What is Pathology and What Does a Pathologist Do?

A pathologist is a medical professional who examines bodies and body tissue. They are also responsible for conducting lab tests. A clinical pathologist is an essential part of medical teams who reach diagnoses for patients. After completing medical school, an individual must also complete three years of advanced medical education in a residency program before they are eligible to take board certification exams. Most pathologists are trained in both anatomical and clinical pathology.

The Role of Blood and Pathology Tests

Blood and pathology tests are essential for detecting, diagnosing, and treating disease. The term, “pathology” means the study of disease as well as causes and progression. There are a variety of pathology tests including blood tests, urine, stool (feces), and body tissue testing. Pathologists interpret the results of blood and pathology tests. They are looking for abnormalities in the samples that may indicate the presence of disease or health risks like cancer, chronic illnesses, or pre-diabetes. 

Why Blood and Pathology Tests Are Ordered

While pathology plays a role in detecting and diagnosing diseases, the tests are also important for other reasons including:

·   Properly treating a disease

·   Monitoring the progression of disease

·   Preventing disease

·   Determining the future risk of disease

·   Aiding research for new treatment options

·   Ensure the safety of treatment and procedures

When a doctor or specialist requests pathology tests it’s usually due to a concern about your health risks. A pathology test is effective for discovering if a problem or concern exists.

Types of Tissue Pathologists Examine

A pathologist is trained to examine tissue samples including samples as small as a dozen cells. Tissue cells may be obtained by aspiration or a needle biopsy. Larger tissue samples are surgically removed.

What do clinical pathologists do?

A clinical pathologist examines blood, urine, and other types of bodily fluids under a microscope. They are watching for the presence of certain chemicals or other substances. Their test results often determine a diagnosis or treatment option. Specimens used in clinical pathology include:

·   Blood Samples are used in many tests and can be checked in a variety of ways whole, plasma (the remaining fluid after red and white blood cells are removed), or serum (the clear fluid that separates from the blood during clotting).

·   Urine Samples are collected in a variety of ways including catheterization, clean catch specimen, or randomly.

·   Sputum Samples or phlegm samples are coughed into a clean container.

·   Stool Samples are often examined for the presence of blood.

·   Other Bodily Fluid Samples may include spinal fluid, pleural fluids, belly fluids, joint fluids, or bone marrow.

Clinical pathologists are often responsible for blood banks at hospitals. Their duties include collecting and processing blood products. They may also look at transfusion reactions or check tissue compatibility for transplants.

Conclusion

Pathology is a medical field that is quickly becoming more specialized. Pathologists provide experience and expertise when it comes to interpreting laboratory test results and evaluating cells, tissue, and organs in order to diagnose disease. A pathologist may determine a specific type of cancer and what stage it is in so that appropriate treatment can be recommended. In a quickly advancing technological age, their work is far from done and their importance continues to become apparent.

https://www.mskcc.org/cancer-care/diagnosis-treatment/diagnosing/role-pathology

https://pathology.uic.edu/understanding-your-pathology-report/

https://www.rcpath.org/discover-pathology/what-is-pathology.html

https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=85&contentid=P00955

https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/Blood-and-pathology-tests

https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/the-pathologist

5 Laws That Apply to Biorepositories

With the increase of biological and pharmaceutical research, biorepositories are surfacing as a huge, important component. Biorepositories store and catalog a variety of biological samples. They must adhere to stringent regulations when handling and using biological specimens, especially when human samples are involved. Here are some of the legal guidelines biorepository staff much be familiar with and adhere to.

HIPAA Compliance

HIPAA or the Health Insurance Portability and Accountability Act is a US law. It is designed to protect patient’s medical records and privacy. Any business that handles any type of patient information much follow HIPAA regulations and practices to protect patient privacy. Biorepositories store samples were taken from human patients. If there is a breach in patient data or if the biorepository is not compliant with the guidelines set forth in HIPAA, they can be subject to criminal or civil penalties.

Informed Consent and Human Tissue Samples

The IRB (Institutional Review Board) oversees studies at research institutions when they involve human subjects. The review board is set up to help protect people from possible negative consequences when they are involved in research studies. In most cases, specimens collected from research participants or patients require the signing of an informed consent form approved by the IRB. Specimens are often stored in biorepositories for future use. These specimens require signed informed consent documents. It is often difficult to know when specimens will be used in research, donors may be able to withdraw their authorization for tissue sample use.

Patient’s Right to Withdraw from Research

When patients consent to the use of their samples for future research, they retain their right to withdraw that consent. As far as sample management and protocol in general, it can vary between institutions. Biorepositories should outline their best practices and how the specimens will be handled in cases where a patient withdraws consent. For instance, biorepositories may choose to destroy the sample, or they may be able to transfer the sample to a different donor-approved research project. Having a transparent operating procedure to follow for cases where donors withdraw consent, helps protect biorepositories from unintentional violations of HIPAA or IRB regulations.

Custody and Ownership of Samples

The laws vary from state to state and between institutions as they pertain to biological repository sample ownership and custody. In most cases, collected samples are owned by the organization that gathered them. Researchers who collect samples usually retain custody of them since they are using them for a particular study or purpose. Other times, they are in the custody of an IRB-approved biospecimen regulatory body. Biorepositories should have clearly stated guidelines for the ownership, custody, and distribution of samples. They should also have a clear plan for cases when a researcher leaves their institution.

Access to Biological Specimens and Data

Biorepositories also need to tightly control access to biological samples and the data associated with them. This helps ensure both the integrity and security of the specimen. Access to samples should be limited to authorized researchers and specific biorepository staff. Logs should be diligently maintained by biorepository staff. These logs should contain detailed audit trails for each sample including access logs.

Biological research is growing rapidly and as with other technologies, the pace is often faster than regulations. Laws that affect biorepositories are still relatively young and it’s likely that they will change as products, research, and technology continue to advance. Staff members at biorepositories should continue to be aware of regulatory developments as they occur in the future.

Custom Collection Services

What is a Biorepository?

A biorepository is an organization that collects, processes, stores, and distributes tissue samples for clinical research or other scientific investigations. They assist in maintaining and managing specimens such as tissue samples from humans, animals and other living organisms. A biorepository functions to maintain biospecimens, collect relevant information and assure the quality of the samples in their collection. They follow standard operating procedures (SOPs) that reduce anomalies in samples and which also provide guidelines for storage and maintenance. SOPs also ensure that biospecimens collected closely resemble that of their natural state. It helps biorepositories maintain a standardized framework for conducting operations and allows for the seamless implementation of processes.

What is Custom Procurement?

Some biorepositories, like Geneticist Inc., provide custom tissue procurement. This means that they are able to provide custom collection of biofluids, tissue samples, and blood samples in various specialties such as gastroenterology, oncology, rheumatology, neurology, and dermatology. Biorepositories that offer custom collection services have the ability to collect from a vast range of medical procedures such as elective skin biopsies, resections, autopsies, endoscopies, blood draws, and more. Due to the nature of the collection processes and procedures, biorepositories need to have a skilled logistics team and an expert medical courier network. The custom procurement of biospecimens is important especially if:

• Fresh collections are required

• There is a necessity for matched tissue pairs

• Rare indications or specific specimens

• The need for specific procedures during the collection and processing of samples

• Active cases and autopsies are needed

• The study or research is complicated

Examples of Biospecimens

• Biofluids – Examples of biofluids include stool, urine, whole blood, serum, plasma, cerebrospinal fluid, saliva, sputum, and swabbed material. Biofluids can be available frozen or fresh. Depending on client preference, it can be with or without additives.

• Tissue – Some examples of human tissue include fresh tissue, fixed tissue, frozen tissue, formalin-fixed paraffin-embedded (FFPE) blocks, whole tissue samples, stained slides, unstained slides, tissue microarrays, and more. These samples can be annotated with the proper genetic and molecular characterizations, outcomes data, pathology reports, and patient characteristics.

• Cells – Some research may require frozen or fresh cells that are still viable. These cells can be isolated from peripheral blood, cord blood, and bone marrow of normal donors and those with disease. Some examples include myeloid cells, pluripotent stem cells, mononuclear cells, and lymphoid cells.

What to Look For?

There are several factors that help decide which biorepository to go with when custom collection services are needed. Some of the factors that can help decide are:

a)       Procurement format options

Since prospective collection enable clients to decide which elements fit their needs, a custom procurement format can be designed with the help of our experienced team of scientists. Depending on the need of clients, custom procurement of biofluids, fresh tissue, frozen tissue, and more are available. Clients can also set the exclusion and inclusion criteria for specimens and donors.

b)      Partnerships

It is important to look for a biorepository that has a vast network of clinical partners to help ensure the highest quality of required biospecimen collection. It would also increase the access to more human tissue samples in various formats.

c)       Team members

A biorepository with experienced and certified team members would be the best choice as they would be well-trained with the ability to better understand the needs of researchers and to help find better solutions if necessary. With a great team on hand, specimens are more likely to be of the highest quality and fulfill the requirements of clients.

d)      Quality assurance

It is important for the biorepository to perform quality control checks to ensure that specimens are of the highest quality. This means that the staff should understand the appropriate storage or procurement procedures and ensure that the SOPs are adhered to strictly.

e)      Consent and privacy

Biorepositories should follow the procedures and guidelines during the procurement of human tissue samples. Informed consent and privacy of the donors should be of the highest priority to protect their interests.

Why Geneticist?

For custom collection services, the staff at Geneticist can design custom collections of a wide variety of biospecimens. Our staff are certified, experienced, and highly trained. Geneticist is a biorepository that is compliant with the Institutional Review Board (IRB) standards and provides the highest quality of collections. All our biospecimens and material adheres to the official protocols and is approved by the IRB and Independent Ethical Committee (IEC). Geneticist operates in accordance with current Federal Regulations, Health Insurance Privacy and Portability Act (HIPAA) and International Conference on Harmonisation – Good Clinical Practice (ICH-GCP) guidelines. With the proper inventory management process and extensive procurement formats, Geneticist strives to fulfill client requirements and satisfaction.

CTM Logistics

Introduction to CTM Logistics

Clinical trial materials (CTM) logistics is an important business that manages the transport and delivery of biospecimens and tissue samples. The business of tissue preservation, meeting demands, and shipping these specimens from places like a biorepository to their destinations does not come without challenges.

Challenges facing CTM Logistics

Besides the conventional logistics and supply-chain challenges, those involved in CTM logistics also face:

1)      Standards

Many countries do not have standard protocols for the entry of trial supplies. Due to the demands of clinical materials worldwide, the challenge of shipping CTMs include the extraordinary constraints of import and export.

2)      Notice

Those involved in CTM logistics have very little to no notice when it comes to knowing when the materials need to be shipped out. The issue of material suppliers being disconnected can also cause delays at trial sites due to a supply chain issue.

3)      Product Standards

There are many trials that need both comparator or placebo drugs along with the trial drug. However, these trials are usually “randomized” throughout the course of the trial. This means that different labels will be needed for different trial protocols or different locations.

4)      Handling and Transport

Since the quality of these materials can be affected during handling and transport, companies involved in CTM logistics need to have the equipment and manpower that are suited to deal with the supplies.

5)      End Users

There is also the issue where some end users (such as researchers and physicians who conduct trials at investigator sites) who are not trained supply chain managers.

6)      Cost

Companies providing CTM logistics services also have a high risk of overrunning their cost due to difficulty addressing all cost drivers, inefficiencies in the system, and potential expenses when corrective actions need to be taken.

7)      Communication

Just like any other field, poor communication and coordination of the supply chain can result in action gaps, duplication of efforts, and delays. Frequent plan revisions are required if there are errors.

8)      Circumstances

Many studies often face the risk of delays and the need to lengthen their timeline in situations where there is the unexpected expiration of products or out of stock situations.

The industry has adapted to some of the challenges and constraints over the years. Although the clinical trials can be affected by issues in the supply chain, the successful completion of these researches has led to the better diagnosis, therapy, and prevention of diseases.

Supply Chain Stages

The following are critical supply chain stages:

• Planning: Those that are responsible forecast and come up with a strategy.

• Sourcing: This is done to acquire the necessary materials such as ancillary supplies, drugs, and lab materials.

• Manufacturing: Once ready, the necessary packaging and labels that are needed are manufactured.

• Storage: The CTMs are stored in the appropriate condition using the proper equipment (if needed).

• Distribution: The CTMs are imported or exported according to local authority regulations.

• Site: The CTMs are stored, samples managed, and data processed.

• Return: The company manages the shipment along with final CTM reconciliation.

• Destruction: The CTMs are recycled or destroyed accordingly.

• Analytics: All accumulated data are processed and analyzed.

Training

Individuals who are interested in positions such as clinical supply chain managers or supervisors and those interested or new to the CTM industry. Employees that go through special training pertaining to CTMs are more efficient in their duties in the company and industry. They learn about:

• The overview of the supply chain from beginning to end

• The appropriate packaging and labeling that suits the needs of a specific study design

• Having a plan of action to prepare the materials

• Implementing their plan and troubleshooting

• The logistics involved for distribution of CTM to trial sites that are located worldwide

• How to outsource vendors for the labeling and packaging purposes

• Interactive Response Technology

• The different roles of their team members and their expectations for the CTM group

• Current Good Manufacturing Practices (cGMP)

• The implementation of cGMP in the packaging process

Services

The company that is in charge of CTM logistics generally provides services for:

• The receiving, storage, and distribution of the materials

• Obtaining the necessary import and export licenses from the authorities

• Acquiring custom clearance for the CTM

• Data management (verification, validation, query, tracking, coding for diseases or medications, result presentation)

• Biostatistics (Statistical analysis, writing, result presentation, and more)

• Importing and exporting CTMs

• Short or long-term storage of specimens

Conclusion

More clinical trials are conducted globally. This creates a significant logistical challenge as the management of CTMs and the supply chain require tactical knowledge and a vast commitment of resources to avoid delays. There are many who would find that it is much more efficient to hire CTM service providers to manage the logistics as there are many challenges in this industry.

References:

1)      Basta N. Clinical trial logistics capabilities are expanding. Pharmaceutical Commerce. Accessed 9/5/2018. http://pharmaceuticalcommerce.com/clinical-operations/clinical-trial-logistics-capabilities-are-expanding/

2)      CTM logistics. Geneticist. Accessed 9/5/2018. https://www.geneticistinc.com/ctm-logistics/

3)      Clinical research services: clinical logistics. Parexel. Accessed 9/5/2018. https://www.parexel.com/files/6714/1155/2827/CLS_Supply_Chain_Poster_Sept14.pdf

4)      Clinical trial materials training course. ISPE. Accessed 9/5/2018. https://ispe.org/training/classroom/clinical-trial-materials

Types of Biorepositories

Introduction

A biorepository is a center that functions to collect, process, store, and distribute tissue samples or specimens to support future research. These tissue samples can be sourced from humans or animals. The biorepository is responsible for maintaining the quality, accessibility, and distribution of these tissue samples.

Operations

• Upon delivery the tissue samples are recorded all information regarding the sample details are keyed into the laboratory information management system.

• Biospecimens are then processed to ensure consistency of the samples. Proper tissue preservation methodology is absolutely crucial to a biorepository.

• These specimens are then stored and held in their appropriate conditions. Sample holding boxes and freezers are sometimes used, however it depends on the storage requirements. For example Formalin-fixed paraffin-embedded tissue blocks can be stored at room temperature.

• Distribution involves retrieving the required samples from the inventory.

Standard Operating Procedures

Standard operating procedures (SOPs) are important for biorepositories as they help in the following:

• Reduce problematic variables within the samples,

• Ensure that biospecimens resemble specimens in their natural state,

• Provide standards on how operations should be conducted.

Types and Uses of Biorepositories

There are many different types of biorepositories that exist. Some help with biomarker validation, and others are integrated with registries. Most biorepositories are focused on collecting biospecimens for specific diseases. Others function to identify genetic clues that can aid in the guidance of therapeutic development. Similair to disease-focused biorepositories there are those  focused on the understanding of practices and habits. Biorepository sponsors can also vary. While some are funded as part of research to aid in the collection of specimens from participants, some are sponsored by organizations or medical centers to collect, process, and store samples from a wide variety of patients. Some biorepositories are organized by patient advocacy organizations to help kick-start research of specific diseases.

Examples

1. The Alzheimer’s Disease Neuroimaging Initiative – is a disease-focused biorepository and biomarker validation program that uses the samples and data collected from Alzheimer’s disease patients and patients with other forms of memory impairment.

2. The Health Outreach Program for the Elderly (HOPE) is a biorepository at Boston University that supports multiple studies. The HOPE registry follows up with their Alzheimer’s patients annually.

3. The United Kingdom Biobank is a biorepository with a broad focus. They aim to improve the diagnosis, treatment, and prevention of various diseases such as cancer, stroke, diabetes, heart disease, eye disorders, depression, dementia, and arthritis. In between 2006 to 2010, they managed to recruit half a million individuals between the ages of 40 to 69. Samples such as blood, saliva, and urine have been donated for analysis. These participants have also provided detailed personal information and consented to future follow up for many years to help researchers discover how various diseases develop.

4. The Autism Research Resource is sponsored by the state of New Jersey to research autism in families where more than one child is affected.

5. The Centers for Disease Control (CDC) Cell and DNA Repository use samples from transformed cell lines available through the Genetic Testing Reference Material Coordination Program. Some of the samples obtained are from diseases such as Cystic Fibrosis, Huntington Disease, Alpha Thalassemia, Fragile X syndrome, and Muenke syndrome.

6. The National Institute of Neurological Disorders and Stroke (NINDS) Human Genetics DNA and Cell Line Repository focuses on the identification of new genes that causes or contributes to conditions such as Parkinson’s disease, Tourettes syndrome, epilepsy, motor neuron disease, and cerebrovascular disease.

7. The National Institute of Aging (NIA) Aging Cell Repository utilizes cellular and molecular research to determine the degenerative mechanisms and causes of aging. They have strict diagnostic criteria with cells collected over a span of thirty years. Scientists are using these cultures to study diseases such as Alzheimer’s disease, Parkinson’s disease, Progeria, and Werner Syndrome.

8. The National Human Genome Research Institute (NHGRI) Sample Repository for Human Genetic Research successfully completed the sequencing of the human genome. They now aim to participate in a variety of studies that focuses on the understanding of the structure and function of the genome and the role it plays in disease and health.

9. The National Eye Institute Age-Related Eye Disease Study (NEI-AREDS) Genetic Repository was founded to identify how macular degeneration and cataracts develop and progress. This is important as these two conditions are two main causes of vision loss among older patients.

Conclusion

Biorepositories are crucial in supporting different areas of research such as those focused on a specific diseases, broadly focused population studies, identification of genetic mutations, and many more. These studies may have a specific length and purpose and are ongoing studies that follow up with their participants for many years.

References:

1)      Biorepository. Wikipedia. Accessed 8/9/2018. https://en.wikipedia.org/wiki/Biorepository

2)      Greenberg B, Christian J, Henry LM, et al. Biorepositories: Addendum to Registries for Evaluating Patient Outcomes: A User’s Guide, Third Edition [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2018 Feb. Types and Uses of Biorepositories and Their Application to Registries. Accessed 8/9/2018. https://www.ncbi.nlm.nih.gov/books/NBK493635/

CRO Services

Introduction

A contract research organization or CRO refers to a company that provides support in the form of research. The research conducted through CRO services can be in one of the following fields:

• Biotechnology

• Pharmaceutical

• Medical device industry

In full a CRO is a company contracted by another organization to help lead and manage their trials, responsibilities, roles, and their function.

Services and Advantages

Some CRO services executed include such things as, but not limited to:

• Biologic assay development

• Biopharmaceutical development

• Commercialization

• Preclinical and clinical research

• Management of clinical trials

• Database design and building

• Data entry and validation

• Medicine and disease coding

• Quality and metric reporting

• Statistical

• Pharmacovigilance (the identification, detection, assessment, observation, and prevention of side effects of pharmaceutical products)

CROs are useful for companies when developing new drugs and medications as they reduce costs. CROs are able to simplify the development of new drugs and entry into drug markets. They also support governmental organizations, foundations, universities, and research institutions. CROs can range from small specialty groups to large international organizations. They aim to provide support for clinical studies and trials. Those that specialize in clinical trials services of a new drug are present from its conception until it is approved by the Food and Drug Administration (FDA) or by the  European Medicines Agency (EMA). Evidently CROs play a crucial role and pharmaceutical companies are continually outsourcing critical functions such as research and manufacturing to CROs.

The number of major corporations that are using CROs in clinical trials and the development of new drugs is increasing. Companies that establish contract with CROs aim to acquire the required expertise without having to hire permanent staff, keeping overhead low. Some CRO trade groups have claimed that contracting with CROs has helped reduce the cost by decreasing the time it takes to conduct a trial. This also means that the company that hires a CRO will not need the required infrastructure, manpower, and office space to conduct these trials. Some CROs can even manage all the aspects in a clinical trial starting from the site and patient selection all the way up until the final regulatory approval.

Regulatory Aspects

The International Council on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human use (ICH) defined CROs as “a person or organization contracted by the sponsor to perform trial-related duties and functions”. Their guidelines highlight the following:

• A sponsor can transfer all their duties and function to a CRO. However, the hiring company will be responsible for the integrity of data acquired from the CRO conducted study. It remains the hiring company’s responsibility to ensure that all the data is factual and backed by science.

• CROs should ensure quality control and quality assurance.

• All duties and functions transferred to a CRO should be in writing. The hiring company should oversee the duties and functions that are carried out on their behalf.

• Duties and functions that are not transferred to a CRO will remain with the sponsor.

Market Size and Growth

The Association of Clinical Research Organizations has estimated that more than half of clinical studies conducted by the pharmaceutical industry have been outsourced to CROs. The most popular field for CROs is therapeutic work including infectious disease, oncology, central nervous system, cardiovascular disease, and metabolic disorders. A further 27% work for within the biotechnology field while the remainder work for governments, foundations, and the medical device industry. The CRO sector is doing extremely well for an industry that just started a decade ago. There is increasing pressure facing medical devices organizations and pharmaceutical companies for the high cost of drugs and they are trying to lower costs without decreasing their profits. One of the best and most common solutions is to outsource clinical trial management as it results in significantly lower overhead costs.

By the year 2013, there were more than 1,100 CROs globally. However, there are many CROs that have gone out of business or that have been acquired. In 2008, it was estimated that the top 10 companies control 56% of the market. A 2007 estimate showed that the market would reach $24 billion in 2010 with a growth rate of 8.5% from 2009 to 2015. In 2016, the research and development spending increased by 15.5% from 2015 to 2020.

Conclusion

CROs are an effective solution as it provides an affordable option for companies to pursue the development and approval of new medication. Before the existence of CROs, this was a hugely expensive endeavor which was only embarked on when the likely hood of regulatory approval was high. With CROs, companies are now able to develop drugs for specific markets.

References:

1. Contract research organization. Wikipedia. Accessed 7/30/2018. https://en.wikipedia.org/wiki/Contract_research_organization

2. Stone K. Contract research organizations (CRO) definition. The Balance. Accessed 7/30/2018. https://www.thebalance.com/contract-research-organizations-cro-2663066