Editing Clinical trial (section)

==Overview==
===Trials of drugs===

Some clinical trials involve healthy subjects with no [[pre-existing medical conditions]]. Other clinical trials pertain to people with specific health conditions who are willing to try an experimental treatment. Pilot experiments are conducted to gain insights for design of the clinical trial to follow.<ref>{{Cite web |url=https://www.allclinicaltrials.com/blog/what-are-clinical-trials |title=What Are Clinical Trials? |website=AllClinicalTrials.com |publisher=Curify, Inc. |access-date=2025-01-27}}</ref>

There are two goals to testing medical treatments: to learn whether they work well enough, called "efficacy", or "effectiveness"; and to learn whether they are safe enough, called "safety".<ref name=nih-basics/> Neither is an absolute criterion; both safety and efficacy are evaluated relative to how the treatment is intended to be used, what other treatments are available, and the severity of the disease or condition. The benefits must outweigh the risks.<ref>FDA Page last updated 25 April 2014 [https://www.fda.gov/Drugs/ResourcesForYou/Consumers/ucm289601.htm FDA's Drug Review Process: Continued] {{Webarchive|url=https://web.archive.org/web/20190423192717/https://www.fda.gov/Drugs/ResourcesForYou/Consumers/ucm289601.htm |date=23 April 2019 }}</ref><ref>PhRMA. February 2007 [http://www.phrma.org/sites/default/files/pdf/rd_brochure_022307.pdf Drug Discovery and Development] {{Webarchive|url=https://web.archive.org/web/20230410005018/https://www.phrma.org/sites/default/files/pdf/rd_brochure_022307.pdf |date=10 April 2023 }}</ref>{{rp|8}} For example, many drugs to treat cancer have severe side effects that would not be acceptable for an over-the-counter pain medication, yet the cancer drugs have been approved since they are used under a physician's care and are used for a life-threatening condition.<ref>Merck Manual. Last full review/revision October 2013 by Daniel A. Hussar, PhD [http://www.merckmanuals.com/home/drugs/over-the-counter_drugs/overview_of_over-the-counter_drugs.html Overview of Over-the-Counter Drugs] {{Webarchive|url=https://web.archive.org/web/20150204043331/http://www.merckmanuals.com/home/drugs/over-the-counter_drugs/overview_of_over-the-counter_drugs.html |date=4 February 2015 }}</ref>

In the US the elderly constitute 14% of the population, while they consume over one-third of drugs.<ref>Avorn J. (2004). ''Powerful Medicines'', pp. 129–33. Alfred A. Knopf.</ref> People over 55 (or a similar cutoff age) are often excluded from trials because their greater health issues and drug use complicate data interpretation, and because they have different physiological capacity than younger people. Children and people with unrelated medical conditions are also frequently excluded.<ref>{{cite journal | vauthors = Van Spall HG, Toren A, Kiss A, Fowler RA | title = Eligibility criteria of randomized controlled trials published in high-impact general medical journals: a systematic sampling review | journal = JAMA | volume = 297 | issue = 11 | pages = 1233–40 | date = March 2007 | pmid = 17374817 | doi = 10.1001/jama.297.11.1233 }}</ref> Pregnant women are often excluded due to potential risks to the [[fetus]].

The sponsor designs the trial in coordination with a panel of expert clinical investigators, including what alternative or existing treatments to compare to the new drug and what type(s) of patients might benefit. If the sponsor cannot obtain enough test subjects at one location investigators at other locations are recruited to join the study.<ref>{{Cite web |url=https://clinicaltrials.gov/study-basics/learn-about-studies#q8 |title=Who carries out clinical research? |website=ClinicalTrials.gov |publisher=U.S. National Library of Medicine |access-date=2025-01-27}}</ref>

During the trial, investigators recruit subjects with the predetermined characteristics, administer the treatment(s) and collect data on the subjects' health for a defined time period. Data include measurements such as [[vital signs]], concentration of the study drug in the blood or tissues, changes to symptoms, and whether improvement or worsening of the condition targeted by the study drug occurs. The researchers send the data to the trial sponsor, who then analyzes the pooled data using [[statistical hypothesis testing|statistical tests]].{{cn|date=August 2024}}

Examples of clinical trial goals include assessing the safety and relative effectiveness of a medication or device:{{cn|date=August 2024}}
* On a specific kind of patient
* At varying dosages
* For a new indication
* Evaluation for improved efficacy in treating a condition as compared to the standard therapy for that condition
* Evaluation of the study drug or device relative to two or more already approved/common interventions for that condition

While most clinical trials test one alternative to the novel intervention, some expand to three or four and may include a [[placebo]].<ref>{{cite web|date=August 2024|url= https://www.allclinicaltrials.com/blog/what-is-a-single-blind-study|title=What Is A Single Blind Study? Single Blind vs Double Blind Studies}}</ref>

Except for small, single-location trials, the design and objectives are specified in a document called a [[clinical trial protocol]]. The protocol is the trial's "operating manual" and ensures all researchers perform the trial in the same way on similar subjects and that the data is comparable across all subjects.{{cn|date=August 2024}}

As a trial is designed to test [[hypothesis|hypotheses]] and rigorously monitor and assess outcomes, it can be seen as an application of the [[scientific method]], specifically the experimental step.{{cn|date=August 2024}}

The most common clinical trials evaluate new pharmaceutical products, medical devices, [[biologic medical product|biologics]], [[medical diagnosis|diagnostic assays]], [[psychological therapies]], or other interventions.<ref name=fda-types/> Clinical trials may be required before a national [[regulatory authority]]<ref name="reg-auth">The regulatory authority in the US is the [[Food and Drug Administration (United States)|Food and Drug Administration]]; in Canada, [[Health Canada]]; in the [[European Union]], the [[European Medicines Agency]]; and in Japan, the [[Ministry of Health, Labour and Welfare (Japan)|Ministry of Health, Labour and Welfare]]</ref> approves marketing of the innovation.

===Trials of devices===

Similarly to drugs, manufacturers of medical devices in the United States are required to conduct clinical trials for [[premarket approval]].<ref>{{cite web|title=Medical Devices, Premarket Clinical Studies for Investigational Device Exemption|url=https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissions/PremarketApprovalPMA/ucm050419.htm|publisher=US Food and Drug Administration|access-date=2 October 2017|date=17 March 2017|archive-date=1 November 2017|archive-url=https://web.archive.org/web/20171101210345/https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/PremarketSubmissions/PremarketApprovalPMA/ucm050419.htm|url-status=dead}}</ref> 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.<ref name=OVER>{{cite journal | vauthors = Lederle FA, Freischlag JA, Kyriakides TC, Padberg FT, Matsumura JS, Kohler TR, Lin PH, Jean-Claude JM, Cikrit DF, Swanson KM, Peduzzi PN | title = Outcomes following endovascular vs open repair of abdominal aortic aneurysm: a randomized trial | journal = JAMA | volume = 302 | issue = 14 | pages = 1535–42 | date = October 2009 | pmid = 19826022 | doi = 10.1001/jama.2009.1426 | doi-access = free }}</ref> An example of the latter are clinical trials on mechanical devices used in the management of adult female [[urinary incontinence]].<ref>{{cite journal | vauthors = Lipp A, Shaw C, Glavind K | title = Mechanical devices for urinary incontinence in women | journal = The Cochrane Database of Systematic Reviews | issue = 12 | pages = CD001756 | date = December 2014 | volume = 2014 | pmid = 25517397 | doi = 10.1002/14651858.CD001756.pub6 | pmc = 7061494 }}</ref>

===Trials of procedures===

Similarly to drugs, medical or surgical procedures may be subjected to clinical trials,<ref name=PROCEDURE_TRIALS>{{cite journal | vauthors = Farrokhyar F, Karanicolas PJ, Thoma A, Simunovic M, Bhandari M, Devereaux PJ, Anvari M, Adili A, Guyatt G | s2cid = 17084906 | title = Randomized controlled trials of surgical interventions | journal = Annals of Surgery | volume = 251 | issue = 3 | pages = 409–16 | date = March 2010 | pmid = 20142732 | doi = 10.1097/SLA.0b013e3181cf863d }}</ref> such as comparing different surgical approaches in treatment of [[Fibroma|fibroids]] for [[Infertility|subfertility]].<ref>{{Cite journal |last1=Metwally |first1=Mostafa |last2=Raybould |first2=Grace |last3=Cheong |first3=Ying C |last4=Horne |first4=Andrew W |date=2020-01-29 |editor-last=Cochrane Gynaecology and Fertility Group |title=Surgical treatment of fibroids for subfertility |journal=Cochrane Database of Systematic Reviews |language=en |volume=2020 |issue=1 |pages=CD003857 |doi=10.1002/14651858.CD003857.pub4 |pmc=6989141 |pmid=31995657}}</ref> However, when clinical trials are unethical or logistically impossible in the surgical setting, [[case-control study|case-controlled studies]] will be replaced.<ref>{{cite journal | vauthors = Cao AM, Cox MR, Eslick GD | title = Study design in evidence-based surgery: What is the role of case-control studies? | journal = World Journal of Methodology | volume = 6 | issue = 1 | pages = 101–4 | date = March 2016 | pmid = 27019801 | pmc = 4804244 | doi = 10.5662/wjm.v6.i1.101 | doi-access = free }}</ref>

=== Patient and public involvement ===
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.<ref name=":1">{{Cite web |title=Public Information Pack (PIP): How to get involved in NHS, public health and social care research |url=https://www.nihr.ac.uk/documents/public-information-pack-pip-how-to-get-involved-in-nhs-public-health-and-social-care-research/27388 |access-date=January 3, 2024 |website=National Institute for Health and Care Research |language=EN}}</ref> 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.<ref name=":02">{{Cite web |title=Briefing notes for researchers - public involvement in NHS, health and social care research |url=https://www.nihr.ac.uk/documents/briefing-notes-for-researchers-public-involvement-in-nhs-health-and-social-care-research/27371 |access-date=January 3, 2024 |website=National Institute for Health and Care Research |language=EN}}</ref>