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Good Laboratory Practices (GLPs) came about in the 1970s to improve the confidence of drug safety data for non-clinical laboratory studies. These regulations define the quality system used in non-clinical studies and are meant to ensure the integrity and accuracy of study data as well as the framework for the conduct and reporting of nonclinical laboratory studies. Nonclinical studies are typically performed on animals and focus on the safety testing of drugs that intend to go through human clinical trials.
Animal studies of pharmaceutical products are regulated by GLP and came about as a result of a 1979 FDA inspection of several testing laboratories were conditions were, quite frankly, appalling, and the animals were treated inhumanely. Any laboratory wanting to run animal tests today must maintain clean, adequate facilities, provide proper care for the animals, and conduct valid tests. All non-clinical safety studies of new drugs and new drug applications, drug biologics, veterinary drugs, and some food additives fall under the purview of GLP regulations.
GLPs are regulated by the FDA through the FD&C Act in addition to the Public Health Service Act (PHS Act). Both acts work together to ensure the customer receives a product that is both safe and effective. Human clinical trials are not covered by GLPs as well as preliminary feasibility studies do not have to be conducted under GLP (unless they are performed in animals). Data obtained from non-clinical studies followed under GLPs will be submitted to the FDA to support a product’s overall safety claims. Most FDA centers provide additional directed GLP communication and guidance documents that are unique to the products they oversee. Currently, GLPs are provided by CDER, CBER, CDRH, CVM, and CFSAN.
Bioanalytical specimen handling and analysis are not covered by CLIA. The FDA has provided guidance documents that outline bioanalytical testing, which must include the following validation parameters: accuracy, precision, selectivity, sensitivity, reproducibility, and stability. It’s important to note that these validation parameters should be sought for all GLP method validation practices.
GLP Regulations and Guidelines
In the drug development process, non-clinical studies are performed before an application to perform human studies is submitted. The key elements of a non-clinical study protocol include:
- The facility where the study is conducted
- Standard Operating Procedures (SOPs)
- Personnel involved
- Equipment used
- Drug being studied
- Biological system the drug will be tested
- How you will plan to document the study
- How you will retain the records
GLPs are Regulated by FDA 21 CFR Part 58 and Include
- Toxicology studies in laboratory animals
- Medical device safety testing
- Biochemistry, immunology & microbiology testing
- Eye, dermal and muscle irritation studies
- Pharmacology studies
- Bioanalytical studies
- Color and food additive safety
- Validation of methods for sample analysis
The FDA GLP Regulations
- Subpart A: General Provisions: Type of products regulated (by agency)
- Subpart B: Organization and Personnel: Personnel must have appropriate qualifications
- Subpart C: Facilities: All facilities must be of appropriate size and suitable for study
- Subpart D: Equipment: Equipment is designed appropriately, and function as intended
- Subpart E: Testing Facilities Operation: Test methods, equipment calibration, maintenance, and operation, animal handling SOPs
- Subpart F: Test and Control Articles: Chain of Custody
- Subpart G: Protocol for and Conduct of a non-clinical Laboratory study: Formal study protocol, and study documentation
- Subpart J: Records & Reports: What is needed in the final study report and how the study records
will be stored
Inspection and Enforcement of GLP Laboratories
The FDA may inspect any GLP laboratory to ensure they are following GLP regulations, its physical capabilities in supporting the study, personnel qualifications and training, and equipment. They may perform a routine or surveillance inspection, or they may have a cause to inspect. The primary objectives are outlined in the Bioresearch Monitoring Compliance Program (BIMO) include, which verifies the integrity of data, inspects non-clinical laboratory every two years conducting safety studies, and audits safety studies. More on inspection and enforcement in a later chapter.
It’s important to note that following GLPs does not inherently mean your results will not have errors, and your facilities will not have issues. The value of GLPs is setting up the framework to strengthen your study, and increase oversight, and thereby provide confidence in study results. Keeping excellent and retrievable records provide inspectors and auditors easy access to study data to ensure data is accurate, traceable, and complete.
Section 9(1) of the Pest Control Products Regulations requires that applicants seeking to register pest control products, or registrants wishing to continue such registrations, provide scientific information as will allow the Minister to determine the safety, merit and value of the product. In this respect, the completion of safety related studies in accordance with acceptable Good Laboratory Practice (GLP ) principles is required to support corresponding data quality.
- magnitude of residue
- plant metabolism
- soil metabolism
- rotational crop uptake
- soil dissipation
- effects on mesocosms
- bioaccumulation and
- effects on non-target organisms.
Good Laboratory Practices (GLP) for Pharmaceuticals and other Quality Control Laboratories
Quality Control Laboratory Photo
Good Laboratory Practices (GLP) was first introduced in New Zealand and Denmark in 1972, and later in the US in 1978. It was followed a few years later by the Organization for Economic Co-operation and Development (OECD) Principles of GLP in 1992 & the OECD has since helped promote GLP to many countries.
GLP is not only limited to chemicals but also it applies to medical devices, food additives, food packaging, colour additives and other non-pharmaceutical products or ingredients as well.
What is Good Laboratory Practice (GLP) :
Good Laboratory Practice contains a set of principles that provides a framework within which laboratory studies (Activities) are planned, performed, monitored, recorded, reported and archived. GLP help assure regulatory authorities that the data submitted are a true reflection of the results obtained during the study and can therefore be confidence upon when marking risk/safety assessment.
Why GLP is Important in Pharmaceuticals :
Good Laboratory Practice contains different principles which are designed to ensure and promote consistency, quality, safety, reliability and integrity of chemicals during non-clinical and laboratory testing.
Basic Rules of GLP :
1. Make sure to have the correct written instructions before starting a task.
2. Do not carry out task for which you have not been trained.
3. Keep records of information, results and actions taken. Make clear accurate records of what was done.
4. Check that the instrument/ equipment/material used are clean, calibrated and correct ones as per procedure.
5. Always notify if labels are seen either detached or appear to incorrect or are in wrong place.
6. Never remove a label which has been incorrectly applied and never stick a new label over an old one of the same type. If label is incorrectly affixed strike it off, sign and paste new correct label adjacent to it
7. Clean the glassware drying oven, refrigerator, walk in chamber incubators, water bath of the instruments like dissolution tester, disintegration testers etc, used in the quality control laboratory as per the procedure.
8. Clean the work benches after completion of work or at the end of the day whichever is earlier and keep the respective specification, General test procedure (GTP), Standard test Procedure (SOP’s) etc used back to the designated place.
9. While closing the Quality Control Laboratory, ensure that all water taps, instruments (which are not running), equipments, computers are put ‘OFF’. Put off the lights, AC’s and closes the department.
Premises and Utilities :
1. Maintain the laboratory and its premises clean.
2. Keep work benches of laboratories clean and tidy all the time.
3. Keep the samples, standards, laboratory reagent, apparatus, accessories and records at adequate and suitable storage space.
4. For analytical preparation wherever water is to be used, use purified water for chromatographic analysis like HPLC, GC, etc. use HPLC grade water or water generated by Milli-Q system.
5. The utilities like compressed air, vaccum required for the functioning of laboratory should have identification mark.
6. Maintain temperature and humidity record as per respective procedure wherever applicable.
7. Follow the procedure in case access control system is to be followed where restricted entry is necessary .
8. In case of hazardous and poisonous materials, keep it at adequate storage area/facility with lock and key to avoid misuse. Also keep reserve sample, stability sample, laboratory standards in lock and key.
9. Use eye washer, water shower, first aid kit etc. in case of emergency which may arise during operation & Always identify the location of emergency exit in the laboratory for exit during emergency
2. Personnel suffering from an infectious disease or having open lesion on the exposed surface of the body should not engage in activities that could results in compromising the quality of analysis.
3. All employees shall be instructed to report about their illness or abnormal health condition to their immediate supervisor so that appropriate action can be taken.
4. The job responsibility should be assigned according to competency of the person and it should be timely revised for addition or deletion of responsibilities assigned previously.
5. Smoking, eating, drinking,chilling or keeping plants, food,drinks and personnel medicine should not be permitted in laboratories area, where they might adversely influence the product quality.
6. Personnel should wear clean clothing (company uniform)suitable for activity with which they are involved and this clothing should be changed when appropriate. Personnel should strictly follow entry/exit and gowning procedure.
7. While handling hazardous chemicals and while performing sterility, microbiological analysis, procedure of change of clothing and use of personnel protective equipment’s and safety appliances should be strictly followed.
1. Training should be regularly conducted by qualified individuals and should cover, at a minimum, the particular operation that the employee performs. Training should be given on both the theory and practice of the work being undertaken in a particular area, as well as relevant ‘on-job’ training.
2. Records of training must be maintained. Training should be periodically accessed. All staff, including new staff and existing staff should be given basic training on Good Laboratory Practices during induction and at regular intervals subsequently. This training programme should be periodically updated.
Instruments / Equipments / Accessories :
1. The analytical instrument shall be house in dust free environment and whenever required, conditions of temperature and humidity shall be maintained at periodic checks of temperature and humidity be made and recorded.
2. All instruments / Equipments shall be qualified properly through IQ, OQ and PQ activities after receive in the laboratory.
3. Instruments requiring calibration shall be calibrated at regular intervals and records of such calibration or maintenance be maintained and there shall be written instruction in the form of Standard operating procedures for the operation.
4. Other equipment / accessory such as burette, pipette, volumetric flask, weight boxes, thermometers, etc, shall be thoroughly checked for accuracy of calibration before acceptance for use.
5. Computerized systems should have sufficient controls to prevent unauthorized access or changes to data. Software should not be left opened and unattended to avoid misuse. After use, save the data and close all operating system properly and then switch off the computer system.
6. Water from instrument / equipment (e.g. Dissolution, DT, Sonicators, etc.) should be changed regularly. When Instrument / equipment is not in use for longer period (e.g. breakdown) water should be removed and the instrument /equipment kept dry.
Validation / Verification of Analytical Methods : 1. A written protocol should be established that specifies how Validation /Verification will be conducted. The protocol should be reviewed, approved and authorized by the designated authorities.
2. A Validation / Verification report should be prepared, summarizing the results obtained, and drawing the appropriate conclusions, including recommendation for changes if any, based on the study.
Testing and Reporting :
- Sampling should be done in accordance with approved written procedure
- Sampling staff should trained for sampling activity and should have the knowledge of the nature of the samples to be handled and should refer respective specifications for the same
- Sampled containers should be adequately labelled and should have information for traceability
Testing and Reporting :
- There should be written procedure for testing materials and products at different stage of manufacture, describing the methods and instruments / equipments to be used
- There should be written procedure for testing materials and products at different stage of manufacture, describing the methods and instruments / equipments to be used & Specification should be available for every product / item .
- Testing should be done as per approved specification. The results obtained should be checked for compliance against specification. All calculations should be checked. The records of testing should be maintained.
- Use clean spatulas or butter papers for transferring and weighing samples .
- Attach all relevant analytical raw data obtained from instruments such as Analytical Balances, High Performance Liquid Chromatograph, Gas Chromatograph, UV-Spectrophotometer, IR-Spectrophotometer, Polarimeter, Refractometer, Potentiometer, Bulk Density Apparatus, to the record of analysis / calculation sheet.
- In case of analysis of temperature sensitive material stored at 2-8°C or in freezer (between -25°C to -10°C) .
- During analysis, if any abnormal or unexpected event or out of specification results occurs, address the same using a Incident Report or out of specification report & analysts shall report all Incidents and OOS to the Supervisor or Quality Control Manager as soon as possible.
Stability Studies :
- Stability studies should be carried out to obtain evidence on how the quality of a drug substance or drug product varies with time under the influence of factors such as temperature, humidity and light and enables establishment of recommended storage conditions, retest periods or shelf life for drug substances or drug products.
- A schedule should be designed to monitor the stability of each product .
- Out ofspecification or significant a typical trends should be investigated. Product failures should be promptly reported to technical head, regulatory affairs, R and D, quality assurance and customer, (if applicable), for necessary action. The possible impact on the batches distributed in the market should be considered.
- Asummary of data generated should be written and maintained. This summary should be subjected to periodic review.
Chemicals , Reagents, Glassware and Analytical Standards :
5.1: Good Laboratory Practices (GLPs) - Biology
Good laboratory practice or GLP is a set of principles intended to assure the quality and integrity of non-clinical laboratory studies that are intended to support research or marketing permits for products regulated by government agencies. The term GLP is most commonly associated with the pharmaceutical industry and the required non-clinical animal testing that must be performed prior to approval of new drug products. However, GLP applies to many other non-pharmaceutical agents such as color additives, food additives, food contamination limits, food packaging, and medical devices.
The actual regulations in the United States can be found in 21CFR58 (link) and for the European Union via the Organization for Economic Co-operation and Development (OECD, link). This post is not intended to be a comprehensive review of GLP regulations however, there are some key areas of interest that touch pharmacokineticists. The most important area is the scope of these regulations. Too often the GLP regulations are applied when they should not be used, creating confusion, extra work, and additional costs. Let’s take a look at the scope of GLPs from the FDA documents and the OECD (italics added for emphasis):
This part prescribes good laboratory practices for conducting
non-clinical laboratory studies … (FDA 21CFR58)
These Principles of Good Laboratory Practice should be applied to the non-clinical safety testing … (OECD, No.1)
GLP only applies to non-clinical studies and testing. It does not apply to clinical studies. This is extremely important because clinical studies are governed by Good Clinical Practices (GCP), the Declaration of Helsinki, and other regulations intended to protect human participant safety. Furthermore, much of the GLP structure depends on the roles and responsibilities of the Study Director, a single individual that is responsible for the oversight and execution of all aspects of the non-clinical study. Study Directors do not exist in the clinical study arena, thus GLP principles cannot be applied effectively in the clinical setting.
Beyond the scope, there are two other items I would like to discuss. First, GLP is a quality management system, not a scientific management system. Or, in other words, GLP defines a set of quality standards for study conduct, data collection, and results reporting. GLP does not define scientific standards. If a study follows GLP, then you can be reasonably sure that the reported results were collected as outlined in the study protocol however, you cannot be sure that the study actually addresses the scientific hypothesis. In the world of cooking, GLP would ensure that someone follows the recipe exactly as written however, it does not assure you that the recipe was good or that the resulting item will be tasty!
Second, a key component of the GLP system of quality standards is the idea of a Quality Assurance unit (QA). This QA unit is intended to be an independent group or individual that monitors the entire study conduct, analysis, and reporting. The purpose of QA is to verify that all written procedures are followed throughout the study. As an example, perhaps there is an SOP that says that a senior pharmacokineticist must review the results prior to finalization. The QA auditor will verify that this review occurred. Verification could be done by reviewing a signed document, reviewing an electronic signature, or even speaking directly with the reviewer. The QA auditor will ensure that the senior pharmacokineticist has adequate training (as defined by SOPs in the organization) to perform his or her duties. This quality audit permits confidence that procedures were followed. But again, this audit does not ensure that the procedures are of high quality, or that no errors are made in the analysis.
Here are a few examples of how I think GLPs are misinterpreted:
- Using GLP to perform bioanalysis for human clinical trials. As noted in the scope for both GLP and OECD GLP, the principles of GLP only apply to non-clinical studies. Therefore, following GLP, particularly with respect to QA reviews is an unnecessary cost. It is more important to follow analytical validation plans.
- Performing GLP as a single person. GLP work requires at minimum 2 or 3 individuals. These are the person performing the work (analyst), a person reviewing the work (management), and a quality assurance reviewer (QA). If SOPs are written well, the analyst and the management can be the same individual however, QA must always be an independent person.
- Results of GLP studies are “right.” A statement that a study was conducted in conformance with GLP simply means that quality systems were followed, and that the results of the study accurately report the conduct of the study. It does not indicate that the conclusions drawn are accurate, scientifically robust, or even useful!
I hope you take some time to learn more about GLP and apply it correctly in your future work.
The FDA has mandated that sponsors use the CDISC SEND format for electronic submissions. To learn how NCA data needs to be prepared, transformed, and formatted to be SEND-ready and how Phoenix tools can save time, reduce errors, and increase compliance, please watch this webinar.
Purpose and principles of GLP
GLP is a quality system which applies to preclinical safety studies on chemicals, pharmaceuticals, veterinary medicines, pesticides and biocides.
Manufacturers are obliged to conduct (or commission) such studies in order to demonstrate the safety of a product to the relevant receiving/regulatory authority, such as the Medicines Evaluation Board in the Netherlands. Only then will a new product or substance be granted a marketing authorization allowing it to be distributed through the regular channels.
Safety studies serve to establish that the product poses no risk to human health, animal health and/or the environment.
Purpose of GLP
The purpose of the Principles of GLP is:
- to promote the quality of test data
- to avoid duplication of research
- to improve the protection of human health and environment
- to facilitate international acceptance of test data
- to prevent the creation of technical trade barriers.
Actions after an inspection
After the inspection closing meeting, you will receive an inspection report within 25 working days confirming any deficiencies found.
You must respond to the inspector by email to confirm the proposed corrective actions and dates for when these actions will be completed.
The inspector will review your response. Once the inspector is satisfied with the actions proposed a statement of GLP compliance will be issued.
At this point a risk assessment will be carried out and the date and scope of your next compliance monitoring inspection will be decided.
Risk-based compliance programme
The authors declare that they have no competing interests.
Marinella Marzano conceived and designed the experiments, performed the experiments, analyzed the data, wrote the paper, prepared figures and/or tables, reviewed drafts of the paper.
Caterina Manzari conceived and designed the experiments, performed the experiments, analyzed the data, wrote the paper, prepared figures and/or tables, reviewed drafts of the paper.
Daniela Filannino contributed reagents/materials/analysis tools.
Rosella Pizzi contributed reagents/materials/analysis tools.
Anna Maria D'Erchia contributed reagents/materials/analysis tools.
Claudia Lionetti performed the experiments, prepared figures and/or tables.
Ernesto Picardi contributed reagents/materials/analysis tools.
Giuseppe Sgaramella performed the experiments.
Graziano Pesole conceived and designed the experiments, contributed reagents/materials/analysis tools, wrote the paper, reviewed drafts of the paper.
Antonella Lanati conceived and designed the experiments, performed the experiments, analyzed the data, wrote the paper, prepared figures and/or tables, reviewed drafts of the paper.
Francesca De Leo conceived and designed the experiments, performed the experiments, analyzed the data, wrote the paper, prepared figures and/or tables, reviewed drafts of the paper.
The following information was supplied regarding data availability:
The research in this article did not generate, collect or analyse any raw data or code.
The project has been supported by The Molecular Biodiversity Laboratoy (MoBiLab) of Lifewatch ITA and by the Project "BIOforIU - Infrastruttura multidisciplinare per lo studio e la valorizzazione della Biodiversità marina e terrestre nella prospettiva della “Innovation Union”. PON3_00025. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
This work was supported in part by an appointment to A.S.G. to the Research Participation Program at the Centers for Disease Control and Prevention, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the CDC. H.L.R. was supported in part by National Institutes of Health grants U01HG006500 and U41HG006834. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the CDC, the Agency for Toxic Substances and Disease Registry or the FDA. Certain commercial equipment, instruments or materials are identified in this document. Such identification does not imply recommendation or endorsement by the CDC, the Agency for Toxic Substances and Disease Registry, the FDA or NIST, nor does it imply that the products identified are necessarily the best available for the purpose.
GLP, Part 1, “Good Laboratory Practices:” Obsolete Federal Science, Jeopardizing Public Health.
Federal regulatory science is flawed in many aspects, but one of the primary reasons lies in the outdated and rudimentary rules embodied in “Good Laboratory Practices” (GLP).
GLP was created in 1978 as a reaction to fraudulent science, but requires only a set of rock-bottom, rudimentary rules for basic lab practices. Any college student who earns a “C” in a sophomore-level science lab must master an equivalent set of rules.
Despite its intent, GLP has done little to stop shoddy science because studies for regulatory science are based on outdated science and laboratory methods and are conducted mostly in secret by corporations and the private laboratories they hire.
GLP’s outdated and frequently inappropriate rules are often and easily “gamed” by private labs who have learned how to create regulatory approval by the savvy application of scientific half-truths, fraud, procedural loopholes, obsolete science, and other significant scientific and ethical lapses.
According to this article about GLP in Environmental Health Perspectives (EHP), the federal government’s obsession with GLP has resulted in flawed regulatory decisions that can adversely affect public health. EHP is a scientific journal published by the National Institutes of Health.
GLP’s Origin In Scientific Fraud
According to the EHP article, the need for better standards or corporate science was illustrated when two men from a private science company were sentenced to prison in 1983 for deliberately skewing results of tests to make it easier for chemical company clients to gain regulatory approval.
“What began as serious concerns about poor quality research expanded into a criminal investigation of Industrial Bio-Test (IBT), one of the largest private laboratories at the time and a subsidiary of Nalco Chemical Company,” said the EHP article.
“In response to the federal investigation, the U.S. Environmental Protection Agency (EPA) demanded that 235 chemical companies reexamine the >4,000 tests conducted by the laboratory.
“In 1983, three men from IBT were found guilty of deliberating doctoring data and were sentenced to prison. The fraudulent practices of IBT brought into question 15% of the pesticides approved for use in the United States. That same year, the U.S. EPA issued similar GLP rules for regulatory testing.”
This article shows how fraud continues to plague corporate science: Covertly Stretching “Peer Review” Until It Breaks
Sophomore-Level Science Standards
The EHP article notes that “GLP outlines basic guidelines for conducting scientific research, including the care and feeding of laboratory animals, standards for facility maintenance, calibration and care of equipment, personnel requirements, inspections, study protocols, and collection and storage of raw data.”
Proper adherence to those fundamental basics is one of the lowest bars a college sophomore biology or chemistry student must master on the way to a “C.”
NIH Standards Stricter, Yet Rejected By Regulators
“[T]he procedures of GLP are actually surpassed by the procedures required for NIH-funded science published in peer-reviewed journals.
“NIH-funded studies pass through three phases of peer review that are far more challenging than GLP requirements.
“First, the principal scientists must have demonstrated competence to conduct the research, and experimental methods, assays, and laboratory environment must involve use of state-of-the-art techniques to be competitive for NIH funding.
“Second, results are published in peer-reviewed journals, with detailed evaluations by independent experts examining all aspects of the study.
“And third, the findings are challenged by independent efforts to replicate….”
FDA In Forefront Of GLP Support
The EHP article pointed out that the Food and Drug Administration ruled that the chemical BPA (Bisphenol A) was safe only after rejecting more than 700 peer-reviewed, published studies done to NIH standards because they did not adhere to the looser GLP rules.
Instead, the FDA made its safety determination on two chemical company-funded studies because they used GLP.
The EHP article noted that independent researchers later found those studies flawed and their results unreliable.
The federal government’s substandard science and its misguided preference for GLP over university studies was dissected in detail in this article from the Boston University School of Law: Equal Treatment for Regulatory Science
GLP: No Guarantee Against Incompetence Or Carelessness
The NIH standards and associated scrutiny of researchers and the design and conduct of their experiments provide solid safeguards for reliable, reproducible and honest science.
GLP, on the other hand, offers many opportunities for misconduct, incompetence and carelessness.
This 2014 article details the pitiful state of some GLP experiments and the appalling incompetence of those who practice it: Bad FDA Science Makes For Bad Public Health That study on Bisphenol A makes so many bone-headed and obvious experimental errors that it would merit an “F” in high-school biology.
More incompetence of this nature remains un-exposed because of time and career concerns. It took literally weeks to create the scientific paper underpinning that FDA piece: Low-Dose BPA Paper In Toxicological Sciences is Contaminated By Massive Errors & Should Be Retracted.
Few NIH-level researchers have the time to devote to dissecting badly done GLP studies.
But there is a bigger issue that keeps even the most ardent opponents of GLP incompetence from speaking up: career issues. The FDA and other federal agencies have money and facilities that are rarely made available to dissenters.
While corporate science and private labs have virtually limitless funds to conduct secret, substandard GLP studies, those who do the best and most reliable science remain under-funded and vulnerable to being left out in the cold if they point out the regulatory emperor’s clothes.
More details of a few of the FDA’s other failures can be found here: Just Because The FDA Says Something’s Safe Doesn’t Mean It Is.
Reliability and Validity
The EHP article emphasized that:
“Of central importance is that the results of a study must be reproduced under a similar methodology to be considered to be reliable.
“Validity” refers to whether the research measures what it was intended to measure, and valid findings are considered to be true.
“In other words, reliability is determined by whether the results are replicable, whereas validity is assessed by whether the methods used result in finding the truth as a result of the investigator actually measuring what the study intended to measure.
“Unfortunately, although GLP creates the semblance of reliable and valid science, it actually offers no such guarantee.
“GLP specifies nothing about the quality of the research design, the skills of the technicians, the sensitivity of the assays, or whether the methods employed are current or out-of-date. (All of the above are central issues in the review of a grant proposal by an NIH panel.)
“GLP simply indicates that the laboratory technicians/scientists performing experiments follow highly detailed U.S. EPA requirements [or in the EU, Organization for Economic Co-operation and Development (OECD) requirements] for record keeping, including details of the conduct of the experiment and archiving relevant biological and chemical materials.”
FDA Ignores Highest Standard Of Research: Reproducibility
The gold standard in scientific research is reproducibility: Can the experimental results be replicated by independent third parties? And not just reproduced once, but many times.
However, reproducibility requires complete transparency, ethical scientists and competent science. There must also be publication of the results along with all the protocols and other details that allow another scientist to duplicate the experiment and the results. This extensive series of articles demonstrates why federal and corporate science fails at every step and cannot afford the scrutiny that transparency sould bring.
According to the EHP article:
“Typically, within a laboratory, interesting findings are also followed by subsequent publications extending the prior findings…. In particular, independent replication by competent, respected scientists is the main criterion of acceptance of the findings as having been demonstrated to be reliable and having been validated by virtue of coming to the same conclusion using a variety of sophisticated techniques in multiple publications.
“[T]he U.S. FDA, in its assessment of the now  approximately 1,000 articles on BPA, is that it appears to have made no attempt to connect the dots between replicated studies instead, the U.S. FDA appears to have assessed each study without regard to whether it had been confirmed by other studies.
“Thus, collectively, many phases used to verify the reliability and validity of NIH-funded published research have been completely ignored by the U.S. FDA, whereas industry-funded GLP research is rarely, if ever, subject to these central requirements and yet is accepted by regulatory agencies as reliable and valid.”
Sadly, the vast majority of GLP studies used for regulatory approval are kept secret and cannot be reproduced or validated.
These studies are created by private labs and corporations who are allowed to unilaterally declare the studies as “confidential business information.”
American Chemical Council Supports GLP
Unsurprisingly, the American Chemical Council (ACC) — the industry trade and lobbying association — was the only defender of GLP against the charges leveled in the EHP article: Good Laboratory Practices and Safety Assessments.
Significantly, the ACC has a serious load of its own fraud issues which vastly undermine the article’s credibility.
In this piece, a former ACC consultant shows how the ACC lied about its lobbying role on flame retardants.
And this article A Lack Of Ethics: Covertly Stretching “Peer Review” Until It Breaks, uses exhibits in a federal court case to demonstrate how the ACC admitted to a continuing practice of laundering industry money to recruit shills willing write derogatory comments regarding published studies it disagreed with.
The authors of the original EHP piece — on which this article is based — responded with documented details — Good Laboratory Practices: Comments — that gutted the ACC’s contentions.
Glossary of Commonly Used Terms in Research Ethics
Note: This glossary is intended for educational or research purposes only and is not intended to provide legal advice or replace or contravene existing laws or institutional policies. Send comments to: [email protected] . Many of the definitions are based on Shamoo AE and Resnik DB, Responsible Conduct of Research, 3rd ed. (New York: Oxford University Press, 2015).
Accountability: taking personal responsibility for one&rsquos conduct.
Accreditation: a process in which an accrediting body determines whether an institution or organization meets certain standards developed by the body. For example, the Association for the Assessment and Accreditation of Laboratory Animal Care (AAALAC) accredits animal research programs, and the Association for the Accreditation of Human Research Protection Programs (AAHRPP) accredits human subjects research programs.
Adverse event (AE): a medically undesirable event occurring in a research subject, such as an abnormal sign, symptom, worsening of a disease, injury, etc. A serious adverse event (SAE) results in death, hospitalization (or increased hospital stay), persistent disability, birth defect, or any other outcome that seriously jeopardizes the subject&rsquos health. AEs which are also unanticipated problems should be reported promptly to institutional review boards and other appropriate officials.
Amendment: a change to a human subjects research protocol approved by an institutional review board or the board&rsquos chair (if the change is minor).
Animal rights: the view that (non-human) animals have moral or legal rights. Proponents of animal rights tend to regard animal experimentation as unethical because animals cannot consent to research.
Animal welfare: 1. The health and well-being of animals. 2. The ethical obligation to protect and promote animal welfare in research. Factors affecting animal welfare include: food, water, housing, climate, mental stimulation, and freedom from pain, suffering, disease, and disability. See also Three Rs.
Asilomar Conference: a meeting of scientists, held in Asilomar, CA in 1975, who were involved in development recombinant DNA techniques concerning the oversight of responsible use of this technology. The scientists recommended the development of safety protocols as a means of protecting laboratory workers and the public from harm.
Assent: a subject&rsquos affirmative agreement to participate in research. Assent may take place when the subject does not have the capacity to provide informed consent (e.g. the subject is a child or mentally disabled) but has the capacity to meaningfully assent. See Informed Consent.
Audit: a formal review of research records, policies, activities, personnel, or facilities to ensure compliance with ethical or legal standards or institutional policies. Audits may be conducted regularly, at random, or for-cause (i.e. in response to a problem).
Author: a person who makes a significant contribution to a creative work. Many journal guidelines define an author as someone who makes a significant contribution to 1) research conception and design, 2) data acquisition, or 3) data analysis or interpretation and who drafts or critically reads the paper and approves the final manuscript.
Authorship, ghost: failing to list someone as an author on a work even though they have made a significant contribution to it.
Authorship, honorary: receiving authorship credit when one has not made a significant contribution to the work.
Autonomy: 1. the capacity for self-governance, i.e. the ability to make reasonable decisions. 2. A moral principle barring interference with autonomous decision-making. See Decision-making capacity.
Bad apples theory: the idea that most research misconduct is committed by individuals who are morally corrupt or psychologically ill. This idea can be contrasted with the view that social, financial, institutional, and cultural factors play a major role in causing research misconduct. See Culture of integrity.
Belmont Report: A report issued by the U.S. National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research in 1979, which has had a significant influence over human subjects research ethics, regulation, and policy. The report provided a conceptual foundation for the Common Rule and articulated three principles of ethics: respect for persons, beneficence, and justice.
Beneficence: the ethical obligation to do good and avoid causing harm. See also Belmont Report.
Benefit: a desirable outcome or state of affairs, such as medical treatment, clinically useful information, or self-esteem. In the oversight of human subjects research, money is usually not treated as a benefit.
Bias: the tendency for research results to reflect the scientist&rsquos (or sponsor's) subjective opinions, unproven assumptions, political views, or personal or financial interests, rather than the truth or facts. See also Conflict of Interest.
Biobank: a repository for storing biological samples or data to be used in research. Biobanks usually require investigators or institutions to agree to certain conditions as a condition for sharing samples or data with them.
Bioethics: the study of ethical, social, or legal issues arising in biomedicine and biomedical research.
Censorship: taking steps to prevent or deter the public communication of information or ideas. In science, censorship may involve prohibiting the publication of research or allowing publication only in redacted form (with some information removed).
Citation amnesia: failing to cite important work in the field in a paper, book, or presentation.
Classified research: research that the government keeps secret to protect national security. Access to classified research is granted to individuals with the appropriate security clearance on a need-to-know basis.
Clinical investigator: a researcher involved in conducting a clinical trial.
Clinical trial: an experiment designed to test the safety or efficacy of a type of therapy (such as a drug).
Clinical trial, active controlled: a clinical trial in which the control group receives a treatment known to be effective. The goal of the trial is to compare different treatments.
Clinical trial, placebo controlled: a clinical trial in which the control group receives a placebo. The goal of the trial is to compare a treatment to a placebo.
Clinical trial, phases: sequential stages of clinical testing, required by regulatory agencies, used in the development of medical treatments. Pre-clinical testing involves experiments on animals or cells to estimate safety and potential efficacy. Phase I trials are small studies (50-100 subjects) conducted in human beings for the first time to assess safety, pharmacology, or dosing. Phase I studies are usually conducted on healthy volunteers though some are conducted on patients with terminal diseases, such as cancer patients. Phase II trials are larger studies (500 or more subjects) conducted on patients with a disease to assess safety and efficacy and establish a therapeutic dose. Phase III trials are large studies (up to several thousand subjects) conducted on patients to obtain more information on safety and efficacy. Phase IV (or post-marketing) studies are conducted after a treatment has been approved for marketing to gather more information on safety and efficacy and to expand the range of the population being treated.
Clinical trial, registration: providing information about a clinical trial in a public registry. Most journals and funding agencies require that clinical trials be registered. Registration information includes the name of the trial, the sponsor, study design and methods, population, inclusion/exclusion criteria, and outcome measures.
Clinical utility: the clinical usefulness of information, e.g. for making decisions concerning diagnosis, prevention, or treatment.
Coercion: using force, threats, or intimidation to make a person comply with a demand.
Collaboration agreement: an agreement between two or more collaborating research groups concerning the conduct of research. The agreement may address the roles and responsibilities of the scientists, access to data, authorship, and intellectual property.
Commercialization: the process of developing and marketing commercial products (e.g. drugs, medical devices, or other technologies) from research. See also Copyrights, Intellectual Property, Patents.
Common law: a body of law based on judicial decisions and rulings.
Common Rule: The U.S. Department of Health and Human Services regulations (45 CFR 46) for protecting human subjects, which has been adopted by 17 federal agencies. The Common Rule includes subparts with additional protections for children, neonates, pregnant women and fetuses, and prisoners.
Community review: a process for involving a community in the review of research conducted on members of the community. Some research studies include community advisory boards as a way of involving the community.
Competence: the legal right to make decisions for one&rsquos self. Adults are considered to be legally competent until they are adjudicated incompetent by a court. See Decision-making capacity.
Compliance: in research, complying with laws, institutional policies and ethical guidelines related to research.
Conduct: Action or behavior. For example, conducting research involves performing actions related to research, such as designing experiments, collecting data, analyzing data, and so on.
Confidentiality: the obligation to keep some types of information confidential or secret. In science, confidential information typically includes: private data pertaining to human subjects, papers or research proposals submitted for peer review, personnel records, proceedings from misconduct inquiries or investigations, and proprietary data. See also Privacy.
Conflict of interest (COI): a situation in which a person has a financial, personal, political or other interest which is likely to bias his or her judgment or decision-making concerning the performance of his or her ethical or legal obligations or duties.
Conflict of interest, apparent or perceived: a situation in which a person has a financial, personal, political or other interest that is not likely to bias his or her judgment or decision-making concerning the performance of his or her ethical or legal obligation or duties but which may appear to an outside observer to bias his or her judgement or decision-making.
Conflict of interest, institutional: a situation in which an institution (such as a university) has financial, political, or other interests which are likely to bias institutional decision-making concerning the performance of institutional ethical or legal duties.
Conflict of interest, management: strategies for minimizing the adverse impacts of a conflict of interest, such as disclosure, oversight, or recusal/prohibition.
Consent: See Informed consent.
Consequentialism: an approach to ethics, such as utilitarianism, which emphasizes maximizing good over bad consequences resulting from actions or policies.
Continuing review: in human subjects research, subsequent review of a study after it has been approved by an IRB. Continuing review usually happens on an annual basis.
Copyright: a right, granted by a government, which prohibits unauthorized copying, performance, or alteration of creative works. Copyright laws include a fair use exemption which allows limited, unauthorized uses for non-commercial purposes.
Correction (or errata): fixing a minor problem with a published paper. A minor problem is one that does not impact the reliability or integrity of the data or results. Journals publish correction notices and identify corrected papers in electronic databases to alert the scientific community to problems with the paper. See also Retraction.
Culture of integrity: the idea that the institutional culture plays a key role in preventing research misconduct and promoting research integrity. Strategies to promote a culture of integrity include education and mentoring in the responsible conduct of research research policy development institutional support for research ethics oversight, consultation, and curriculum development and ethical leadership.
Emergency research: in human subjects research, research that is conducted when a subject who cannot provide informed consent faces a life-threatening illness that requires immediate treatment and has no available legally authorized representative to provide consent. The Food and Drug Administration has developed special rules for emergency research involving products that it regulates.
Error: an unintended adverse outcome a mistake.
Ethical dilemma: A situation in which two or more potential actions appear to be equally justifiable from an ethical point of view, i.e. one must choose between the lesser of two evils or the greater of two goods.
Ethical reasoning: Making a decision in response to a moral dilemma based a careful and thorough assessment of the different options in light of the facts and circumstances and ethical considerations.
Ethical relativism: The view that ethical standards are relative to a particular culture, society, historical period, etc. When in Rome, do as the Romans do. See Ethical universalism.
Ethical theory: A set of statements that attempts to unify, systematize, and explain our moral experience, i.e. our intuitions or judgments about right/wrong, good/bad, etc. See Kantianism, Utilitarianism, Virtue ethics.
Ethical universalism: The view that the same standards of ethics apply to all people at all times.
Ethics (or morals): 1. Standards of conduct (or behavior) that distinguish between right/wrong, good/bad, etc. 2. The study of standards of conduct.
Ethics, applied: The study of ethics in specific situations, professions, or institutions, e.g. medical ethics, research ethics, etc.
Ethics, meta-: The study of the meaning, truth, and justification of ethical statements.
Ethics, normative vs. descriptive: Normative ethics studies the standards of conduct and methods of reasoning that people ought to follow. Descriptive ethics studies the standards of conduct and reasoning processes that people in fact follow. Normative ethics seeks to prescribe and evaluate conduct, whereas descriptive ethics seeks to describe and explain conduct. Disciplines such as philosophy and religious studies take a normative approach to ethics, whereas sociology, anthropology, psychology, neuroscience, and evolutionary biology take a descriptive approach.
Exempt research: human subjects research which is exempted from review by an institutional review board. Some types of exempt research include research on existing human samples or data in which the researcher cannot readily identify individuals and anonymous surveys of individuals.
Exculpatory language: language in an informed consent form, contract, or other document intended to excuse a party from legal liability.
Expedited review: in human subjects research, review of a study by the chair of an institutional review board (or designee) instead of by the full board. Expedited review may be conducted on new studies that pose minimal risks to subjects, for continuing review in which a study is no longer recruiting subjects, or on amendments to approved studies that make only minor changes.
Exploitation: taking unfair advantage of someone else.
Expression of concern: a journal may publish an expression of concern when a paper has come under suspicion for wrongdoing or is being investigated for possible research misconduct.
Fabrication: making up data or results.
Falsification: changing, omitting, or manipulating data or results deceptively or deceptive manipulation of research materials or experiments.
Food and Drug Administration (FDA): a federal agency in charge of approving the marketing of drugs, biologics, medical devices, cosmetics, and food additives. The FDA has adopted human subjects research regulations which are similar to the Common Rule however, the FDA rules do not allow exceptions from informed consent requirements unless a study qualifies as Emergency research.
Fraud: knowingly misrepresenting the truth or concealing a material (or relevant) fact to induce someone to make a decision to his or her detriment. Some forms of research misconduct may also qualify as fraud. A person who commits fraud may face civil or criminal legal liability.
Freedom of Information Act (FOIA): a law enacted in the U.S. and other countries which allows the public to obtain access to government documents, including documents related to government-funded scientific research, such as data, protocols, and emails. Several types of documents are exempt from FOIA requests, including classified research and confidential information pertaining to human subjects research.
Good clinical practices (GCPs): rules and procedures for conducting clinical trials safely and rigorously.
Good laboratory practices (GLPs): rules and procedures for designing and performing experiments or tests and recording and analyzing data rigorously. Some types of research are required by law to adhere to GLPs.
Good manufacturing practices (GMPs): rules and procedures for manufacturing a product (such as a drug) according to standards of quality and consistency.
Good record-keeping practices (GRKPs): rules and procedures for keeping research records. Records should be thorough, accurate, complete, organized, signed and dated, and backed-up.
Guideline: a non-binding recommendation for conduct.
Harassment: unwelcome (e.g. aggressive, offensive, intimidating, inappropriate) conduct in the workplace based on one's race, gender, sexual identity, national origin, age, religion, or disability status. Harassment can be physical or non-physical and may be unwelcome because it creates a hostile work environment or because submitting to or rejecting the conduct is likely to result in actions favorable or dis-favorable to the employee (i.e. "quod pro quo" harassment).
Harassment, sexual: harassment involving unwelcome sexual advances or remarks or requests for sexual favors.
Helsinki Declaration: ethical guidelines for conducting medical research involving human subjects research adopted by the World Medical Association.
Honesty: the ethical obligation to tell the truth and avoid deceiving others. In science, some types of dishonesty include data fabrication or falsification, and plagiarism.
Human subjects research: research involving the collection, storage, or use of private data or biological samples from living individuals by means of interactions, interventions, surveys, or other research methods or procedures.
Incidental finding: information inadvertently discovered during medical treatment or research which was not intentionally sought. For example, if a research subject receives an MRI as part of brain imaging study and the researcher notices an area in the fontal cortex that appears to be a tumor this information would be an incidental finding.
Individualized research results: in human subjects research, results pertaining to a specific individual in a study, such as the subject&rsquos pulse, blood pressure, or the results of laboratory tests (e.g. blood sugar levels, blood cell counts, genetic or genomic variants). Individualized results may include intended findings or incidental findings. There is an ongoing ethical controversy concerning whether, when, and how individualized research results should be shared with human subjects research. Some argue that individualized results should be returned if they are based on accurate and reliable tests and have clinical utility, because inaccurate, unreliable, or uncertain results may be harmful. Others claim that the principle of autonomy implies that subjects should be able to decide whether to receive their results.
Informed consent: the process of making a free and informed decision (such as to participate in research). Individuals who provide informed consent must be legally competent and have enough decision-making capacity to consent to research. Research regulations specify the types of information that must be disclosed to the subject. See also Assent.
Informed consent, blanket (general): a provision in an informed consent document that gives general permission to researchers to use the subject&rsquos data or samples for various purposes and share them with other researchers.
Informed consent, documentation: a record (such as a form) used to document the process of consent. Research regulations require that consent be documented however, an institutional review board may decide to waive documentation of consent if the research is minimal risk and 1) the principle risk of the study is breach of confidentiality and the only record linking the subject to the study is the consent form or 2) the research involves procedures that normally do not require written consent outside of the research context.
Informed consent, specific: a provision in an informed consent document that requires researchers to obtain specific permission from the subject prior to using samples or data for purposes other than those that are part of the study or sharing them with other researchers.
Informed consent, tiered: provisions in an informed consent document that give the subject various options concerning the use and sharing of samples or data. Options may include blanket consent, specific consent, and other choices.
Informed consent, waiver: in human subjects research, the decision by an institutional review board to waive (or set aside) some or all of the informed consent requirements. Waivers are not usually granted unless they are necessary to conduct the research and pose minimal risks to the subjects.
Institutional animal care and use committee (IACUC): a committee responsible for reviewing and overseeing animal research conducted at an institution. IACUCs usually include members from different backgrounds and disciplines, with institutional and outside members, scientists and non-scientists.
Institutional review board (IRB): a committee responsible for reviewing and overseeing human subjects research. An IRB may also be called a research ethics committee (REC) or research ethics board (REB). IRBs usually include members from different backgrounds and disciplines, with institutional and outside members, scientists and non-scientists.
Intellectual property: legally recognized property pertaining to the products of intellectual activity, such as creative works or inventions. Forms of intellectual property include copyrights on creative works and patents on inventions.
Justice: 1. treating people fairly. 2. An ethical principle that obligates one to treat people fairly. Distributive justice refers to allocating benefits and harms fairly procedural justice refers to using fair processes to make decisions that affect people formal justice refers to treating similar cases in the same way. In human subjects research, the principle of justice implies that subjects should be selected equitably. See also Belmont Report .
Kantianism: An ethical theory developed by German philosopher Immanuel Kant (1724-1804), which holds that the right thing to do is to perform one&rsquos duty for duty&rsquos sake. One&rsquos duty is defined by an ethical principle known as the categorical imperative (CI). According to one version of the CI, one should act according to a maxim that could become a rule for all people. According to another version, one should always treat people as having inherent moral value (or dignity) and never only as objects or things to be used to achieve some end.
Material transfer agreement (MTA): an agreement between institutions for the transfer and use of research materials, such as cells or reagents.
Media embargo: a policy, adopted by some journals, which allows journalists to have access to a scientific paper prior to publication, provided that they agree not to publicly disclose the contents of the paper until it is published. Some journals will refuse to publish papers that have already appeared in the media.
Mentor: someone who provides education, training, guidance, critical feedback, or emotional support to a student. In science, a mentor may be the student&rsquos advisor but need not be.
Minimal risk: a risk that is not greater than the risk of routine medical or psychological tests or exams or the risk ordinarily encountered in daily life activities.
Misconduct: See Research misconduct.
Mismanagement of funds: spending research funds wastefully or illegally for example, using grant funds allocated for equipment to pay for travel to a conference. Some types of mismanagement may also constitute fraud or embezzlement.
Morality (see Ethics).
Objectivity: 1. The tendency for the results of scientific research to be free from bias. 2. An ethical and epistemological principle instructing one to take steps to minimize or control for bias.
Observer (or Hawthorne) effect: the tendency for individuals to change their behavior when they know they are being observed. Some social science experiments use deception to control for the observer effect.
Openness: the ethical obligation to share the results of scientific research, including data and methods.
Office of Human Research Protections (OHRP): a federal agency that oversees human subjects research funded by the Department of Health and Human Services, including research funded by the National Institutes of Health. OHRP publishes guidance documents for interpreting the Common Rule, sponsors educational activities, and take steps to ensure compliance with federal regulations, including auditing research and issuing letters to institutions concerning non-compliance.
Office of Research Integrity (ORI): a U.S. federal agency that oversees the integrity of research funded by the Public Health Service, including research funded by the National Institutes of Health. ORI sponsors research and education on research integrity, and reviews reports of research misconduct inquiries and investigations from institutions.
Paternalism: restricting a person&rsquos decision-making for their own good. In soft paternalism, one restricts the choices made by someone who has a compromised ability to make decisions (see Decision-making capacity) in hard paternalism, one restricts the choices made by someone who is fully autonomous (see autonomy).
Patent: a right, granted by a government, which allows the patent holder to exclude others from making, using, or commercializing an invention for a period of time, typically 20 years. To be patented, an invention must be novel, non-obvious, and useful. The patent holder must publicly disclose how to make and use the invention in the patent application.
Peer review: The process of using experts within a scientific or academic discipline (or peers) to evaluate articles submitted for publication, grant proposals, or other materials.
Peer review, double-blind: a peer review process in which neither the authors nor the reviewers are told each other&rsquos identities.
Peer review, open: a peer review process in which the authors and reviewers are told each other&rsquos identities.
Peer review, single-blind: a peer review process, used by most scientific journals, in which the reviewers are told the identities of the authors but not vice versa.
Placebo: a biologically or chemically inactive substance or intervention given to a research subject which is used to control for the Placebo effect.
Placebo effect: a person&rsquos psychosomatic response to the belief that they are receiving an effective treatment. Researchers may also be susceptible to the placebo effect if they treat subjects differently who they believe are receiving effective treatment. See also Double-Blinding.
Plagiarism: misrepresenting someone else&rsquos creative work (e.g. words, methods, pictures, ideas, or data) as one&rsquos own. See also Research misconduct.
Plagiarism, self: reusing one&rsquos own work without proper attribution or citation. Some people do not view self-plagiarism as a form of plagiarism because it does not involve intellectual theft.
Politics: 1. Activities associated with governance of a country. 2. The science or art of government. 3. The study of government.
Precautionary principle (PP): an approach to decision-making which holds that we should take reasonable measures to prevent, minimize, or mitigate harms which are plausible and serious. Some countries have used the PP to make decisions concerning environmental protection or technology development. See also Risk/benefit analysis, Risk management.
Preponderance of evidence: in the law, a standard of proof in which a claim is proven if the evidence shows that it is more likely true than false (i.e. probability > 50%). Preponderance of evidence is the legal standard generally used in research misconduct cases. This standard is much lower than the standard used in criminal cases, i.e. proof beyond reasonable doubt.
Privacy: a state of being free from unwanted intrusion into one&rsquos personal space, private information, or personal affairs. See also Confidentiality.
Proprietary research: research that a private company owns and keeps secret.
Protocol: a set of steps, methods, or procedures for performing an activity, such as a scientific experiment.
Protocol, deviation: a departure from a protocol. In human subjects research, serious or continuing deviations from approved protocols should be promptly reported to the institutional review board.
Publication: the public dissemination of information. In science, publication may occur in journals or books, in print or electronically. Abstracts presented at scientific meetings are generally considered to be a form of publication.
Publication bias: bias related to the tendency publish or not publish certain types of research. For example, some studies have documented a bias toward publishing positive results.
Quality control/quality assurance: processes for planning, conducting, monitoring, overseeing, and auditing an activity (such as research) to ensure that it meets appropriate standards of quality.
Questionable research practices (QRPs): research practices that are regarded by many as unethical but are not considered to be research misconduct. Duplicate publication and Honorary authorship are considered by many to be QRPs.
Randomization: a process for randomly assigning subjects to different treatment groups in a clinical trial or other biomedical experiment.
Randomized controlled trial (RCT): an experiment, such as a clinical trial, in which subjects are randomly assigned to receive an experimental intervention or a control.
Regulation: 1. A type of law developed and implemented by a government agency. 2. The process of regulating or controlling some activity.
Reliance agreement: an agreement between two institutions in which one institution agrees to oversee human subjects research for the other institution for a particular study or group of studies.
Remuneration: in human subjects research, providing financial compensation to subjects.
Reproducibility: the ability for an independent researcher to achieve the same results of an experiment, test, or study, under the same conditions. A research paper should include information necessary for other scientists to reproduce the results. Reproducibility is different from repeatability, in which researchers repeat their own experiments to verify the results. Reproducibility is one of the hallmarks of good science.
Research: A systematic attempt to develop new knowledge.
Research compliance: See Compliance.
Research ethics: 1. Ethical conduct in research. 2. The study of ethical conduct in research. See Responsible conduct of research.
Research integrity: following ethical standards in the conduct of research. See Research ethics.
Research institution: an institution, such as a university or government or private laboratory, which is involved in conducting research.
Research integrity official (RIO): an administrator at a research institution who is responsible for responding to reports of suspected research misconduct.
Research misconduct: intentional, knowing, or reckless behavior in research that is widely viewed as highly unethical and often illegal. Most definitions define research misconduct as fabrication or falsification of data or plagiarism, and some include other behaviors in the definition, such as interfering with a misconduct investigation, significant violations of human research regulations, or serious deviations from commonly accepted practices. Honest errors and scientific disputes are not regarded as misconduct.
Research misconduct, inquiry vs. investigation: If suspected research misconduct is reported at an institution, the Research integrity official may appoint an inquiry committee to determine whether there is sufficient evidence to conduct an investigation. If the committee determines that there is sufficient evidence, an investigative committee will be appointed to gather evidence and interview witnesses. The investigative committee will determine whether there is sufficient evidence to prove misconduct and make a recommendation concerning adjudication of the case to the research integrity official.
Research record: a record related to the planning, review implementation, or dissemination of research, including, but not limited to: data, protocols, standard operating procedures, manuscripts, grant proposals, and communications with funders, journals, or approval committees.
Research sponsor: an organization, such as a government agency or private company, which funds research.
Research subject (also called research participant): a living individual who is the subject of an experiment or study involving the collection of the individual's private data or biological samples (see also human subjects research).
Respect for persons: a moral principle, with roots in Kantian philosophy, which holds that we should respect the choices of autonomous decision-makers (see Autonomy, Decision-making capacity) and that we should protect the interests of those who have diminished autonomy (see Vulnerable subject). See also Belmont Report.
Responsible conduct of research (RCR): following ethical and scientific standards and legal and institutional rules in the conduct of research. See also Research ethics, Research integrity.
Retraction: withdrawing or removing a published paper from the research record because the data or results have subsequently been found to be unreliable or because the paper involves research misconduct. Journals publish retraction notices and identify retracted papers in electronic databases to alert the scientific community to problems with the paper. See Correction.
Right: a legal or moral entitlement. Rights generally imply duties or obligations. For example, if A has a right not be killed then B has a duty not to kill A.
Risk: the product of the probability and magnitude (or severity) of a potential harm.
Risk/benefit analysis: a process for determining an acceptable level of risk, given the potential benefits of an activity or technology. See also Risk Management, Precautionary Principle.
Risk management: the process of identifying, assessing, and deciding how best to deal with the risks of an activity, policy, or technology. See also Precautionary principle.
Risk minimization: in human subjects research, the ethical and legal principle that the risks to the subjects should be minimized using appropriate methods, procedures (such as Subject selection rules), or other safety measures (such as a Data and safety monitoring board).
Risks, reasonable: in human subjects research, the ethical and legal principle that the risks to the subjects should be reasonable in relation to the benefits to the subjects or society. See Risk/benefit analysis, Social value.
Salami science: dividing a scientific project into the smallest papers that can be published (least publishable unit) in order to maximize the total publications from the project. See Questionable research practices.
Scientific (or academic) freedom: the institutional and government obligation to refrain from interfering in the conduct or publication of research, or the teaching and discussion of scientific ideas. See Censorship.
Scientific validity (or rigor): processes, procedures, and methods used to ensure that a study is well-designed to test a hypothesis or theory.
Self-deception: in science, deceiving one&rsquos self in the conduct of research. Self-deception is a form of bias that may be intentional or unintentional (subconscious).
Self-regulation: regulation of an activity by individuals involved in that activity as opposed to regulation by the government. See also Law.
Singapore Statement: an international research ethics code developed at the 2nd World Conference on Research Integrity in Singapore in 2010.
Social responsibility: in science, the obligation to avoid harmful societal consequences from one&rsquos research and to promote good ones.
Social value: 1. the social benefits expected to be gained from a scientific study, such as new knowledge or the development of a medical treatment or other technology. 2. The ethical principle that human subjects research should be expected to yield valuable results for society.
Speciesism: the idea, defended by philosopher Peter Singer, that treating human beings as morally different from animals is a form of discrimination similar to racism. Singer argues that since all animals deserve equal moral consideration, most forms of animal experimentation are unethical. See Value, scale of.
Standard operating procedures (SOPs): rules and procedures for performing an activity, such as conducting or reviewing research.
Statistical significance: a measure of the degree that an observed result (such as relationship between two variables) is due to chance. Statistical significance is usually expressed as a p-value. A p-value of 0.05, for example, means that the observed result will probably occur as a result of chance only 5% of the time.
Subject selection: rules for including/excluding human subjects in research. Subject selection should be equitable, i.e. subjects should be included or excluded for legitimate scientific or ethical reasons. For example, a clinical trial might exclude subjects who do not have the disease under investigation or are too sick to take part in the study safely. See Risk minimization, Justice.
Surrogate decision-maker: see Legal authorized representative.
Testability: the ability to test a hypothesis or theory. Scientific hypotheses and theories should be testable.
Therapeutic misconception: 1. The tendency for human subjects research in clinical research to believe that the study is designed to benefit them personally 2. The tendency for the subjects of clinical research to overestimate the benefits of research and underestimate the risks.
Three Rs: ethical guidelines for protecting animal welfare in research, including reduction (reducing the number of animals used in research), replacement (replacing higher species with lower ones or animals with cells or computer models), and refinement (refining research methods to minimize pain and suffering).
Transparency: in science, openly disclosing information that concerned parties would want to know, such as financial interests or methodological assumptions. See also Conflict of interest, management.
Tuskegee Syphilis Study: a study, sponsored by the U.S. Department of Health, Education, and Welfare, conducted in Tuskegee, Alabama from 1932-1972, which involved observing the progression of untreated syphilis in African American men. The men were not told they were in a research study they thought they were getting treatment for &ldquobad blood.&rdquo Researchers also steered them away from clinics where could receive penicillin when it became available as a treatment for syphilis in the 1940s.
Unanticipated problem (UP): an unexpected problem that occurs in human subjects research. Serious UPs that are related to research and suggest a greater risk of harm to subjects or others should be promptly reported to institutional review boards and other authorities.
Undue influence: taking advantage of someone&rsquos vulnerability to convince them to make a decision.
Utilitarianism: An ethical theory which holds that the right thing to do is to produce the greatest balance of good/bad consequences for the greatest number of people. Act utilitarians focus on good resulting from particular actions while rule utilitarians focus on happiness resulting from following rules. Utilitarians may equate the good with happiness, satisfaction of preferences, or some other desirable outcomes. See also Consequentialism, Ethical theory.
Value: something that is worth having or desiring, such as happiness, knowledge, justice, or virtue.
Value, conflict: an ethical-dilemma involving a conflict among different values.
Value, instrumental: something that is valuable for the sake of achieving something else, e.g. a visit to the dentist is valuable for dental health.
Value, intrinsic: something that is valuable for its own sake, e.g. happiness, human life.
Value, scale of: the idea that some things can be ranked on a scale of moral value. For example, one might hold that human beings are more valuable than other sentient animals sentient animals are more valuable than non-sentient animals, etc. Some defenders of animal experimentation argue that harming animals in research can be justified to benefit human beings because human beings are more valuable than animals.
Virtue: a morally good or desirable character trait, such as honesty, courage, compassion, modesty, fairness, etc.
Virtue ethics: an ethical theory that emphasizes developing virtue as opposed to following rules or maximizing good/bad consequences.
Voluntariness: the ability to make a free (un-coerced) choice. See Coercion, Informed consent.
Vulnerable subject: a research subject who has an increased susceptibility to harm or exploitation due to his or her compromised ability to make decisions or advocate for his/her interests or his/her dependency. Vulnerability may be based on age, mental disability, institutionalization, language barriers, socioeconomic deprivation, or other factors. See Decision-making capacity, Informed consent.
Whistleblower: a person who reports suspected illegal or unethical activity, such as research misconduct or non-compliance with human subjects or animal regulations. Various laws and institutional policies protect whistleblowers from retaliation.