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Phase of clinical research in medicine

Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietary choices, dietary supplements, and medical devices) and known interventions that warrant further study and comparison. Clinical trials generate data on dosage, safety and efficacy. They are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial—their approval does not mean the therapy is 'safe' or effective, only that the trial may be conducted. Depending on product type and development stage, investigators initially enroll volunteers or patients into small pilot studies, and subsequently conduct progressively larger scale comparative studies. Clinical trials can vary in size and cost, and they can involve a single research center or multiple centers, in one country or in multiple countries. Clinical study design aims to ensure the scientific validity and reproducibility of the results. Costs for clinical trials can range into the billions of dollars per approved drug, and the complete trial process to approval may require 7–15 years. The sponsor may be a governmental organization or a pharmaceutical, biotechnology or medical device company. Certain functions necessary to the trial, such as monitoring and lab work, may be managed by an outsourced partner, such as a contract research organization or a central laboratory. Only 10 percent of all drugs started in human clinical trials become approved drugs.

Similarly to drugs, manufacturers of medical devices in the United States are required to conduct clinical trials for premarket approval. Device trials may compare a new device to an established therapy, or may compare similar devices to each other. An example of the former in the field of vascular surgery is the Open versus Endovascular Repair (OVER trial) for the treatment of abdominal aortic aneurysm, which compared the older open aortic repair technique to the newer endovascular aneurysm repair device. An example of the latter are clinical trials on mechanical devices used in the management of adult female urinary incontinence.

Similarly to drugs, medical or surgical procedures may be subjected to clinical trials, such as comparing different surgical approaches in treatment of fibroids for subfertility. However, when clinical trials are unethical or logistically impossible in the surgical setting, case controlled studies will be replaced.

Besides being participants in a clinical trial, members of the public can be actively collaborate with researchers in designing and conducting clinical research. This is known as patient and public involvement (PPI). Public involvement involves a working partnership between patients, caregivers, people with lived experience, and researchers to shape and influence what is researcher and how. PPI can improve the quality of research and make it more relevant and accessible. People with current or past experience of illness can provide a different perspective than professionals and compliment their knowledge. Through their personal knowledge they can identify research topics that are relevant and important to those living with an illness or using a service. They can also help to make the research more grounded in the needs of the specific communities they are part of. Public contributors can also ensure that the research is presented in plain language that is clear to the wider society and the specific groups it is most relevant for.

Although early medical experimentation was performed often, the use of a control group to provide an accurate comparison for the demonstration of the intervention's efficacy was generally lacking. For instance, Lady Mary Wortley Montagu, who campaigned for the introduction of inoculation (then called variolation) to prevent smallpox, arranged for seven prisoners who had been sentenced to death to undergo variolation in exchange for their life. Although they survived and did not contract smallpox, there was no control group to assess whether this result was due to the inoculation or some other factor. Similar experiments performed by Edward Jenner over his smallpox vaccine were equally conceptually flawed. The first proper clinical trial was conducted by the Scottish physician James Lind. The disease scurvy, now known to be caused by a Vitamin C deficiency, would often have terrible effects on the welfare of the crew of long distance ocean voyages. In 1740, the catastrophic result of Anson's circumnavigation attracted much attention in Europe; out of 1900 men, 1400 had died, most of them allegedly from having contracted scurvy. John Woodall, an English military surgeon of the British East India Company, had recommended the consumption of citrus fruit (it has an antiscorbutic effect) from the 17th century, but their use did not become widespread. Lind conducted the first systematic clinical trial in 1747. He included a dietary supplement of an acidic quality in the experiment after two months at sea, when the ship was already afflicted with scurvy. He divided twelve scorbutic sailors into six groups of two. They all received the same diet but, in addition, group one was given a quart of cider daily, group two twenty five drops of elixir of vitriol (sulfuric acid), group three six spoonfuls of vinegar, group four half a pint of seawater, group five received two oranges and one lemon, and the last group a spicy paste plus a drink of barley water. The treatment of group five stopped after six days when they ran out of fruit, but by then one sailor was fit for duty while the other had almost recovered. Apart from that, only group one also showed some effect of its treatment. Each year, May 20 is celebrated as Clinical Trials Day in honor of Lind's research. After 1750 the discipline began to take its modern shape. The English doctor John Haygarth demonstrated the importance of a control group for the correct identification of the placebo effect in his celebrated study of the ineffective remedy called Perkin's tractors. Further work in that direction was carried out by the eminent physician Sir William Gull, 1st Baronet in the 1860s.

Sir Ronald A. Fisher, while working for the Rothamsted experimental station in the field of agriculture, developed his Principles of experimental design in the 1920s as an accurate methodology for the proper design of experiments. Among his major ideas, was the importance of randomization—the random assignment of individuals to different groups for the experiment; replication—to reduce uncertainty, measurements should be repeated and experiments replicated to identify sources of variation; blocking—to arrange experimental units into groups of units that are similar to each other, and thus reducing irrelevant sources of variation; use of factorial experiments—efficient at evaluating the effects and possible interactions of several independent factors. The methodology of clinical trials was further developed by Sir Austin Bradford Hill, who had been involved in the streptomycin trials. From the 1920s, Hill applied statistics to medicine, attending the lectures of renowned mathematician Karl Pearson, among others. He became famous for a landmark study carried out in collaboration with Richard Doll on the correlation between smoking and lung cancer. They carried out a case control study in 1950, which compared lung cancer patients with matched control and also began a sustained long term prospective study into the broader issue of smoking and health, which involved studying the smoking habits and health of more than 30,000 doctors over a period of several years. His certificate for election to the Royal Society called him " the leader in the development in medicine of the precise experimental methods now used nationally and internationally in the evaluation of new therapeutic and prophylactic agents." International clinical trials day is celebrated on 20 May. The acronyms used in the titling of clinical trials is often contrived, and has been the subject of derision.

In many cases, giving a placebo to a person suffering from a disease may be unethical. To address this, it has become a common practice to conduct "active comparator" (also known as "active control") trials. In trials with an active control group, subjects are given either the experimental treatment or a previously approved treatment with known effectiveness.

In such studies multiple experimental treatments are tested in a single trial. Genetic testing enables researchers to group patients according to their genetic profile, deliver drugs based on that profile to that group and compare the results. Multiple companies can participate, each bringing a different drug. The first such approach targets squamous cell cancer, which includes varying genetic disruptions from patient to patient. Amgen, AstraZeneca and Pfizer are involved, the first time they have worked together in a late stage trial. Patients whose genomic profiles do not match any of the trial drugs receive a drug designed to stimulate the immune system to attack cancer.

A clinical trial protocol is a document used to define and manage the trial. It is prepared by a panel of experts. All study investigators are expected to strictly observe the protocol. The protocol describes the scientific rationale, objective(s), design, methodology, statistical considerations and organization of the planned trial. Details of the trial are provided in documents referenced in the protocol, such as an investigator's brochure. The protocol contains a precise study plan to assure safety and health of the trial subjects and to provide an exact template for trial conduct by investigators. This allows data to be combined across all investigators/sites. The protocol also informs the study administrators (often a contract research organization). The format and content of clinical trial protocols sponsored by pharmaceutical, biotechnology or medical device companies in the United States, European Union, or Japan have been standardized to follow Good Clinical Practice guidance issued by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). Regulatory authorities in Canada and Australia also follow ICH guidelines. Journals such as Trials, encourage investigators to publish their protocols.

Clinical trials recruit study subjects to sign a document representing their "informed consent". The document includes details such as its purpose, duration, required procedures, risks, potential benefits, key contacts and institutional requirements. The participant then decides whether to sign the document. The document is not a contract, as the participant can withdraw at any time without penalty. Informed consent is a legal process in which a recruit is instructed about key facts before deciding whether to participate. In general, a larger sample size increases the statistical power, also the cost. The statistical power estimates the ability of a trial to detect a difference of a particular size (or larger) between the treatment and control groups. For example, a trial of a lipid lowering drug versus placebo with 100 patients in each group might have a power of 0.90 to detect a difference between placebo and trial groups receiving dosage of 10 mg/dL or more, but only 0.70 to detect a difference of 6 mg/dL.

Merely giving a treatment can have nonspecific effects. These are controlled for by the inclusion of patients who receive only a placebo. Subjects are assigned randomly without informing them to which group they belonged. Many trials are doubled blinded so that researchers do not know to which group a subject is assigned. Assigning a subject to a placebo group can pose an ethical problem if it violates his or her right to receive the best available treatment. The Declaration of Helsinki provides guidelines on this issue.

Clinical trials designed by a local investigator, and (in the US) federally funded clinical trials, are almost always administered by the researcher who designed the study and applied for the grant. Small scale device studies may be administered by the sponsoring company. Clinical trials of new drugs are usually administered by a contract research organization (CRO) hired by the sponsoring company. The sponsor provides the drug and medical oversight. A CRO is contracted to perform all the administrative work on a clinical trial. For PhasesII–IV the CRO recruits participating researchers, trains them, provides them with supplies, coordinates study administration and data collection, sets up meetings, monitors the sites for compliance with the clinical protocol, and ensures the sponsor receives data from every site. Specialist site management organizations can also be hired to coordinate with the CRO to ensure rapid IRB/IEC approval and faster site initiation and patient recruitment. PhaseI clinical trials of new medicines are often conducted in a specialist clinical trial clinic, with dedicated pharmacologists, where the subjects can be observed by full time staff. These clinics are often run by a CRO which specialises in these studies. At a participating site, one or more research assistants (often nurses) do most of the work in conducting the clinical trial. The research assistant's job can include some or all of the following: providing the local institutional review board (IRB) with the documentation necessary to obtain its permission to conduct the study, assisting with study start up, identifying eligible patients, obtaining consent from them or their families, administering study treatment(s), collecting and statistically analyzing data, maintaining and updating data files during followup, and communicating with the IRB, as well as the sponsor and CRO.

In the context of a clinical trial, quality typically refers to the absence of errors which can impact decision making, both during the conduct of the trial and in use of the trial results.

An Interactional Justice Model may be used to test the effects of willingness to talk with a doctor about clinical trial enrollment. Results found that potential clinical trial candidates were less likely to enroll in clinical trials if the patient is more willing to talk with their doctor. The reasoning behind this discovery may be patients are happy with their current care. Another reason for the negative relationship between perceived fairness and clinical trial enrollment is the lack of independence from the care provider. Results found that there is a positive relationship between a lack of willingness to talk with their doctor and clinical trial enrollment. Lack of willingness to talk about clinical trials with current care providers may be due to patients' independence from the doctor. Patients who are less likely to talk about clinical trials are more willing to use other sources of information to gain a better insight of alternative treatments. Clinical trial enrollment should be motivated to utilize websites and television advertising to inform the public about clinical trial enrollment.

The last decade has seen a proliferation of information technology use in the planning and conduct of clinical trials. Clinical trial management systems are often used by research sponsors or CROs to help plan and manage the operational aspects of a clinical trial, particularly with respect to investigational sites. Advanced analytics for identifying researchers and research sites with expertise in a given area utilize public and private information about ongoing research. Web based electronic data capture (EDC) and clinical data management systems are used in a majority of clinical trials to collect case report data from sites, manage its quality and prepare it for analysis. Interactive voice response systems are used by sites to register the enrollment of patients using a phone and to allocate patients to a particular treatment arm (although phones are being increasingly replaced with web based (IWRS) tools which are sometimes part of the EDC system). While patient reported outcome were often paper based in the past, measurements are increasingly being collected using web portals or hand held ePRO (or ) devices, sometimes wireless. Statistical software is used to analyze the collected data and prepare them for regulatory submission. Access to many of these applications are increasingly aggregated in web based clinical trial portals. In 2011, the FDA approved a PhaseI trial that used telemonitoring, also known as remote patient monitoring, to collect biometric data in patients' homes and transmit it electronically to the trial database. This technology provides many more data points and is far more convenient for patients, because they have fewer visits to trial sites.

A clinical trial produces data that could reveal quantitative differences between two or more interventions; statistical analyses are used to determine whether such differences are true, result from chance, or are the same as no treatment (placebo).

Clinical trials are closely supervised by appropriate regulatory authorities. All studies involving a medical or therapeutic intervention on patients must be approved by a supervising ethics committee before permission is granted to run the trial. The local ethics committee has discretion on how it will supervise noninterventional studies (observational studies or those using already collected data). In the US, this body is called the Institutional Review Board (IRB); in the EU, they are called Ethics committees. Most IRBs are located at the local investigator's hospital or institution, but some sponsors allow the use of a central (independent/for profit) IRB for investigators who work at smaller institutions. To be ethical, researchers must obtain the full and informed consent of participating human subjects. (One of the IRB's main functions is to ensure potential patients are adequately informed about the clinical trial.) If the patient is unable to consent for him/herself, researchers can seek consent from the patient's legally authorized representative. In addition, the clinical trial participants must be made aware that they can withdraw from the clinical trial at any time without any adverse action taken against them. In California, the state has prioritized the individuals who can serve as the legally authorized representative. In some US locations, the local IRB must certify researchers and their staff before they can conduct clinical trials. They must understand the federal patient privacy (HIPAA) law and good clinical practice. The International Conference of Harmonisation Guidelines for Good Clinical Practice is a set of standards used internationally for the conduct of clinical trials. The guidelines aim to ensure the "rights, safety and well being of trial subjects are protected". The notion of informed consent of participating human subjects exists in many countries but its precise definition may still vary. Informed consent is clearly a 'necessary' condition for ethical conduct but does not 'ensure' ethical conduct. In compassionate use trials the latter becomes a particularly difficult problem. The final objective is to serve the community of patients or future patients in a best possible and most responsible way. See also Expanded access. However, it may be hard to turn this objective into a well defined, quantified, objective function. In some cases this can be done, however, for instance, for questions of when to stop sequential treatments (see Odds algorithm), and then quantified methods may play an important role. Additional ethical concerns are present when conducting clinical trials on children (pediatrics), and in emergency or epidemic situations. Ethically balancing the rights of multiple stakeholders may be difficult. For example, when drug trials fail, the sponsors may have a duty to tell current and potential investors immediately, which means both the research staff and the enrolled participants may first hear about the end of a trial through public business news.

In response to specific cases in which unfavorable data from pharmaceutical company sponsored research were not published, the Pharmaceutical Research and Manufacturers of America published new guidelines urging companies to report all findings and limit the financial involvement in drug companies by researchers. The US Congress signed into law a bill which requires PhaseII and PhaseIII clinical trials to be registered by the sponsor on the clinicaltrials. gov website compiled by the National Institutes of Health. Drug researchers not directly employed by pharmaceutical companies often seek grants from manufacturers, and manufacturers often look to academic researchers to conduct studies within networks of universities and their hospitals, e. g., for translational cancer research. Similarly, competition for tenured academic positions, government grants and prestige create conflicts of interest among academic scientists. According to one study, approximately 75% of articles retracted for misconduct related reasons have no declared industry financial support. Seeding trials are particularly controversial. In the United States, all clinical trials submitted to the FDA as part of a drug approval process are independently assessed by clinical experts within the Food and Drug Administration, including inspections of primary data collection at selected clinical trial sites. In 2001, the editors of 12 major journals issued a joint editorial, published in each journal, on the control over clinical trials exerted by sponsors, particularly targeting the use of contracts which allow sponsors to review the studies prior to publication and withhold publication. They strengthened editorial restrictions to counter the effect. The editorial noted that contract research organizations had, by 2000, received 60% of the grants from pharmaceutical companies in the US. Researchers may be restricted from contributing to the trial design, accessing the raw data, and interpreting the results. Despite explicit recommendations  by stakeholders of measures to improve the standards of industry sponsored medical research,   in 2013, Tohen warned of the persistence of a gap in the credibility of conclusions arising from industry funded clinical trials, and called for ensuring strict adherence to ethical standards in industrial collaborations with academia, in order to avoid further erosion of the public's trust. Issues referred for attention in this respect include potential observation bias, duration of the observation time for maintenance studies, the selection of the patient populations, factors that affect placebo response, and funding sources.

Pregnant women and children are typically excluded from clinical trials as vulnerable populations, though the data to support excluding them is not robust. By excluding them from clinical trials, information about the safety and effectiveness of therapies for these populations is often lacking. During the early history of the HIV/AIDS epidemic, a scientist noted that by excluding these groups from potentially life saving treatment, they were being "protected to death". Projects such as Research Ethics for Vaccines, Epidemics, and New Technologies (PREVENT) have advocated for the ethical inclusion of pregnant women in vaccine trials. Inclusion of children in clinical trials has additional moral considerations, as children lack decision making autonomy. Trials in the past had been criticized for using hospitalized children or orphans; these ethical concerns effectively stopped future research. In efforts to maintain effective pediatric care, several European countries and the US have policies to entice or compel pharmaceutical companies to conduct pediatric trials. International guidance recommends ethical pediatric trials by limiting harm, considering varied risks, and taking into account the complexities of pediatric care. an Independent Safety Officer, or for small or low risk studies the principal investigator. For safety reasons, many clinical trials of drugs are designed to exclude women of childbearing age, pregnant women, or women who become pregnant during the study. In some cases, the male partners of these women are also excluded or required to take birth control measures.

Throughout the clinical trial, the sponsor is responsible for accurately informing the local site investigators of the true historical safety record of the drug, device or other medical treatments to be tested, and of any potential interactions of the study treatment(s) with already approved treatments. This allows the local investigators to make an informed judgment on whether to participate in the study or not. The sponsor is also responsible for monitoring the results of the study as they come in from the various sites as the trial proceeds. In larger clinical trials, a sponsor will use the services of a data monitoring committee (DMC, known in the US as a data safety monitoring board). This independent group of clinicians and statisticians meets periodically to review the unblinded data the sponsor has received so far. The DMC has the power to recommend termination of the study based on their review, for example if the study treatment is causing more deaths than the standard treatment, or seems to be causing unexpected and study related serious adverse events. The sponsor is responsible for collecting adverse event reports from all site investigators in the study, and for informing all the investigators of the sponsor's judgment as to whether these adverse events were related or not related to the study treatment. The sponsor and the local site investigators are jointly responsible for writing a site specific informed consent that accurately informs the potential subjects of the true risks and potential benefits of participating in the study, while at the same time presenting the material as briefly as possible and in ordinary language. FDA regulations state that participating in clinical trials is voluntary, with the subject having the right not to participate or to end participation at any time.

The ethical principle of primum non nocere ("first, do no harm") guides the trial, and if an investigator believes the study treatment may be harming subjects in the study, the investigator can stop participating at any time. On the other hand, investigators often have a financial interest in recruiting subjects, and could act unethically to obtain and maintain their participation. The local investigators are responsible for conducting the study according to the study protocol, and supervising the study staff throughout the duration of the study. The local investigator or his/her study staff are also responsible for ensuring the potential subjects in the study understand the risks and potential benefits of participating in the study. In other words, they (or their legally authorized representatives) must give truly informed consent. Local investigators are responsible for reviewing all adverse event reports sent by the sponsor. These adverse event reports contain the opinions of both the investigator (at the site where the adverse event occurred) and the sponsor, regarding the relationship of the adverse event to the study treatments. Local investigators also are responsible for making an independent judgment of these reports, and promptly informing the local IRB of all serious and study treatment related adverse events. When a local investigator is the sponsor, there may not be formal adverse event reports, but study staff at all locations are responsible for informing the coordinating investigator of anything unexpected. The local investigator is responsible for being truthful to the local IRB in all communications relating to the study.

Approval by an Institutional Review Board (IRB), or Independent Ethics Committee (IEC), is necessary before all but the most informal research can begin. In commercial clinical trials, the study protocol is not approved by an IRB before the sponsor recruits sites to conduct the trial. However, the study protocol and procedures have been tailored to fit generic IRB submission requirements. In this case, and where there is no independent sponsor, each local site investigator submits the study protocol, the consent(s), the data collection forms, and supporting documentation to the local IRB. Universities and most hospitals have in house IRBs. Other researchers (such as in walk in clinics) use independent IRBs. The IRB scrutinizes the study both for medical safety and for protection of the patients involved in the study, before it allows the researcher to begin the study. It may require changes in study procedures or in the explanations given to the patient. A required yearly "continuing review" report from the investigator updates the IRB on the progress of the study and any new safety information related to the study.

In the US, the FDA can audit the files of local site investigators after they have finished participating in a study, to see if they were correctly following study procedures. This audit may be random, or for cause (because the investigator is suspected of fraudulent data). Avoiding an audit is an incentive for investigators to follow study procedures. A 'covered clinical study' refers to a trial submitted to the FDA as part of a marketing application (for example, as part of an NDA or 510(k)), about which the FDA may require disclosure of financial interest of the clinical investigator in the outcome of the study. For example, the applicant must disclose whether an investigator owns equity in the sponsor, or owns proprietary interest in the product under investigation. The FDA defines a covered study as " any study of a drug, biological product or device in humans submitted in a marketing application or reclassification petition that the applicant or FDA relies on to establish that the product is effective (including studies that show equivalence to an effective product) or any study in which a single investigator makes a significant contribution to the demonstration of safety." Alternatively, many American pharmaceutical companies have moved some clinical trials overseas. Benefits of conducting trials abroad include lower costs (in some countries) and the ability to run larger trials in shorter timeframes, whereas a potential disadvantage exists in lower quality trial management. Different countries have different regulatory requirements and enforcement abilities. An estimated 40% of all clinical trials now take place in Asia, Eastern Europe, and Central and South America. "There is no compulsory registration system for clinical trials in these countries and many do not follow European directives in their operations", says Jacob Sijtsma of the Netherlands based WEMOS, an advocacy health organisation tracking clinical trials in developing countries. Beginning in the 1980s, harmonization of clinical trial protocols was shown as feasible across countries of the European Union. At the same time, coordination between Europe, Japan and the United States led to a joint regulatory industry initiative on international harmonization named after 1990 as the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)
Currently, most clinical trial programs follow ICH guidelines, aimed at "ensuring that good quality, safe and effective medicines are developed and registered in the most efficient and cost effective manner. These activities are pursued in the interest of the consumer and public health, to prevent unnecessary duplication of clinical trials in humans and to minimize the use of animal testing without compromising the regulatory obligations of safety and effectiveness."

Aggregating safety data across clinical trials during drug development is important because trials are generally designed to focus on determining how well the drug works. The safety data collected and aggregated across multiple trials as the drug is developed allows the sponsor, investigators and regulatory agencies to monitor the aggregate safety profile of experimental medicines as they are developed. The value of assessing aggregate safety data is: a) decisions based on aggregate safety assessment during development of the medicine can be made throughout the medicine's development and b) it sets up the sponsor and regulators well for assessing the medicine's safety after the drug is approved.

Clinical trial costs vary depending on trial phase, type of trial, and disease studied. A study of clinical trials conducted in the United States from 2004 to 2012 found the average cost of PhaseI trials to be between $1.4 million and $6.6 million, depending on the type of disease. Phase II trials ranged from $7 million to $20 million, and PhaseIII trials from $11 million to $53 million.

Investigators are often compensated for their work in clinical trials. These amounts can be small, just covering a partial salary for research assistants and the cost of any supplies (usually the case with national health agency studies), or be substantial and include "overhead" that allows the investigator to pay the research staff during times between clinical trials.

Participants in Phase I drug trials do not gain any direct health benefit from taking part. They are generally paid a fee for their time, with payments regulated and not related to any risk involved. Motivations of healthy volunteers is not limited to financial reward and may include other motivations such as contributing to science and others. In later phase trials, subjects may not be paid to ensure their motivation for participating with potential for a health benefit or contributing to medical knowledge. Small payments may be made for study related expenses such as travel or as compensation for their time in providing follow up information about their health after the trial treatment ends.

Depending on the kind of participants required, sponsors of clinical trials, or contract research organizations working on their behalf, try to find sites with qualified personnel as well as access to patients who could participate in the trial. Working with those sites, they may use various recruitment strategies, including patient databases, newspaper and radio advertisements, flyers, posters in places the patients might go (such as doctor's offices), and personal recruitment of patients by investigators. Volunteers with specific conditions or diseases have additional online resources to help them locate clinical trials. For example, the Fox Trial Finder connects Parkinson's disease trials around the world to volunteers who have a specific set of criteria such as location, age, and symptoms. Other disease specific services exist for volunteers to find trials related to their condition. Volunteers may search directly on ClinicalTrials. gov to locate trials using a registry run by the U. S. National Institutes of Health and National Library of Medicine. There also is software that allows clinicians to find trial options for an individual patient based on data such as genomic data.

The risk information seeking and processing (RISP) model analyzes social implications that affect attitudes and decision making pertaining to clinical trials. People who hold a higher stake or interest in the treatment provided in a clinical trial showed a greater likelihood of seeking information about clinical trials. Cancer patients reported more optimistic attitudes towards clinical trials than the general population. Having a more optimistic outlook on clinical trials also leads to greater likelihood of enrolling. Electronic health records (EHR). Some systems integrate with EHRs to automatically flag patients that may be eligible for trials based on their medical data. These systems may leverage machine learning, artificial intelligence or precision medicine methods to more effectively match patients to trials. These methods are faced with the challenge of overcoming the limitations of EHR records such as omissions and logging errors. Direct to patient services: Resources are specialized to support patients in finding clinical trials through online platforms, hotlines, and personalized support.

Although trials are commonly conducted at major medical centers, some participants are excluded due to the distance and expenses required for travel, leading to hardship, disadvantage, and inequity for participants, especially those in rural and underserved communities. In the 21st century, efforts are made to collect information within a participant's home, a capability improved by telehealth and wearable technologies.