Frequently asked questions

A clinical trial is a research study conducted in humans to answer specific questions about new therapies, vaccines, surgical procedures, or diagnostic procedures. It may also evaluate new ways of using known treatments, such as those used to treat cancer.

Clinical trials determine whether new drugs, diagnostics, or treatments are safe and effective. Carefully conducted clinical trials are the fastest and safest way to find treatments that help people.

After researchers test new investigative therapies or procedures in laboratory and animal studies, those with the most promising possibilities are moved into human clinical trials for further observational studies. Clinical trials are broken down into different phases.

During a trial, more information is gained about the potential treatment or experimental drug, its risks, how well it may or may not work, and aspects related to quality of life.

Several entities are involved in treatment trials—namely, organisations, institutions, and individuals who have a stake in the trial’s performance and results.

In addition to the researchers and patients at the crux of clinical studies, these typically include:

• Regulatory agencies, such as the European Medicines Agency (EMA) or the US Food and Drug Administration (FDA), govern the approval and regulation of new treatments

• Institutional review boards (IRBs) are tasked with confirming that ethical standards regarding patients have been upheld

• Sponsors, which run the gamut from academic institutions to pharmaceutical companies

• Healthcare providers who may use the new treatment with their patients, such as the National Cancer Institute and the National Institutes of Health

• Patient advocacy groups that represent patients’ rights and have a hand in promoting the development of novel treatments

Participating in a clinical trial isn’t without risk factors and inconveniences: volunteers may experience mild to severe side effects from experiential medications. Others who participate in randomised controlled trials may be given a placebo. Many clinical trials might also call for hospital stays, lengthier doctor appointments, and time-consuming medical instructions and procedures.

Fortunately, the rights of enrolled participantsare rigorously protected by federal government agencies, such as the Health Research Authority (HRA) and the Medicines and Healthcare Products Regulatory Agency (MHRA). Patient confidentiality is also assured through several safeguards.

Potential risksto one’s health concern participants, researchers, and stakeholders (among others). To that end, stringent rules are in place to ensure that participants aren’t subjected to unnecessary risks.

Informed consent—which details the intricacies of the clinical trial and allows volunteers to withdraw from the study at any time—also plays a critical role in participation (and the decision to do so).

Clinical trials must also adhere to a strict code of ethics. This helps guarantee that participants are selected free from prejudice and that the study complies with clinical protocols.

All of that said, the benefits of participating in clinical prevention trials are impressive and, for some, may far outweigh possible drawbacks. Indeed, participants may have the opportunity to:

• Directly assist scientists with gaining deeper insights into their condition or disease

• Contribute to the advancement of treatments and future preventative measures

• Receive in-depth medical care from a broad range of healthcare professionals

• Secure access to a treatment before it becomes available to the public

Participation in a clinical trialhinges on the nature of the study: some studies require healthy participants, while others require a mix of current patients and healthy volunteers.

Additionally, a handful of inclusion criteria figure into eligibility, such as:

• Age

• Gender

• Type of disease

• Stage of disease

All of a study’s eligibility requirements must be met before a volunteer is screened for inclusion. In some cases, participants are chosen if they best represent who the intended treatment will be for.

Importantly, while clinical trials historically assessed white males, they’re becoming increasingly diverse as more and more researchers strive to curb biases and promote health impact.

Clinical trials typically unfold as follows:

• Concept and design: In this stage, clinical researchers outline the concept they want to investigate, whether it’s an experimental treatment for breast cancer patients or a new medical device. This involves determining the methodologies that will be performed, the eligibility criteria of volunteers, and the selection of endpoints. It also includes how the preliminary data will be reviewed and assessed.

• Preparation: Preparing for the trial's commencement involves establishing where the research studies will be conducted, participating in investigator meetings, and receiving regulatory approvals.

• Recruitment: The inclusion criteria established in the first step sets the recruitment stage, including patient screening and informed consent processes.

• Conducting the trial: Clinical trials are generally broken down into four major domains:

  • 1) administer treatment(s)

  • 2) monitor patients

  • 3) gather preliminary data

  • 4) trial management

• Closure: A trial “close-out,” as they’re often called, includes:

  • Finalizing data collection

  • Conducting data analysis

  • Archiving trial material (such as patient samples)

  • Reviewing lessons

  • Notifying regulatory bodies

  • Reporting results and updating the clinical trials registry

Questions to ask before participating in clinical research

Participating in a clinical trial may offer many benefits, but it’s also an extensive, potentially risky commitment. With that in mind, participants are encouraged to gather as much information as possible before consenting.

A few of the most essential questions to ask include:

• What is the primary purpose of the clinical trial?

• How long will it last?

• What are its potential risks?

• What do I stand to gain by participating?

• Does the study pay its volunteers?

• What will I experience?

• How will my safety be assured if I participate?

• Will I receive the results of the trial?

Under informed consent, participants can ask questions before, during, and after the trial.

Clinical trials are categorized as Phase I to IV trials. They are generally described as follows.

Phase I (small number of participants, normally between 6-10 healthy volunteers or very sick patients for whom treatment options are lacking)

Phase I studies are designed to allow scientists and medical doctors to understand how an investigational compound affects human subjects.

The goal is to study what happens to the compound in the body from a safety and tolerability point of view after it is swallowed, injected, or infused. Study participants are monitored for the occurrence and severity of any side effects that they may experience.

Phase II (once the initial safety of the study drug has been confirmed in Phase I trials, Phase II trials are performed on larger groups of patients, generally 20-300, depending on the type of disease)

Phase II studies are designed to begin evaluating the safety and efficacy of an investigational medicine in patients and are often used to determine if different dosages of the treatment have different effects.

The patients are given various doses of the compound and closely monitored to compare the effects and to determine the safest and most effective dosing regimen. Multiple Phase II studies are often conducted to test the compound in various patient populations or indications.

Phase III (carried out on large patient groups, 300–3,000 or more, depending upon the disease being studied)

Phase III studies are designed to confirm the safety and efficacy of an investigational medicine. Large numbers of patients are generally involved in adequately confirming benefits and safety.

As in the earlier phases, these studies may involve one or more ‘treatment arms,’ which allow for the safety and efficacy of the new investigational drug to be compared to other available treatments or tested in combination with other therapies. Information obtained from Phase III studies is used to determine how the compound is best prescribed to patients in the future.

Phase IV (also known as Post-Marketing Surveillance Trials)

Phase IV studies take place after the medicine has received regulatory approval (market authorisation) and are designed to provide broader efficacy and safety data about the new medicine in large numbers of patients or subpopulations of patients and to compare and/or combine it with other available treatments.

These studies are designed to evaluate the drug's long-term effects. Under these circumstances, less common adverse events may be detected.

Clinical trials are an integral part of the drug and diagnostic discovery and development process. Before a new medicine or diagnostic test can be made available, evidence of its safety and effectiveness must be provided by well-designed, well-controlled, and carefully monitored clinical studies in patients who consent to participate.

The principles of nonmaleficence, respect, beneficence, and justice guide ethical clinical research:

• Nonmaleficence is the duty to cause no harm. This principle has its roots in the Hippocratic Oath. The ethical issue at the core of clinical research is whether the research's outcome can reasonably be expected to benefit society without harming the individuals enrolled in the trial.

• Respect for persons is embodied in informed consent, which dictates that information be exhaustive and provided understandably, that the subject’s cooperation be voluntary, and that all information about the subject be confidential.

• Beneficence is demonstrated by a thorough risk/benefit assessment, recognising that benefits can be direct, collateral, and/or altruistic. Similarly, statistical considerations are made regarding physiologic, psychological, and socioeconomic risks. For a clinical trial to be considered ethical, a sufficient body of scientific/medical evidence must exist to justify the exposure of individuals to the risks of the trial. There must be a clear medical need, and the potential benefits to be gained by the research must be weighed against the possible risks to the participating person in the safety and effectiveness of the drug or intervention being studied.

• The principle of justice considers all the processes by which populations are selected for study to ensure that the results benefit the community, avoid exploiting vulnerable populations, and include individuals who may be likely to benefit.

Patients receive state-of-the-art care and free treatment as participants in any of the more than 2,000 Roche-sponsored clinical trials per year. The success of our clinical trials is fundamental to the success of our business. No matter where a Roche clinical trial is conducted or who conducts it, it is essential that we carefully manage all related issues and risks to ensure that:

• the safety, well-being, legal rights, and ethical concerns of those taking part are addressed.

• patients who have benefited from a trial can still access treatment once the trial is complete, even though the tested product may still be awaiting regulatory approval.

• products are made available in all countries where participants live, once the product has been approved.

• patients have the opportunity to join as well as to opt out of clinical trials appropriate for their condition.

• we publish all scientifically and clinically relevant information from clinical trials promptly, to give healthcare professionals a balanced and scientific overview of the performance of our products.

Every person has the basic right to be treated with respect as an independent moral being. The dignity, rights, safety, and well-being of individuals participating in clinical research must be promoted and protected at all times and in any part of the world where clinical trials occur. Since participants in clinical research willingly provide information that cannot be obtained in any other way, they clearly deserve the gratitude and respect of the world community.

Roche is committed to following all international guidelines and local laws and regulations when conducting its clinical research programs. All Roche clinical studies are conducted in full conformance with the principles of the Declaration of Helsinki, a statement of ethical principles developed by the World Medical Association to guide medical research in humans and with the laws and regulations of the country where the research is conducted, whichever affords greater protection to the individual.

An essential aspect of the Declaration of Helsinki is informed consent. The informed consent process should be one of shared information and decision-making in which physicians and participants of the clinical research study openly discuss the research to be done and communicate their goals and values to each other. In this way, the process accommodates both the personal values and the well-being of the research participants and the responsibilities of physicians to make clear the risks and benefits of the research.

The principles outlined in the International Conference on Harmonization (ICH) Tripartite “Guideline for Good Clinical Practice” (January 1997) and national Good Clinical Practice (GCP) guidelines are considered the minimum standard for Roche clinical trials. The GCP guidelines protect patient rights and safety, include standards on how clinical trials should be conducted, and define the roles and responsibilities of clinical trial sponsors, clinical research investigators, and monitors. They also include protection of the human rights of people participating in trials and assurance of the safety and efficacy of newly developed compounds. To ensure compliance with these standards, we require all staff and investigators involved in clinical trials to be trained in ICH and GCP guidelines. Our company-wide compliance assurance process ensures compliance with these requirements in all countries.

Finally, we maintain a public searchable database of clinical trials on https://www.roche-trials.comwhich contains a clinical trial protocol registry that provides information about our Roche-sponsored trials in patients worldwide, plus a database of key results from completed trials, regardless of the outcome.

Roche respects human rights, human dignity, patient safety, and ethical principles. The company is committed to acting ethically and providing the highest standards of care to individuals participating in Roche-sponsored clinical trials.

Roche also commits to protecting the privacy of all individuals participating in Roche trials. This commitment aims to safeguard all personal data protection rights and ensure that no patients suffer any emotional or physical harm because of having participated in a Roche clinical trial.

Consequently, the company welcomes external controls of its clinical trials. The concept of independent oversight requires the review of proposed clinical research projects by qualified individuals independent of the investigators and sponsors. Independent review boards approve and provide oversight to studies involving human beings.

In the US, these are known as Institutional Review Boards (IRBs); in other parts of the world, they are called Independent Ethics Committees (IECs). These boards comprise researchers, ethicists, legal experts, and community members.

Such independent oversight helps ensure the integrity of the clinical research, both from the standpoint of scientific validity and the protection of participating individuals. Thus, a system strives to provide scientific validity while protecting patients’ interests through meaningful informed consent, justice, independent oversight, and a thorough review process.

Each trial must be approved by national and/or regional regulatory authorities as well as local ethics committees or institutional review boards in the countries where a study takes place. These multi-disciplinary panels ensure that proposed trials are acceptable, that participants are fully informed about the related benefits and risks related to the trials and that the healthcare professionals who run the trials (investigational staff) take appropriate actions to protect participants from any harm. . Based on these standards and recommendations, Roche has developed internal policies, systems, and a global position statementto ensure we comply with or exceed all guidelines, regulations, and legal requirements. These are made available to every employee and commit us to a comprehensive range of measures to ensure high ethical conduct.

All Roche employees who work on clinical trials and external contractors working with Roche, including contract research organisations (CROs) that manage trials on our behalf, must strictly adhere to local laws and international guidelines, conduct their research with integrity, and apply the highest standards of medical care and respect for patients at all times. To ensure this compliance, we train, monitor, and audit those involved in our clinical trials. Roche provides Good Clinical Practice (GCP) training to employees working in clinical research, alongside a comprehensive internal education programme to regularly remind our staff of our values and ethical standards.

Furthermore, Roche has established internal processes to facilitate the early discussion and resolution of potential ethical issues that may arise during everyday drug development. This framework incorporates a central point of contact for staff and an escalation process to facilitate the consideration of alternative perspectives when appropriate. Any Roche employee faced with an ethical dilemma can contact the Science and Ethics Advisory Group (SEAG), which operates independently of the clinical teams. The SEAG helps clinical teams find an appropriate answer or escalates the issue to an internal committee of experts. If need be, advice may be requested from an independent external advisory group composed of ethicists and experts from academia and the patient community. This support mechanism allows employees to obtain independent advice, and staff are also obligated to report any suspected issue of noncompliance with regulatory or ethical standards.

During each phase of a clinical trial, Roche’s Global Drug Safety Department evaluates the safety and effectiveness to determine the benefit-risk profile of the medicine. If the risk exceeds the patient benefit, we will modify the study or halt development of that medicine. All members of the Roche community deeply understand and believe in high ethical standards. This translates into each employee's practical application of these standards in his or her daily work responsibilities.

Participants are entitled to a clinical trial that adheres to all legal and ethical standards.

In addition, participants have a right to:

• A clear, transparent Informed Consent process before they agree to join the trial

• Withdraw from the trial at any point in time

The Informed Consent process aims to answer any and all questions relevant to a participant’s decision to agree or decline to join a trial. Only participants who sign an Informed Consent form can enter the trial after having all their questions answered.

With their signature, participants confirm that they have been given all the important facts about a trial, that they understand them, and that they decided to participate in the trial of their own free will.

An Informed Consent document is not a contract. Therefore, a participant may change his or her decision—any participant has the right to withdraw at any point of the trial.

A withdrawal will not affect the participant’s relationship with their doctor nor result in a loss of benefits to which the participant is otherwise entitled. Potential medical risks of a sudden withdrawal from the trial should be detailed in the Informed Consent document.

If a patient agrees to join a trial, some people will need to be informed about participation.

These people are:

• The patient’s primary physician who is responsible for their healthcare on a day-to-day basis

• The doctor and research team looking after the patient in the trial

The fact that a patient is participating in a trial will be written in that patient’s medical notes. Investigators cannot tell anyone else about the patient's participation in a trial unless the patient gives his or her permission.

As with any other medical records, all information collected about the participants will be kept confidential during the trial. When investigators publish the results of a trial, they are not allowed to include any information that would identify people—a patient’s name will not be used in any reports or publications.

The clinical trial protocol will define what is to be done with participant samples and information. Specific sections within this document will detail how long samples and information must be kept before they are destroyed.

If samples and/or information are to be used further, then this will be either:

• Included in the original trial protocol

• Be part of the informed consent a patient signs before they participate in the trial

• Be written up in a specific informed consent form which the patient will also be asked to sign.

Firstly, we will provide, upon request, clinical study reports (CSRs), periodic safety reports, and clinical trial summary reports, either through regulatory bodies such as the EMA or directly.

CSRs contain summaries of data and trial results regarding the medicine's safety and efficacy but will not include any information allowing individual patient identification.

Roche will ask an independent panel of experts to review requests for patient-level anonymised data (rather than CSRs). Access will be based on good scientific merit, which will help patients and doctors use our medicines.

Roche’s trial protocols and results are posted on two public websites: clinicaltrials.govand Roche-trials.com. Finally, we are committed to publishing all of our global studies in medical journals.

This commitment is reflected in the Roche Global Policy on Sharing of Clinical Trials Data,which governs Roche’s Clinical Trial Protocol Registry and Clinical Trial Results Database.This global public database was launched on April 15, 2005, and updated in 2013.

The registry and the results database contain information on all Roche-sponsored clinical trials in patients worldwide for marketed products and interventional clinical studies sponsored by Roche Diagnostics. For further information see Registration of Clinical Trial Protocols and Publication of Clinical Trial Results Policy.

To access Roche’s Clinical Trial Protocol Registry and Clinical Trial Results Database, visit Roche Trials.Information on Roche’s clinical trial protocols can also be accessed via http://clinicaltrials.gov/.

Roche is obliged by the Good Clinical Practice (GCP) international quality standards, regulations, and laws to store the records of its clinical trials for a certain period of time (e.g., 15 or more years). The end of a clinical trial has no impact on the confidentiality of those records; they will still be protected from disclosure to third parties.

We are committed to high-quality and ethical conduct in all clinical trial aspects. For Roche-sponsored trials, Roche commits to providing the investigational medicinal product free for the duration of the study, as required by GCP and in accordance with the country's regulatory requirements.

As part of this commitment and per the Declaration of Helsinki, Roche offers patients who participate in Roche-sponsored clinical trials continued access to the investigational medicinal product they received after trial completion, when appropriate.

Roche will work with qualified Contract Research Organisations (CROs) and other contractors whenever needed. In this context, Roche will apply the Roche Guidelines on Dealing with Suppliers and Service Providers (in force since October 2004).

In particular, the external organisations will be audited regularly to ensure compliance with all Roche policies and procedures. All contractors with which Roche collaborates will be held to the same high ethical standards to which Roche adheres, and Roche employees will carefully supervise their work.

We conduct clinical trials at multiple investigational sites (e.g., hospitals) and in many countries. The geographic diversity of these sites helps ensure the participants represent those who need and will benefit from the new medicine. However, we only perform trials in countries where we plan to market the tested medicine.

We consider several factors when selecting sites for a trial:

• Infrastructure: The country/site(s) should demonstrate experience in clinical trial management activities, which include independent ethics committees and a strong regulatory framework.

• Facilities and training: The selection criteria for Healthcare Professionals (investigators and their staff) should be based on scientific expertise, training (clinical trial management and applicable laws and regulations), qualifications, and site-specific competency and feasibility.

• Patient availability: An adequate patient population should be available and willing to participate in the clinical trials.

Conduct of clinical trials in developing countries presents a unique set of ethical issues. Where Roche undertakes clinical trials in developing countries, the same high standards of ethical conduct and scientific integrity will be adhered to, with the ultimate goal of delivering reliable results after the clinical research.

For further information, see where the results from a Roche-sponsored clinical trial in a low- or middle-income country are used to register the Roche medicinal product in another country. In general, Roche intends to seek marketing authorization in countries where we conduct clinical studies for a particular drug, device, or diagnostics product. A decision to not seek market authorization can be driven by ethical factors such as concerns regarding regional antimicrobial drug stewardship.

The importance of clinical trials cannot be overstated. They play an indispensable role in the progress of medical devices and treatments and the overall improvement of patient care. Participating in one may offer personal advantages, but it can also tremendously benefit society and the future of healthcare as a whole.

Roche is at the vanguard of healthcare innovation. Our mission is to discover highly personalized medicines and diagnostics that are safe, effective, and valuable. Clinical trials are integral to this objective and will allow future patients to lead longer more satisfying lives.

Join Roche on its quest to shape a brighter, healthier, and more equitable tomorrow.