the drug is, in comparison with current 'gold standard' treatment. because of their size and comparatively long duration, phase iii trials are the most expensive, time-consuming and difficult trials to design and run, especially in therapies for chronic medical conditions. phase iii trials of chronic conditions or diseases often have a short follow-up period for evaluation, relative to the period of time the intervention might be used in practice. this is sometimes called the "pre-marketing phase" because it actually measures consumer response to the drug. it is common practice that certain phase iii trials will continue while the regulatory submission is pending at the appropriate regulatory agency. this allows patients to continue to receive possibly lifesaving drugs until the drug can be obtained by purchase. other reasons for performing trials at this stage include attempts by the sponsor at "label expansion" (to show the drug works for additional types of patients/diseases beyond the original use for which the drug was approved for marketing), to obtain additional safety data, or to support marketing claims for the drug. studies in this phase are by some companies categorized as "phase iiib studies." while not required in all cases, it is typically expected that there be at least two successful phase iii trials, demonstrating a drug's safety and efficacy, in order to obtain approval from the appropriate regulatory agencies such as fda (us), or the ema (european union). once a drug has proved satisfactory after phase iii trials, the trial results are usually combined into a large document containing a comprehensive description of the methods and results of human and animal studies, manufacturing procedures, formulation details, and shelf life. this collection of information makes up the "regulatory submission" that is provided for review to the appropriate regulatory authorities in different countries. they will review the submission, and if it is acceptable, give the sponsor approval to market the drug. most drugs undergoing phase iii clinical trials can be marketed under fda norms with proper recommendations and guidelines through a new drug application (nda) containing all manufacturing, preclinical, and clinical data. in case of any adverse effects being reported anywhere, the drugs need to be recalled immediately from the market. while most pharmaceutical companies refrain from this practice, it is not abnormal to see many drugs undergoing phase iii clinical trials in the market. adaptive design the design of individual trials may be altered during a trial – usually during phase ii or iii – to accommodate interim results for the benefit of the treatment, adjust statistical analysis, or to reach early termination of an unsuccessful design, a process called an "adaptive design". examples are the 2020 world health organization solidarity trial, european discovery trial, and uk recovery trial of hospitalized people with severe covid-19 infection, each of which applies adaptive designs to rapidly alter trial parameters as results from the experimental therapeutic strategies emerge. adaptive designs within ongoing phase ii–iii clinical trials on candidate therapeutics may shorten trial durations and use fewer subjects, possibly expediting decisions for early termination or success, and coordinating design changes for a specific trial across its international locations. success rate for vaccines, the probability of success ranges from 7% for non-industry-sponsored candidates to 40% for industry-sponsored candidates. a 2019 review of average success rates of clinical trials at different phases and diseases over the years 2005-15 found a success range of 5-14%. separated by diseases studied, cancer drug trials were on average only 3% successful, whereas ophthalmology drugs and vaccines for infectious diseases were 33% successful. trials using disease biomarkers, especially in cancer studies, were more successful than those not using biomarkers. a 2010 review found about 50% of drug candidates either fail during the phase iii trial or are rejected by the national regulatory agency. phase ii/iii cost the amount of money spent on phase ii/iii trials depends on numerous factors, with therapeutic area being studied and types of clinical procedures as key drivers. phase ii studies may cost as much as $20 million, and phase iii as much as $53 million. phase iv a phase iv trial is also known as a postmarketing surveillance trial or drug monitoring trial to assure long-term safety and effectiveness of the drug, vaccine, device or diagnostic test. phase iv trials involve the safety surveillance (pharmacovigilance) and ongoing technical support of a drug after it receives regulatory approval to be sold. phase iv studies may be required by regulatory authorities or may be undertaken by the sponsoring company for competitive (finding a new market for the drug) or other reasons (for example, the drug may not have been tested for interactions with other drugs, or on certain population groups such as pregnant women, who are unlikely to subject themselves to trials). the safety surveillance is designed to detect any rare or long-term adverse effects over a much larger patient population and longer time period than was possible during the phase i-iii clinical trials. harmful effects discovered by phase iv trials may result in a drug being withdrawn from the market or restricted to certain uses; examples include cerivastatin (brand names baycol and lipobay), troglitazone (rezulin) and rofecoxib (vioxx). overall cost the entire process of developing a drug from preclinical research to marketing can take approximately 12 to 18 years and often costs well over $1 billion.