The physiology and behavior of children makes them more susceptible to the adverse effects of a variety of toxins. In decades past, most issues related to environmental exposure amongst children focused primarily on lead poisoning and second-hand smoke. Off late, the focus has shifted to health effects of other types of exposures as well, for instance, chemical irritants and allergens (eg. formaldehyde resins), pesticides, and other toxins including indoor and outdoor air pollutants. The pediatric history covers a variety of screening questions that are asked during the first as well as follow-up visits, as relevant to the development stage of a child. Questions focus on finding the type of home and surrounding environment most frequented by the child as well as the occupation of the parents.

Work and environmental exposures can lead to or worsen several different types of common diseases, for instance asthma, dermatitis, hepatitis B, carpal tunnel syndrome, and cancer. In a number of cases, the environment or work-related illnesses do not show distinctive clinical presentations: asthma resulting from a cat allergy does not differ from asthma caused by latex allergy; median nerve entrapment associated with repetitive motions has the same set of signs and symptoms as carpal tunnel syndrome arising due to pregnancy; headache caused by inhalation of carbon monoxide can be diagnosed as severe headache or migraine. Symptoms associated with hazardous exposures can be similar to normal complaints involving any body system and other common medical diseases. There are certain exposures that can lead to immediate or subacute symptoms (for instance acute chemical reaction and allergic reactions), whereas others can result in more delayed outcomes (for example pneumoconiosis and cancer). The differentiating feature is the association to an occupational or environmental exposure. The history of occupational and environmental exposures can play a significant role in the identification, treatment, and prevention of occupational/environmental injuries and illnesses.

It is difficult to measure the magnitude of occupational illnesses and injuries. The United States Bureau of Labor Statistics (BLS) that provides statistics based on surveys of private companies having more than 11 employees (an underestimate of the real totals), reported 5,488 fatal accidents related to work (3.7 for every 100,000) and around 4.0 million nonfatal illnesses or injuries (4.2 for every 100 equivalent full-time workers in 2007). Approximately 2.1 million illnesses and injuries necessitated recuperation away from workplace, restricted duties at work, or job transfer.

Examination of data gathered from a number of data sets (including the BLS) to generate the following approximation of the total number of occupational illness and injury occurring annually in the United States: 6500 fatalities from job-related injuries; 13.2 million nonfatal injuries; 60,300 deaths resulting from job-related disease; and 862,200 illnesses (work-related). The entire costs involved were approximately $171 billion. It was noticed in a study of health maintenance organization (HMO) members diagnosed with adult-onset asthma that 21 percent of cases were associated with occupational exposure.

Epidemiological studies involving firefighters and first responders are worth noting. For instance, the World Trade Center (WTC) disaster in the United States in September 2001 created controversy over conditions associated with exposure to toxic gases and dusts. Studies involving first responders within the first month after the WTC disaster revealed that bronchial reactivity was three times more in case of individuals who were at the site in the morning when the disaster occurred, in comparison to those who came later. Studies in the following year that focused on pulmonary function of rescue workers belonging to the NYC Fire Department showed significant reduction in average FEV1 in comparison to pulmonary function studies that were undertaken five years earlier. It has been reported that the incidence of “sarcoid-like” granulomatous pulmonary disease has increased. Also, an increased occurrence of fatal coronary heart disease has been noticed while comparing firefighters who were assigned emergency firefighting duties with those who were not assigned urgent duties.

Off-label use

An FDA approval implies that the drug can now be used to treat a specific condition when it is administered in the manner described on the drug’s label. Further clinical research may be required to study other potential uses of the drug, for example, to treat a different form of cancer. An off-label use of the drug is said to have occurred when an FDA-approved drug is prescribed by a doctor to treat conditions that are not mentioned on the label or in a manner that is not described on the label. There are many reasons as to why it is a common practice to use off-label drugs to treat cancer. Firstly, drugs are usually approved for the treatment of a specific form or stage of cancer. Once approved, a drug that effectively treats a specific form of cancer is often identified as an effective treatment for other types of cancer as well. Secondly, there are certain cancers that necessitate the use of multiple drugs. In that case, one or more drugs are often used off label. Treatment regimens involving multiple drugs are also evolving constantly, as doctors evaluate new drug combinations to improve the quality of patient care.

Getting FDA approval for new labeling information

In order to get FDA approval for new labeling information meant for an existing drug (FDA approved), the drug sponsor should file a supplemental marketing application with the FDA. This is done to ensure the drug’s safety and effectiveness, as relevant to the new labeling information. In certain cases, the sponsor may find out that the information required to file a supplemental application is not as extensive as may be necessary for initial approval. The FDA has launched a variety of initiatives to encourage supplemental applications involving products used in the treatment of cancer. For instance, the FDA constantly interacts with academic, private and professional groups engaged in cancer-related research and treatment. After obtaining their views about off-label drug, the FDA then contacts drug sponsors to assist in the supplemental application submission process.

Orphan drugs

Drugs that are used to treat rare diseases affecting less than 200,000 Americans are referred to as orphan drugs. Since only a small number of patients need these drugs, it may not be possible for the drug’s sponsor to recover the drug development costs. Under the Orphan Drug Act, sponsors are given incentives to develop new drugs for the treatment of rare conditions, including several different types of cancer.

Making the drugs available to patients

Drugs that are being studied and have yet to receive FDA approval are called investigational drugs. Access to these drugs is available only to patients who have enrolled for clinical trials. The drug may receive FDA approval after the end of the clinical trial if there is evidence to prove that benefits of the drug outweigh its potential risks. Based on the awareness that patients, after having tried all available treatment options, may be willing to try new treatments with higher risks, the FDA has initiated the following three programs to ensure that patients with serious illnesses such as cancer can have access to investigational drugs.

Special exception/compassionate exemption: Although enrolling in a clinical trial is the best way to access investigational drugs, these trials often have eligibility criteria (strict rules) to determine if they will be appropriate for a patient. In case the trial is considered inappropriate for a patient, a special exception/compassionate exemption can be used to provide that patient with access to the investigational drug. An exception request should be submitted to the FDA jointly by the patient’s doctor and the sponsor of the drug. The FDA reviews every application on a standalone basis.

Treatment INDs: The treatment Investigational New Drug (treatment IND) program run by FDA allows drug sponsors to request that access to an investigational drug be provided to patients who are not considered appropriate for clinical trials or those for whom no other suitable treatment option may be available. There should be sufficient evidence to prove the drug’s effectiveness and also that it does not have unreasonable risks.

Group C drugs: An agreement between the National Cancer Institute (NCI) and the FDA, the Group C program seeks to provide oncologists with investigational drugs that normally are available via participation in an NCI protocol. Usually these drugs are in their phase III trials and there is evidence to prove their effectiveness in relation to a specific type of tumor. Using this route and after obtaining informed consent, patients who may not have participated in clinical trials can still have access to and benefit from a potentially effective treatment.

Patient can contribute to the drug development and approval process by enrolling themselves in clinical trials. Participating in clinical trials not only contributes to improvements in cancer research and treatment but also allows enrolled patients access to closely monitored care and regular reviews on the status of their disease. The FDA has launched two programs to seek patients’ involvement in the drug development and approval process.

FDA’s Cancer Drug Development Patient Consultant Program seeks to include the views of patient advocates, as relevant to the drug development process. In meetings (via phone), selected patient advocates interact with the FDA and drug companies and carry out discussions on the different areas of the drug development process.

The Patient Representative Program provides cancer patients with the option to participate as a patient representative in the advisory committee meetings. A patient representative is expected to provide insight on problems, issues and /or questions, as considered important and relevant to the patient and their family members. A patient representative is required to meet several different qualifications, and those designated as voting members should be assigned the status of special government employees.

1) Accelerated approval

The accelerated approval program run by FDA allows sponsors to request approval on the basis of alternate findings. Also called surrogate endpoints, these are indirect assessments of disease status, for example, a change in lab results or improvements in symptoms related to the disease. These endpoints can also be used to assess the effectiveness of the treatment or therapy. With accelerated approval programs, the approval process for drugs meant for life-threatening diseases can be expedited in order to provide for an unmet medical need.

2) Engaging drug sponsors early in the drug development process

By interacting with drug sponsors in the early stages of the drug development process, the FDA is trying to reduce the time spent on the development of new drugs. With this effort, the FDA seeks to speed up the development, review and marketing of new treatment options. The FDA conducts meetings with the drug sponsor on a regular basis in order to ensure that an agreement is reached on the ideal design of clinical research and the resulting data is reviewed in a timely manner.

Way back in the 1920s, a German scientist by the name of Otto Warburg reported to the world that cancer cells metabolize sugars in different ways than normal healthy cells. While such a discovery may not seem particularly momentous, this near century-old discovery is continuing to prove its importance by opening the door to a wide number of potentially effective new cancer therapies.

Warburg’s discovery has already resulted in dramatic cancer treatment breakthroughs – modern-day PET-CT scans help pinpoint tumors by highlighting locations in the body that are high in metabolic activity. Now, scientists are once again revisiting the topic of cancer cell metabolism as they search for new ways to not only diagnose the disease, but fight it as well.

As a recent Harvard Medical School study suggests, a cancer cell’s ability to maximize sugar metabolism is likely a critical factor in the disease’s ability to rapidly divide and spread throughout the body. Indeed, the Harvard study concluded that cancer cells use less chemical energy during cell division, and still manage to over-produce resources necessary for new cell growth.

Similar studies have suggested that augmentation to a healthy cell’s metabolism function is critical for cell mutations.

As a result of cancer’s strong ties to sugar metabolism, researchers are hopeful that starving cancer cells of important enzymes that are necessary for processing sugar can shut off cancer growth.

While the line of research is still in its infancy, a groundswell of support is currently in the works. Recently, Agios Pharmaceuticals raised $33 million for the specific purpose of studying metabolic functions. Additionally, the American Association for Cancer Research recently held a 4-day meeting devoted entirely to the topic.

Cancer metabolism is seen as a promising path due to its wide-sweeping occurrence. As it turns out, there are very few commonalities shared between different types of cancers that can be effectively targeted for broad treatment purposes. However, it appears that sugar metabolism is a key component of cancer growth among the majority of cancer types.

While it is still too soon, and perhaps overly optimistic, to suggest that disrupting cancer metabolism may be the breakthrough necessary for curing cancer, the field remains promising. Agios has already identified an enzyme that is necessary for cancer metabolic functions. Presently, they are working to develop a drug that blocks this enzyme without harming normal cell production.

Resource:

http://www.boston.com/business/healthcare/articles/2009/12/21/old_discovery_could_bring_new_cancer_therapies/

With its fast track drug development programs, the FDA seeks to facilitate the development of new drugs and speed up their approval process. This is especially true in case of drugs that can provide for unmet medical needs pertaining to debilitating or life-threatening diseases such as cancer. An unmet medical need is said to exist when no standard treatment is available for a specific disease or condition or when the existing treatment is not effective. Based on these factors, drug sponsors may request the FDA to assign the fast track designation to the new drug. If approved, the drug may come under the purview of a fast track program, which can speed up the approval process.

The drug regulatory agency in every country has its own specific requirements for drug approval. A drug that has received approval in Japan or Europe cannot be sold in the U.S. market until it gets approved by the Food and Drug Administration. The creation of the International Conference on Harmonization (ICH) was part of the cooperative effort between the drug regulatory agencies of U.S., Japan, and Europe. The primary objective of ICH is to ensure that information required for making decision related to drug approval are similar between different countries. With ICH, drug sponsors who may have received approval for a drug in Japan or Europe can file the same research papers with the FDA. They may not have to conduct additional research to get approval for the general use of the drug in the United States.