardize the efforts of the clinical trials team to set up other studies.
  • Loose study timelines – This is another significant issue for hospitals. Not knowing the exact close time for the clinical trials make it difficult to plan other studies and commit recourses elsewhere.
  • Limited access – Having 1 or 2 potential patients for a study may not be very attractive to hospitals which would prefer more patients to have access to new treatment.
There are new obstacles with increased popularity of rare diseases and they will need to be addressed by the research community in a way that it will be favourable for both, Sponsors and research teams. Although all challenges with this type of clinical trials their popularity is surely a good news for patients and will bring new treatment options.
Published on 
3 April 2017
Author: Olga Peycheva, Director at Solutions OP Ltd. 
Olga has been working in clinical research since 2005 and has extensive experience in Eastern and Western Europe.
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What are the criteria for enrolling people with intellectual disabilities in clinical research

What are the criteria for enrolling people with intellectual disabilities in clinical research

It is generally accepted that people with intellectual disabilities are not considered in clinical research if the type of the disease could be studied with people without disabilities. The reasons are different: to protect that vulnerable population but also the ethical principles in clinical trials which require patients to be aware of the research and give informed consent.
However, this has its disadvantages because it limits the research and treatment options in diseases which are specific for people with intellectual disabilities.
In order to improve participation in clinical trials some countries have created requirements for research involving people with disabilities. The criteria in US, Canada, Australia, UK and EU include the following:
  • Recommendations for IRBs:
  • All IRBs considering proposals that involve people with disabilities should have at least 2 members who are familiar with this patient population and at least one of them should be member of the population, family member or representative of this population.
  • Creation of a specific standing panel (SSP): to review individual protocols that cannot be approved by individual IRBs and to set guidelines that would permit local IRBs to approve protocols that cannot otherwise be approved.
  • Recommendations regarding research design:
  • Appropriate subject selection: An IRB should not approve clinical studies targeting persons with mental disorders if such research can be done with other subjects.
  • Thorough justification of research design and description of procedures to minimize risks to IRBs
  • Thorough evaluation of risks and benefits to the recruited patients.
  • Recommendations regarding informed consent:
  • No person who has the capacity for consent can be enrolled without informed consent
  • For research protocols that present greater than minimal risk, an IRB should require that an independent qualified professional assess the subject’s capacity to consent.
  • A person who has been determined to lack capacity to consent must be notified about that determination before permission is sought from his legally authorized representative.
  • Recommendations regarding categories of research:
  • Different recommendations are in place for clinical research involving minimal risk, greater than minimal risk with direct benefit to the subjects and greater than minimal risk that don’t offer the prospect of direct benefit to subjects with the latest category often requiring approval by a SSP.
  • Recommendations regarding surrogate decision making
  • Prospective authorization can be given while a patient still maintains capacity to make decisions
  • A legal authorized representative needs to provide consent for patients who lack the capacity to consent by themselves
  • Special recommendations are in place regarding educational materials and the public of ethical issues related to the involvement of such persons as research subjects, and increased funding will be required to ensure compliance with these recommendations.
One of the main challenges in research with patients with intellectual disabilities is that it is difficult to standardize the outcome. Treatment responses could vary significantly between individual patients, groups and types of diseases.
Regardless of all challenges people with intellectual disability should be included in research where appropriate and possible because it could have very beneficial therapeutic effect.
Source
Health Care for People with Intellectual and Developmental Disabilities
Published on 
2 March 2017
Author: Olga Peycheva, Director at Solutions OP Ltd. 
Olga has been working in clinical research since 2005 and has extensive experience in Eastern and Western Europe.
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Review: How to select sub-investigators in clinical trials

Review: How to select sub-investigators in clinical trials

Working on clinical trials requires very high qualified staff and some of the most important resources when working in clinical research are sub-investigators. Sub-investigators are qualified consultants who have relevant experience not only in the disease area but also in clinical research. The role of the sub-investigators is to support the Principal Investigator in identifying eligible patients and perform medical assessments and medical decisions for their treatment. Selecting the right sub-investigators can guarantee the success of the study.
What are the challenges in identifying sub-investigators?
  • Workload – Majority of the experienced in clinical research physicians work on clinical trials already. They may be too busy to handle new studies.
  • Friends – Although selecting colleagues who are your friends may sound like the best option sometimes they may not have the research experience to work on clinical trials or may not be interested in research in general.
  • Different treatment opinions – Some consultants may have specific opinion on treatment and may not be enthusiastic with the study medication or device. If your sub-investigators do not feel comfortable with the new treatment this could seriously jeopardise recruitment efforts.
  • Establishing new contacts – Involving different hospitals or GPs could be challenging if there is no established relationship with them already and yet they may turn into a valuable partners. However, working with new team members always require extra supervision until the work relationship is settled.
  • Temporary staff as sub-investigators – Although it looks tempting to include registrars as sub-investigators and they can indeed be very helpful, you need to consider the amount of time they will spend at the site. If they are on 6 month rotation they may not be the best choice.
In order to evaluate if someone is suitable for sub-investigator it is important to have honest discussion with them and understand what motivates them. You need to set realistic expectations from the beginning and make sure your team of sub-investigators receives appreciation and respect for their work.
According to Spilker (1991) there are 11 motivators (1):
  • Enhance one’s career – This is especially applicable for academic research. The disadvantage of this type of motivation is that if the study is not successful this could demotivate the physician.
  • Participate in scientifically exciting research
  • Obtain medical benefits for one’s patients
  • Obtain new medical or scientific equipment provided by sponsor to enable trial
  • Obtain new staff to help with clinical trials
  • Obtain money that may be used for personal interest – this is applicable for countries where investigators are paid directly
  • Obtain money that may be used to conduct unsponsored trials of personal and professional interest
  • Publish scientifically and medically important journal articles – This may not always be an option with commercial studies
  • Develop a long-term relationship with you and your treatment team
  • Repay a favour – This could be very limited as opportunity for future work together
  • Be part of a team – This could be applicable for GPs and solo practices
Whatever the motivation of the sub-investigator is it is important to set clear expectations at the beginning and be open about the workload involved. Least but not last the Principal Investigator is responsible for overseeing the study at the site so you will need a plan to monitor the clinical trial.
Source
  1. A Manager’s Guide to the Design and Conduct of Clinical Trials
Published on 
3 January 2017
Author: Olga Peycheva, Director at Solutions OP Ltd. 
Olga has been working in clinical research since 2005 and has extensive experience in Eastern and Western Europe.
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