Maninder Kaur, Amritpal Singh


Objective: The main objective of this study is to know clinical trials in nutshell and phase 0 clinical trial are to establish at the very earliest opportunity-before large numbers of patients have been accrued and exposed to potential drug-associated toxicity-whether an agent is modulating its target in a tumor, and consequently whether further clinical development is warranted. We review here the fundamental requirements of clinical studies conducted under an exploratory IND and address some common misconceptions regarding phase 0 trials. Phase 0 clinical trials, developed in response to the United States Food and Drug Administration (FDA)'s recent exploratory Investigational New Drug (IND) guidance, and are intended to expedite the clinical evaluation of new molecular entities. The exploratory IND supports the performance of first-in-human testing of new investigational agents at subtherapeutic doses based on reduced manufacturing and toxicologic requirements, allowing the demonstration of drug-target effects and assessment of pharmacokinetic-pharmacodynamic relationships in humans earlier in clinical development.

Conclusion: From this present review study, we concluded that Phase “0” in clinical trials can work as a useful parameter to measure drug safety at subtherapeutic level and the fundamental requirements of clinical studies conducted under an exploratory IND and address some common misconceptions regarding phase 0 trials.

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Clinicaltrials.gov: A service of the U.S. National Institutes of Health cited from www.cancer.gov/clinicaltrials.

"Clinical Trials". Bill and Melinda Gates Foundation. Retrieved January 2014.

Medline plus: Clinical trials cited from www.nlm.nih.gov/medlineplus/clinicaltrials.html

National Heart, Lung and blood institute: clinical trials cited from www.nhlbi.nih.gov.

cited from www.discoverymedicine.com

Cited from Purpose of clinical trials, www.lungcancer.about.com › Lung Cancer › Lung Cancer Treatment.

cited from www.nhlbi.nih.gov › Clinical Trials

Marc Pocard, Jeans Charles soria, Lydia aldaz carroll and Dominique bellet. Phase 0 Clinical Trials in Oncology: An Exploratory Methodology for Constructing a Study With Patients Undergoing Surgery for Metastatic Disease. 2010.Journal of clinical oncology. 2010, 28(30); 4551-4553.

Comparison of clinical trial phases: Research Coordinator Orientation, University of Pittsburgh, 2002

National Heart, Lung and blood institute: who sponsors clinical trials cited from www.nhlbi.nih.gov › Clinical Trials/sponsors.

"Tax Credit for Testing Expenses for Drugs for Rare Diseases or Conditions". Food and Drug Administration. 17 April 2001. Retrieved 27 March 2007.

Glossary of Clinical Trial Terms, NIH

Helene S (2010). "EU Compassionate Use Programmes (CUPs): Regulatory Framework and Points to Consider before CUP Implementation". Pharm Med 24 (4): 223–229.

Brennan 2013.

"Adaptive Clinical Trials for Overcoming Research Challenges". News-medical.net. Retrieved 2014-01-04.

Wang, Shirley S. (2013-12-30). "Health: Scientists Look to Improve Cost and Time of Drug Trials - WSJ.com". Online.wsj.com. Retrieved 2014-01-04.

Peter W. Huber (12 November 2013). The Cure in the Code: How 20th Century Law Is Undermining 21st Century Medicine.

Pre clinical studies: Latest content: nature.com cited from www.nature.com › Home › Health sciences/preclinical studies.

My medicine: preclinical research: MHRA cited from www.mhra.gov.uk/Safetyinformation/.../Pre-clinicalresearch/.

DeMets, D., Friedman, L., and Furberg, C., (2010). Fundamentals of Clinical Trials. Springer 4th Edition.

"Exploratory IND Studies". Guidance for Industry, Investigators, and Reviewers. Food and Drug Administration. Retrieved 2010-06-15.

The Lancet (2009). "Phase 0 trials: a platform for drug development?". Lancet 374 (9685): 176.

Adil E. Shamoo (2008). "The Myth of Equipoise in Phase 1 Clinical Trials". Medscape J Med 10 (11): 254.

Elizabeth Norfleet, Shayne Cox Gad, "Phase I Clinical Trials", in Shayne Cox Gad, Clinical Trials Handbook, 2009, p. 247


"Guidance for Institutional Review Boards and Clinical Investigators". Food and Drug Administration. 1999-03-16. Retrieved 2007-03-27.

"Periapproval Services (Phase IIIb and IV programs)". Covance Inc. 2005. Retrieved 2007-03-27.

The regulatory authority in the USA is the 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

Arcangelo, Virginia Poole; Andrew M. Peterson (2005).Pharmacotherapeutics for Advanced Practice: A Practical Approach. Lippincott Williams & Wilkins.

Holland, John (2013). "Fixing a broken drug development process". Journal of Commercial Biotechnology 19.

Adams, C. P.; Brantner, V. V. (2006). "Estimating the Cost of New Drug Development: Is It Really $802 Million?". Health Affairs 25 (2): 420–8.

Marjorie Perloff and Vernon ES. Early-Phase Development of Cancer Prevention Agents: Challenges and Opportunities. Cancer Prev Res . 2013.7;179- 181.

Guoliang Li, Gong Chang, Jine wu, Shuting ma, Chaofeng sun. New iPSC for old long QT syndrome modeling: Putting the evidence into perspective. Exp Biol Med. 2014. 239(2); 131-140.

National cancer institute: new approaches to cancer drug development and clinical trials cited from https://ccrod.cancer.gov/confluence/download/.../Phase_0_Trials6.pdf

Jain A. Phase 0 (zero) Clinical trials: A myth or reality?. Indian J cancer. 2010. 47(1);70.

Margaret A. Rogers (June 2009). "What are the phases of intervention research?". American Speech-Language-Hearing Association. Retrieved Jan 8, 2013.

Cited from http://dctd.cancer.gov/About/major_initiatives_NExT.htm

US Department of Health and Human Services, Food and Drug Administration. Guidance for industry, investigators, and reviewers, exploratory IND studies. January 2006.

Phase “0”? in the pipeline: corante, 2007, posted by derek cited from pipeline. corante.com/ archives/2007 /06/ 04/phase_zero.php

Patricia ML. Phase 0 Clinical Trials: An Answer to Drug Development Stagnation. Journal of clinical oncology.2009;27(16); 2586-2588.

Kola I, Landis J. Can the pharmaceutical industry reduce the attrition rates? Nat Rev Drug Discov 2004;3:711-5.

Kummar S, Doroshow JH, Tomaszewski JE, Calvert AH, Lobbezoo M, Giaccone G, et al. Phase 0 (Zero) clinical trials: Recommendations from the task force on methodology for the development of innovative cancer therapies. Eur J Cancer 2009; 45:741-6.

Pharmacists could play vital role in clinical trials education Cited from www.healthcare datasolutions. com/ pharmacists-could-play-vital-role.


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