Pandemic Sparks Promising Future for Clinical Trial Speed and Flexibility
Like wartime medicine, the pandemic inspires and challenges medical innovation.
The silver lining of the pandemic is the reinvigorated sense of urgency breaking down
cumbersome and expensive barriers to the FDA’s phased approval process. While the research- lab-to-patient-arm trials for the highly successful COVID-19 vaccines famously moved the traditional pace to warp speed, other critical and life-altering medicines, devices and therapies also broke through during this period.
To be clear, the current surge of medical innovation through clinical trials in immunology, cardiology, multiple sclerosis, oncology and more, is not the result of a rush-to-market panic. All necessary and appropriate testing protocols to ensure quality are still being achieved, but at a more expedient pace in many cases. This is the good news.
“In times of crisis, we can accelerate the development and review process,” explains Andrew Badley, MD, infectious disease specialist, Mayo Clinic. “Throughout the pandemic, many of these steps were accelerated. No steps were skipped. It was just the amount of effort that went into the development and the review that was increased.”
Of course, there is also some not-so-good news about clinical trials today. During the pandemic, the number of new studies launched dropped by as much as 57 percent, according to Trials Journal, and the overall completion rate of clinical trials decreased between 13 and 23 percent globally. Shifting research priorities (11 percent of studies shifted to pandemic-related trials in 2020) and initial challenges in recruiting and following up with volunteer patients during the global lockdown contributed to this decrease. Often, a clinical trial is tethered to an academic medical center with participants centered in one geographical area, limiting volunteer pools and access.
However, the future speed and flexibility of clinical trial protocols is very promising, reflecting the long-term viability of alterations made to the fabric of patient care and research during the pandemic. Some of the new flexibility that is being assessed and considered for permanent use includes:
- Telemedicine. While telemedicine has been available for years, the lockdown most certainly fast-tracked adoption among researchers, regulators, physicians and patients. Clinical trial investigators can now use telemedicine for many patient check-ins, saving time and broadening the geography of volunteer pools. Dr. Ray Dorsey, a neurologist at the University of Rochester, noted in a recent article that his virtual clinical study of
genetic predisposition to Parkinson’s disease moved forward more quickly amid the pandemic, spurred by a rising number of online enrollments.
- Delivery. Like specialty pharmacies and physicians during lockdown, clinical trial investigators are now allowed to deliver trial medicine to volunteers.
- Remote Access. Volunteer participants are able to use online platforms for completing consent forms, and they can often visit their local physician for basic assessments. Some
trials also require less frequent check-ins, which can be important in recruiting volunteer patients. The growing number of smartphone-enabled applications that provide measurement of critical physiologic variables means patients don’t need to continually return to the hospital or clinic for tests during the trial. For instance, an entirely remote study testing vitamin D for treating COVID-19 and preventing transmission is being conducted by Brigham and Women’s Hospital; participants obtain their own blood samples with a finger prick, dot the blood drop onto filter paper supplied to them and mail it back.
The Clinical Trial Explainer
In the United States, the Food and Drug Administration (FDA) directs and approves all prescribed medicines, diets, diagnostics, devices and therapies. Clinical trials are the part of research that determines whether a medical intervention should be moved, or “translated,” from the lab to routine patient care. At each phase along the way, the team must answer different questions about safety, efficacy (whether the intervention works as intended) and whether there might be better options available. The current clinical trial journey to FDA approval, shown below, can take years, a mountain of paperwork and millions of dollars – there is room for improvement.
- Preclinical phase establishes the pharmacological profile and determines toxicity on at least two animal species.
- Phase I, a short study of 20 to 80 healthy people to determine safe treatment and dosing.
- Phase II, a larger-scale study of targeted patients to determine treatment effectiveness and identify side effects; can take months to years to complete.
- Phase III compares the trial intervention with existing therapies; requires several years of multiple data collection check-ins and comparisons. About 1 in 15 won’t make it past phase III.
- FDA Review and Approval
- Phase IV follows patients after therapy approval to ensure the intervention is working and prove the long-term benefits outweigh any risks or side effects.
Spurred by Alexander Fleming’s serendipitous discovery of penicillin in 1928, antibiotics have rightfully become wonder drugs, often able to change the course of deadly bacterial infections in a matter of days. But in recent years, their unmatched healing power has become overprescribed and over utilized, leading to concerning findings like these: Nearly 23% of antibiotic prescriptions filled in 2016 were unnecessary, and an additional 36% were prescribed for conditions for which an antibiotic is only sometimes recommended, according to a recent study from the Agency for Healthcare Research and Quality. Antibiotics awareness is good for your health
Unintended consequences far from benign
Patients may needlessly experience the drug’s side effects, such as rash, dizziness, nausea, diarrhea or Clostridium difficile infection (C. diff), which can cause severe diarrhea and may be life-threatening. On a larger, global scale, overuse leads to antibiotic-resistant bacteria, a growing danger that occurs when bacteria that have been exposed to an antibiotic mutate, rendering the drug ineffective against them. The Centers for Disease Control estimates that at least 2 million people are infected with antibiotic-resistant bacteria each year in the US, resulting in approximately 23,000 deaths. In fact, Fleming himself predicted the possibility in his 1945 Nobel Prize acceptance speech, saying: “It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them, and the same thing has occasionally happened in the body.”
Antibiotics: Handle With Care
That’s why the World Health Organization’s annual “Antibiotics: Handle With Care” campaign, launched in 2015, and the United States’ “Be Antibiotics Aware” program, launched the following year, are more important than ever in raising awareness as to why antibiotics aren’t always the answer. Becoming knowledgeable about the difference between bacterial and viral infections, and why an observational (“watch and wait”) approach to antibiotic treatment may be considered for conditions like sinusitis or ear infections, is critical to stemming the tide of overuse.
Below is a look at when antibiotics should be the treatment of choice, when they should be considered only after watching and waiting, or when they are not called for at all. Note that antibiotic drugs effectively kill bacteria but not viruses, which is why they are never recommended for viral infections such as colds or flu. However, not all bacterial infections require the use of antibiotics. As always, check-in with our office regarding what’s best for your individual health.
||ARE ANTIBIOTICS THE ANSWER?
|Common cold/upper respiratory infection
||No, primarily viral
||Cough expectorants sometimes combined with decongestants; antihistamines; and cough suppressants
||No, primarily viral
||Antiviral drugs by prescription
||No, primarily viral; thick, yellow or green mucus does not indicate bacterial infection
||Cough suppressants/expectorants; decongestants; antihistamines
||Only if diagnosed with group A streptococcal pharyngitis (the cause of just 5-10% of adult sore throats)
||Over-the-counter (OTC) pain relievers such as aspirin, ibuprofen and acetaminophen; throat lozenges
||Only if severe, or if symptoms persist after
10-14 days. Many studies show no difference in recovery rate with or without antibiotics.
Sinusitis infections are primarily viral; even if diagnosed as bacterial, a watch and wait approach may be recommended.
|OTC pain relievers
||Yes, if diagnosed as bacterial
||OTC fever reducers/pain relievers
|Middle ear infection
||For mild cases, watchful waiting or delayed antibiotic prescribing may be recommended
||Extra fluids; OTC pain relievers
|Cystitis, a common bladder infection in females
||Yes, this infection is usually bacterial
||Fluids; heating pad on lower abdomen; warm bath
||Yes, cause is a bacteria transmitted to humans by a bite from an infected tick; treatment with antibiotics in early stages of disease is most effective and prevents later-stage complications
Sources: Up to Date, CDC
About that penicillin allergy
Most people who believe they’re allergic to penicillin can take it without a problem, either because of the rash, they experienced as part of a virus or because the allergy resolved over time. You may want to get tested by an allergist to be certain, as research shows that patients identified as penicillin-allergic are more likely to receive very powerful antibiotics with greater side effects, and are also at higher risk of developing resistant infections that require longer stays in the hospital. It’s interesting to note that when skin tested, approximately 90% of people will test negative for a penicillin allergy.
Did You Know?
Reactions from antibiotics cause 1 out of 5 medication-related visits to the emergency department.
Source: Centers for Disease Control
The post Antibiotics Awareness is Good for Your Health appeared first on Specialdocs Consultants.
Managing Prescription Drugs: From Pickup to Take Back
If you are not taking your prescription medications as directed (or at all), you’re far from alone. Compliance is estimated at just 50% among U.S. patients. Unfortunately, adherence is a direct impact on quality and length of life, and overall healthcare costs, accounting for up to 50% of treatment failures and up to 25% of hospitalizations each year. The reasons for noncompliance vary, from patients not being convinced of the medication’s effectiveness, fear of side effects, the cost of certain medications to difficulty using tools (such as inhalers) or an aversion to injections. What can be done to manage prescription drugs more effectively?
For most, non-compliance is simply an unintentional consequence of forgetfulness or lack of organization. When faced with the need to keep track of a growing lineup of daily doses – and 77% of older adults manage two or more chronic conditions according to the National Council on Aging – it can become challenging to keep up. Fortunately, many solutions are available, from old school pen and paper to high-tech smartphone apps, that make it easy to reap the benefits of and manage your prescription medications.
- At the pharmacy, check your prescription instructions and make sure you fully understand dosage and timing; if best taken with food; interactions with other drugs, supplements, foods and alcohol; and side effects. If you have questions, ask the pharmacist or call our office.
- Tried and true, a pill organizer with compartments divided into sections for days of the week is most helpful in managing multiple medications. Keep the original bottles so you can quickly access any dosing and refill information printed on the bottle or packaging.
- Create a dosing schedule chart to keep next to the pill organizer, with a physical description or visual image of each pill. Use a spreadsheet or word processing program to make a list of all medications, times to take, and a check off space to indicate when taken. A number of pre-formatted charts are available online for download from the American Heart Association, the Food and Drug Administration and others.
- Online pharmacies are entering the mix, offering delivery of monthly medications sorted by dose.
Free smartphone apps can serve multiple functions. A few of the best:
- Medisafe medication management and pill reminder, highly rated by pharmacists for its comprehensiveness and usability, includes videos for many frequently used medications illustrating use, side effects, contraindications and other information, and emails you a history of your medications and doses in an Excel spreadsheet.
- Care Zone Health Information Organizer enables you to take pictures of your prescription and over-the-counter (OTC) drugs and supplements, populates with details, and sends reminders to take medications and refill prescriptions.
- Drugs.com also sends reminders, keeps your medication history, includes an interaction checker for other drugs and foods and provides access to updated information for more than 24,000 prescription and OTC drugs and supplements.
- Ask your pharmacist about preparing blister packs for daily or weekly medications; timer caps for pill bottles that beep to remind you when to take medications; gadgets that “talk” and relay the information verbally; and stand-alone electronic pill devices enabling easy input of medication name and measures, with an alarm that notifies you when the next dose is needed.
Properly Store your Prescription Drugs
- Pick a location that is up and away, like a kitchen cabinet (not the bathroom, unless it is well ventilated). Keep medications cool and dry and in a well-lit area to ensure you’ll reach for the right ones.
- Open the medicine bottle on a flat surface to prevent dropped pills from being lost down a drain or landing on the floor.
- Make a discard pile of medicines that are discolored, dried out, crumbling, leftover from a previous illness or past their expiration date—particularly biologic products, insulin, refrigerated liquids, eye drops, injectables or specially compounded medications.
Discard with care: Toss, flush or Take Back
Most prescription and OTC medicines can be thrown away in the household trash, with these important procedures:
- Do not crush tablets or capsules.
- Mix the medicines with kitty litter or used coffee grounds to prevent thievery or diversion of medicines from the trash. Then, place the mixture in a container such as a sealable plastic bag, and throw away.
- Remove the label and/or scratch off all personal information when disposing of a prescription vial.
- Check instructions included with prescription drugs such as narcotic pain relievers e.g. the fentanyl patch and other controlled substances, which must be flushed instead of discarded.
Even more convenient and environmentally sound are programs such as National Prescription Drug Take Back Day, sponsored by the U.S. Drug Enforcement Administration (DEA) in communities nationwide. The next one is scheduled for October 26, 2019: Find a collection site near you at https://takebackday.dea.gov, dispose of your unused or expired drugs safely and easily.
Did You Know?
Approximately 50% of medications for chronic disease are not taken as prescribed.
*Source: Annals of Internal Medicine
11.8 million pounds of prescription drugs collected since Take Back Day began in 2010.
*Source: Drug Enforcement Administration
The post Manage Prescription Drugs Effectively appeared first on Specialdocs Consultants.
Smoking Out the Myths: Medical Marijuana
Does medical marijuana offer a solution to treating epilepsy, chronic pain, anxiety and neurogenerative diseases? Or is it an untested, potentially unsafe treatment that will eventually turn out to be more of a pipe dream? As with so many of today’s biggest questions, the truth is somewhere in between. We bring you a down-to-earth view of this much-discussed and yet oft-misunderstood topic to separate the hype from the hope and dispel some Medical Marijuana Myths.
While the marijuana or hemp plant has been used for more than 3,000 years, research and treatment today is primarily focused on the extract known as CBD, a cannabinoid. Unlike one of the other chemicals in the plant, THC (tetrahydrocannabinol,) CBD has no psychogenic effects and does not produce the “high” commonly associated with marijuana. Hundreds of CBD-related tests are now in progress, and CBD products are available at dispensaries, online and are making their way into everything from coffee and yogurt to pet treats.
Last June, a major milestone was reached when the U.S. Food and Drug Administration (FDA) approved the CBD drug Epidiolex for two rare, severe forms of treatment-resistant epilepsy. Epidiolex, along with dronabinol and nabilone (which are synthetic cannabinoids previously approved to treat nausea from chemotherapy that has not responded to standard therapy), are now the only FDA-approved cannabis-based drugs.
The FDA was careful to note about Epidiolex: “This approval serves as a reminder that advancing sound development programs that properly evaluate active ingredients contained in marijuana can lead to important medical therapies. Controlled clinical trials testing the safety and efficacy of a drug, along with careful review through the FDA’s drug approval process, is the most appropriate way to bring marijuana-derived treatments to patients. Because of the adequate and well-controlled clinical studies that supported this approval, prescribers can have confidence in the drug’s uniform strength and consistent delivery.”
The FDA’s cautionary tone was necessary because of the many well-publicized clinical and preclinical trials underway to test marijuana and its extracts. Interest continues to grow, as evidenced by the numerous research projects in progress. The most prominent studies are focused on chronic pain, trying to evaluate whether marijuana is a safer and less addictive alternative to opioids.Other research is aimed at testing if cannabinoids improve the symptoms of multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, anxiety and insomnia, as well as its potential role in anti-inflammatoryand antiviral activity, blocking cell growth and preventing the growth of blood vessels that supply tumors.1
As promising as the research appears, it’s important to realize that at this time, not enough large, clinical trials have been conducted to show that the benefits of marijuana outweigh the potential risks. Research is still preliminary and much remains unknown about CBD and other cannabinoids’ optimal dosing range and the best route of administration (by mouth, inhaled, topically or sprayed under the tongue). Importantly, because they are not FDA-approved, the levels of THC or CBD can differ greatly from one dispensary to another or one batch to another.
Side effects are also hard to predict because potential impurities and variations in dosage are not addressed as they are in all FDA-regulated products. We are only starting to evaluate side effects which may range from minor dry mouth and dizziness, to death. It is also unclear if the products interact with other medications. An added concern is that older and sicker people may be more vulnerable to the drug’s side effects.
Our bottom line: although CBD is readily obtainable in most parts of the United States, and laws legalizing its use for medicinal purposes continue to pass, we need to take a step back and realize the process is far from complete. The fact is the scientific evidence does not yet support many of the claims to ease symptoms of certain diseases, improve quality of life and relieve pain, nor has it been approved for use as a cancer treatment. As Cleveland Clinic’s head of Employee Health Services recently pointed out, medical marijuana has not yet undergone extensive clinical trials, public hearings and approval by the FDA, or been thoroughly tested for safety and efficacy. His recommendation is one we can all support – focus on research that isolates specific compounds found in marijuana, produces a dose-specific medication, and submit it to testing and regulatory processes.
1 National Cancer Institute, 2019
Did You Know?
Number of cannabinoid research projects supported by the National Institutes of Health in 2017
Number of states (including the District of Columbia) that have approved the medical use of cannabis as of 2018
The post Medical Marijuana Myths appeared first on Specialdocs Consultants.
The New Approach to Pain Management: Fewer Pills, Lower Doses, More Vigilance
It’s hard to imagine a medical crisis more widely discussed, dissected and debated in the last two years than opioid abuse. As a result, clear action steps have been taken, including retooling of the 2016 guidelines for opioid-prescribing protocols – dosage recommendations, follow up assessments and ongoing monitoring were reconsidered and adjusted. In short, for patients with chronic pain not from cancer, non-pharmacological treatment and non-opioid medications should be evaluated first, and opioids used for pain management only when:
- other alternative therapies have not provided sufficient relief, and
- pain is adversely affecting a patient’s function and/or quality of life, and
- potential benefits of opioid therapy outweigh
Following are details on the newest developments, and how they may impact the way you’re treated for pain, from hospital bed to physician office.
Minimize and customize dosage. Not surprisingly, the dosage recommendations for exercising caution are lower than in earlier guidelines, beginning with even relatively low doses (20-50 morphine milligram equivalents (MME) per day). The lowest effective dose, for the shortest period needed, will be used to treat acute pain. In most cases, even pain following surgery does not require opioids for more than three days. Several high-profile institutions have changed their opioid prescribing guidelines following surgery.
At Johns Hopkins, a panel of health care providers developed recommendations for the number of five-milligram oxycodone pills needed after almost two dozen common procedures, finding that some required none, while the maximum of 20 pills was appropriate for others. The prescribing limits were designed to help prevent patients from receiving unnecessary opioid pills after surgery and ultimately face a one-in-16 risk of becoming a long-term user.
“Prescriptions for pain meds after surgery should be custom tailored to the operation and a patient’s needs and goals, but the hope is that these guidelines will help reset ‘defaults’ that have been dangerously high for too long,” the study’s author reported in a recent Journal of the American College of Surgeons.
An open discussion. It is now acknowledged that opioids present a risk to all patients, and risks must be clearly presented when starting therapy. These range from common (constipation, nausea) to serious (respiratory problems, opioid use disorder, overdose).
Establish realistic treatment goals. It’s essential to realize there’s no cure for chronic pain, but work toward pain relief to improve function and quality of life. “SMART” goals – specific, measurable, attainable, relevant and time-limited – should be set at the start to determine end points and be continually reassessed.
Continual monitoring. Opioids should only be continued after confirming that clinically meaningful improvements in pain and function were realized without significant risks or harm. In regular checks, patients will be asked to rank their pain, and level of interference with their enjoyment of life and general activity. A 30 percent improvement from baseline scores would be needed to continue the therapy. Reassessments are recommended within a few weeks after starting, and at least every three months throughout the course of treatment.
Not recommended for elderly patients. A body of evidence shows possible harm from long-term opioid use in older patients, who metabolize medications more slowly and so may be prone to side effects such as respiratory and cognitive impairment. UCLA Comprehensive Pain Center experts advise a multidisciplinary approach using psychological support, physical therapy and other complementary therapies.
Proper disposal of unused opioids. Noting that a large part of the opioid abuse crisis was spurred by people taking medications not prescribed to them, new guidelines emphasize not leaving unused pills in the medicine cabinet “just in case.” Patients are advised to dispose of them as quickly and appropriately as possible.
New approaches to addiction. According to a recent editorial in Mayo Clinic Proceedings, looking beyond the “supply side” issue to target the “demand” side of opioid use is critical to addressing why patients were initially drawn to using opioids. The authors recommend screening for depression and other psychiatric disorders which are often the impetus for patients to over-use opioids. Other studies posit that as many as 65 percent of overdoses reported at poison control centers were actually suicide attempts, underscoring the need for comprehensive psychological evaluation and treatment.
Optimize use of non-opioid therapies. A growing list of options includes:
- Acetaminophen (Tylenol®) or ibuprofen (Advil®)
- Muscle relaxants
- Cognitive behavioral therapy – a psychological, goal-directed approach in which patients learn how to modify physical, behavioral, and emotional triggers of pain and stress
- Exercise therapy, including physical therapy
- Medications for depression or seizures
- Interventional therapies (injections)
- Exercise and weight loss
- Alternative therapies such as acupuncture
Fast Facts; Did You Know?
70–80% – 70-80% Percentage of opioid pills prescribed for pain management after surgery not used by patients
Source: Johns Hopkins
The post Pain Management: The New Approach appeared first on Specialdocs Consultants.
Nothing erodes the quality of life faster than pain and unfortunately more than half of American adults report they live with it on a chronic, recurring basis. That makes it easy to understand why, when seemingly safe, effective opioid drugs became widely available in the 1990s, they were quickly embraced by physicians and patients. Considered one of the most promising developments in pain management in decades, opioids such as oxycodone (OxyContin, for example), hydrocodone (Vicodin) or meperidine (Demerol) had already proved highly effective on a short-term basis to treat acute pain. The mechanisms were clear: opioid molecules travel through the bloodstream into the brain, attach to receptors on the surface of certain brain cells and trigger the release of dopamine in the brain’s reward and pleasure center.
However, what was not known was how patients reacted to these medications when taken daily for weeks, months and years to treat chronic conditions ranging from headaches and stubborn lower back pain to neuropathy, fibromyalgia and severe degenerative joint disease. As use of opioids for chronic pain (defined as lasting longer than three months) became widespread, reports of unwanted side effects emerged, along with doubts about long-term efficacy and optimal outcomes. Most alarmingly, the potential for abuse and addiction materialized into a full-blown crisis, evidenced by stark statistics like these:
- Opioid prescriptions increased 7.3% from 2007-2012; by 2013, 1.9 million people were reported to be abusing or dependent on opioids. As many as 25% of people prescribed opioids on a long-term basis struggle with addiction.
- 165,000 Americans died from overdosing on prescription opioids from 1999-2014, climbing from 3 deaths per 100,000 people to 9; the highest rates were seen among 25 to 54-year-old white Americans.
Clearly, sweeping changes were needed, and in response, new recommended guidelines for safer pain management were issued by the Centers for Disease Control (CDC) last spring, and received
strong endorsement from well-respected organizations including the American Academy of Pain Medicine and the American College of Physicians (ACP). According to ACP, the recommendations are “reasonable, based on the best available evidence, and find the right balance between educating about the hazards of opioids while recognizing special circumstances where such medications may be an important part of a treatment plan.” The recommendations specify best practices for dosage levels and usage, and raise awareness of the risks posed to all patients by the drugs. Please note that these are recommendations only and may be altered at the discretion of the physician treating you to fit your unique needs. These include:
- Non-pharmacologic and non-opioid therapy are preferred for chronic pain. Opioid therapy should be used only if expected benefits for both pain and function are anticipated to outweigh risks.
- If opioids are used, they should be combined with non-pharmacologic and non-opioid pharmacologic therapy, as appropriate.
- Physicians should establish treatment goals with their patients before starting opioid therapy, including realistic and clinically meaningful goals for pain and function, and an ‘exit strategy’
should the therapy need to be discontinued.
- Use immediate-release opioids instead of extended-release/long-acting opioids.
- Use the lowest effective dosage, and carefully reassess individual risks and benefits when increasing dosage to ≥50 morphine milligram equivalents per day.
- Prescribe immediate-release opioids for acute pain in no greater quantity than needed for the expected duration of pain – three days or less will often be sufficient, more than seven days will
rarely be needed.
- A frank physician-patient discussion regarding the risks and benefits of opioids should take place before starting therapy. An evaluation of benefits and harms should be scheduled within one to four weeks of starting opioid therapy, and repeated at least every three months. If benefits do not outweigh harms of continued therapy, physicians should explore alternatives (see sidebar) with patients and work with them to gradually taper off to lower doses and ultimately discontinue use.
The post The Painful New Reality of Opioid Prescriptions appeared first on Specialdocs Consultants.