Reproducibility in Scientific Research

Explain why basic researchers often employ quality principles in their work even when not required by law

Basic researchers use quality principles—even when not legally required—because these practices make their experiments more reliable, reproducible, and credible.

What is the big deal about reproducibility?

Reproducibility is a big deal because science only works if results can be repeated and verified by others.

What can happen if an experiment was never re-tested to see if the results were reproducible?

If an experiment is never re-tested, false or flawed results might be accepted as true, leading to incorrect conclusions, wasted resources, and future research built on an unreliable foundation.

What happened in Begley & Ellis’s review of experiments published about Cancer Biology?

Begley & Ellis reviewed major cancer biology studies and found that most of the experiments could not be successfully reproduced, even though they were published in top journals. This highlighted serious problems with reliability and data integrity in high-impact cancer research.

What happened as a result of Amgen and Bayer’s reports?

Amgen and Bayer’s reports showing that many published studies couldn’t be reproduced pushed the scientific community to take the reproducibility crisis seriously. As a result, journals, funding agencies, and researchers began adopting stronger quality controls—like better documentation, stricter experimental standards, and requirements for independent replication.

Amgen and Bayer’s reports- Why didn’t they have more impact?

Amgen and Bayer’s reports didn’t have more impact because the companies didn’t reveal which specific studies failed to reproduce, making it hard for the scientific community to investigate or correct the problems. Without transparency, their findings raised concern but couldn’t trigger targeted changes.

What are some ways the government and publishers are attempting to keep HARKing at a minimum?

Amgen and Bayer’s reports didn’t have more impact because the companies didn’t reveal which specific studies failed to reproduce, making it hard for the scientific community to investigate or correct the problems. Without transparency, their findings raised concern but couldn’t trigger targeted changes.

What is a single-blinded study?

The participant doesn’t know which group they’re in (treatment or control), but the researcher does

What is a double-blinded study?

Neither the participant nor the researcher knows who is receiving the treatment, reducing bias on both sides and making the results more reliable.

What are some ways we can avoid creating irreproducible results?

We can avoid creating irreproducible results by using clear protocols, keeping detailed records, controlling variables carefully, using proper sample sizes, reducing bias with blinding, repeating experiments, sharing data and methods openly, and having independent teams verify results.

What does it mean to use standards in the lab?

Using standards in the lab means working with known reference materials or procedures so you can compare your results against something reliable. Standards help ensure accuracy, consistency, and that your measurements are truly reflecting what you think they are.

What are null results?

Null results are outcomes where the experiment shows no significant effect or no difference between groups, meaning the hypothesis isn’t supported—but the result is still scientifically valuable.

Why should null results be able to be published just as well as other experimental results?

Null results should be publishable because they prevent other scientists from repeating the same failed experiments, reduce bias toward “positive” findings, give a more accurate picture of what actually works, and help strengthen the overall reliability of scientific research.

Define “Good science”

“Good science” means research that is careful, honest, well-designed, reproducible, and based on solid evidence. It follows quality principles, minimizes bias, and produces results that other scientists can trust and verify.

Define transparency

Transparency means openly sharing how a study was done—its methods, data, materials, and reasoning—so others can understand, evaluate, and replicate the work accurately.

Define HARKing

HARKing (Hypothesizing After the Results are Known) is when a researcher looks at their results first and then creates a hypothesis that fits those results, pretending it was their original prediction—leading to misleading or biased science.

Define blinding

is a research technique where participants, researchers, or both are kept unaware of which group receives the treatment to prevent bias from affecting the results.

Define preregistration

means writing down your study plan—your hypothesis, methods, and analysis—before doing the experiment, then publicly time-stamping it so you can’t change your plan later to make the results look better.

What is validation?

Validation is the process of confirming that a method, instrument, or experiment actually measures what it’s supposed to measure and produces accurate, reliable results.

what type of things are often validated?

Things often validated include lab methods, instruments, assays, software, protocols, and measurement tools to make sure they work correctly and give reliable, accurate results.

How can you validate people, equipment or reagents?

You can validate people by training and testing their competence, validate equipment by checking calibration and performance against known standards, and validate reagents by verifying purity, stability, and that they produce correct, expected results in control experiments.

What is a cleanroom and how would an employee dress properly to work in one?

A cleanroom is a controlled environment with very low levels of dust, microbes, and other contaminants. To work in one, employees wear special cleanroom gear—like gowns, gloves, shoe covers, hairnets, masks, and sometimes full coveralls—to prevent particles from their body or clothing from contaminating the space.

How does air have to be controlled for work in a cleanroom to avoid contamination?

Air in a cleanroom must be tightly controlled using HEPA-filtered airflow, positive air pressure, and constant air exchanges so that clean air flows in, contaminated air is pushed out, and particles or microbes can’t settle on products or surfaces.

How do you handle raw materials in the lab/facility?

Raw materials should be received, inspected, labeled, stored properly, and handled using clean, controlled procedures. They must be tracked with documentation, checked for quality, and only used if they meet specifications to prevent contamination or mix-ups.

Define inputs

Inputs are the materials, resources, or information that go into a process or experiment to produce a result—such as reagents, equipment, data, and trained personnel.

Define outputs

Outputs are the final products, results, or data that come out of a process after inputs have been used—such as experimental results, finished materials, or completed reports.

How can specification differ for a product (such as salt, or glycerol)

Specifications can differ for the same product—like salt or glycerol—because different uses require different purity levels, concentrations, grades, or allowable contaminants. For example, “table salt,” “lab-grade salt,” and “pharmaceutical-grade salt” all have different specifications depending on how pure and controlled they need to be.

What are critical points/control points?

Critical points (or control points) are specific steps in a process where things can easily go wrong and affect quality or safety, so they must be closely monitored and controlled to prevent errors or contamination.

What are examples of PAT?

Examples of PAT (Process Analytical Technology) include real-time sensors, in-line pH meters, temperature probes, NIR spectroscopy, HPLC systems, dissolved oxygen sensors, and automated mixing or monitoring systems used to track and control a process while it’s happening.

What does it mean to be qualified?

means you have the training, skills, and demonstrated ability to perform a specific task or use certain equipment correctly and safely.

What is an installation qualification?

Confirms that equipment is installed correctly according to manufacturer specs (right location, utilities, parts, and setup).

What is an operational qualification?

Confirms the equipment works properly and performs within expected limits under normal operating conditions.

How is a deviation different from a nonconformance?

A deviation is when you don’t follow a planned procedure, while a nonconformance is when a product or result fails to meet specifications.

What are permissible limits for a control limit?

Permissible limits for a control limit are the maximum and minimum values a process can reach and still be considered “in control.”

What are quality systems in a lab? Why do we need them?

are the organized policies, procedures, and controls that ensure work is done accurately, safely, and consistently. We need them to prevent errors, protect data integrity, meet regulatory expectations, and make sure results are reliable and reproducible.

What happened in the Barr Industries inspection?

the FDA found widespread quality failures—like poor recordkeeping, incomplete testing, ignored out-of-spec results, and employees retesting samples until they “passed.” These violations showed that Barr’s QC system wasn’t trustworthy, leading to major regulatory action and stricter expectations for the entire industry.

Define Quarantine

Holding materials, products, or equipment aside so they cannot be used until they pass inspection or testing.

Define Specifications

Detailed requirements or criteria a material, product, or process must meet to be accepted (e.g., purity, concentration, appearance).

Define In-process Testing

Tests performed during manufacturing to make sure the process is working correctly before the final product is made.

Define nonconformance

A product or result that fails to meet specifications and therefore cannot be accepted.

Define Deviation

When a procedure or process is not followed as written, either accidentally or intentionally.

Define PAT

Tools and systems that monitor and control a process in real time, such as sensors, spectroscopy, pH probes, or automated analyzers.

Define Downstream processing

All the steps taken after fermentation or production to purify and finish a product—like filtration, chromatography, and drying.

Define Critical control points

Steps in a process where contamination or errors are most likely to occur, requiring strict monitoring to keep the process safe and consistent.

Define Aseptic processing

Manufacturing done in conditions designed to prevent microbial contamination, usually in cleanrooms using sterile equipment and strict technique.

Define HEPA

A specialized filter that removes 99.97% of particles ≥0.3 microns, used for cleanrooms and sterile airflow.

Define OOS

A test result that falls outside the approved specification limits, triggering an investigation.

Define Worst case challenge

Testing a system, method, or process under the maximum stress or most difficult conditions it might encounter to prove it still works reliably.

What are the advantages & disadvantages of a large molecule drug over a small molecule drug?

Large molecule drugs are more specific and effective for complex diseases but are costly, unstable, and usually require injection instead of oral dosing.

What are some of the current issues facing biopharmaceuticals today?

Current issues in biopharmaceuticals include high production costs, complex manufacturing, cold-chain storage needs, regulatory challenges, difficulty scaling up, shortages of skilled workers, and safety concerns like contamination or immune reactions.

What are the stages along the pharmaceutical lifecycle?

The pharmaceutical lifecycle includes discovery, preclinical testing, clinical trials (Phase I–III), regulatory review and approval, manufacturing and scale-up, marketing and distribution, and finally post-market monitoring (Phase IV) to track safety and effectiveness.

What is an API?

An API (Active Pharmaceutical Ingredient) is the main chemical or biological substance in a drug that produces the intended therapeutic effect.

What is HTS and why might a company use this?

HTS (High-Throughput Screening) is a technology that rapidly tests thousands to millions of compounds to find ones that affect a biological target. Companies use HTS to speed up drug discovery, identify promising leads faster, and reduce the time and cost of finding new medicines.

Compare and contrast clinical and preclinical development

Preclinical development uses lab and animal studies to assess safety before human testing, while clinical development tests the drug’s safety and effectiveness in people.

What are pharmacokinetics? (ADME)

Pharmacokinetics (ADME) describes how a drug is Absorbed, Distributed, Metabolized, and Excreted by the body.

What is the difference between a NDA and an IND?

An IND(Investigational New Drug) allows a company to begin testing a new drug in humans, while an NDA(New Drug Application) is the final request asking the FDA to approve the drug for public use after all studies are complete.

What is the difference between a NDA and ANDA(Abbreviated New Drug Application)?

An NDA provides full data to prove a new drug’s safety and effectiveness, while an ANDA shows that a generic drug is bioequivalent to an already approved product without repeating full clinical trials.

What is the purpose of an IRB?

An IRB (Institutional Review Board) protects human research participants by reviewing studies to ensure they are ethical, safe, and compliant with regulations.

Describe cGLPs

are regulations that ensure nonclinical lab studies are planned, performed, documented, and reported with high quality so the data used to support drug safety is reliable and trustworthy.

Describe cGMPs

are regulations that ensure drugs are consistently made, controlled, and tested to high-quality standards so every batch is safe, pure, and effective.

What are some characteristics of a drug you might study in preclinical development?

you study a drug’s toxicity, mechanism of action, dosage range, pharmacokinetics (ADME), biological activity, and potential side effects before testing it in humans.

What are generics and how do they fit into this pharmaceutical lifecycle?

are copies of brand-name drugs that have the same active ingredient and performance, and they enter the pharmaceutical lifecycle after the original drug’s patent expires, providing cheaper alternatives without needing full clinical trials.

What are the ways the FDA can speed up getting a potential drug to market?

can speed up getting a drug to market through Fast Track, Breakthrough Therapy, Accelerated Approval, and Priority Review, all of which shorten review times or allow earlier approval based on promising evidence.

Calcitonin-What is the largest center in the FDA?

The largest center in the FDA is CDER — the Center for Drug Evaluation and Research, which oversees prescription drugs, OTC drugs, and many biologics.

Calcitonin-Which disease is calcitonin treating?

is used to treat osteoporosis (especially in postmenopausal women) and Paget’s disease of bone by helping lower blood calcium levels and slow bone breakdown.

Calcitonin-What is the first treatment doctors will give for this disease?

For osteoporosis, doctors usually give bisphosphonates (like alendronate or risedronate) as the first-line treatment before considering calcitonin.

Calcitonin-How much better is salmon calcitonin than human calcitonin?

Salmon calcitonin is about 40–50 times more potent than human calcitonin, which is why it’s used therapeutically.

Calcitonin-What form of drug is calcitonin? (how do you take it?)

is taken as a nasal spray or as a subcutaneous injection.

Calcitonin-How long must a company wait once submitting their INDA before starting clinical trials?

A company must wait 30 days after submitting their IND before beginning clinical trials, unless the FDA places the study on hold.