Antibiotic Resistance – It’s Complicated!

Big words, yes, but we can still figure this out. I’ve learned a lot about this topic as a patient advocate on antibacterial drug development committees with the Clinical Trials Transformation Initiative (CTTI) and the Brookings Institution. It’s really about the bug in the laboratory (lab), not in humans. That has to change if we want better solutions for patients.

First, Some Basics

Bacteria are small single cells whose whole purpose in life is to replicate.

http://www.biology4kids.com/files/micro_bacteria.html

Some bacteria are good. We’re only talking about the ones that infect people and make them sick. There are lots of words to describe different kinds of ‘bad’ bacteria – we’ll call them ‘bugs.’

Antibiotics: Drugs used to treat bacterial infections

Alexander Fleming discovered penicillin in 1928. Clinical trials, run by Edward Chain and Howard Florey, followed and they all shared the Nobel Prize in 1945 for antibiotics. More antibiotics are listed here. BTW, antibiotics are also called “antimicrobial” just to confuse things further.

cdc - plate testing Img26_sm

‘Superbug’ Hype Misses the Point

Have you heard about superbugs? They are definitely a problem. Some bugs resist some antibiotic drugs, due mostly to their overuse by doctors and hospitals (and in animals, but that’s another story). The situation, however, is not critical yet. This is not explained very well, nor is the fact that drug development must change if we are to have new drugs that truly work in people (also another story… soon, I promise!).

The resistance that doomsayers actually talk about pertains to resistant bugs in lab plates. This is different from what happens inside people.

“Disease is as much about the host as it is the infectious agent — the focus on microbes is hindering research into treatments, say Arturo Casadevall and Liise-anne Pirofski.”

Microbiology: Ditch the term pathogen – Nature.com Comment

Lab plates don’t have immune systems to protect them – people do. Infections also work differently in people who are otherwise healthy (they usually get better), compared to people who are sicker to begin with (this is where most problems occur).

In fact, the PATIENT matters MORE than the bug when you consider other important factors. For instance, Yaw et al wrote a paper which looked at death rates and hospital re-admissions from MRSA compared to Staph infections. They found similar results after matching factors like age, co-morbidities (other health conditions), the severity of illness, metastatic infections, and long-term care status.

Doctors & Hospitals Overuse

cdc - antibiotic prescription useDoctors commonly prescribe antibiotics “just in case” for patients before being diagnosed with a specific illness. This is called “empirical” practice and is not appropriate in many cases. This is especially true when there is no bacterial infection, or for diseases that resolve on their own. So patients get a general antibiotic first instead of getting what they actually need once they have a clear diagnosis. Research and medical systems have not focused on better diagnostics because they’ve been able to use antibiotics this way. Until recently…

What does Resistance Mean?

The system classifies bugs in labs as “susceptible,” “intermediate” or “resistant.” FDA sets criteria for these when it approves a drug label after reviewing patient outcomes from clinical trials.

The University of Pennsylvania explains the standards this way: “Note that this definition says nothing about the chances of clinical success; in fact predicting clinical outcome based on susceptibility testing and the use of drugs shown to be in the susceptible category is very imprecise. This imprecision is due to the effect of host responses, site of infection, toxin production by bacteria that is independent of antimicrobial susceptibility, the presence of biofilm, drug pharmacodynamics and other factors.”

Older Antibiotics Still Work!

cdc - antibiotic-resistance numbersResistant microbes or “pathogens” are commonly called superbugs now. Important point: antibiotics still work for most people in most situations, even when they have superbugs.

Resistance reflects how many drugs the bug can resist on a lab plate. It doesn’t show how many drugs still work for patients. Multi-Drug Resistance (MDR) means the bug is resistant to at least 3 drugs. This still leaves effective drugs that are available for patients, and most patients get better.

The fact is, only 1% (1 in 100) people die when they get a resistant bacterial infection. This is still too many, but compared to other diseases, this is an amazing success story. Patients who run out of antibiotic options are usually sick people whose immune systems don’t work well.

So, What is the Problem?

The Atlantic’s article called Antibiotic Resistance is Everyone’s Problem  summed it up nicely:

“You could get an infection that was drug-resistant even if you’d never taken antibiotics in the past.”

Ramanan Laxminarayan, Director, Center for Disease Dynamics, Economics and Policy

The more doctors prescribe antibiotics before knowing what disease to treat, the more superbugs are produced which affects everyone. This is especially true for patients who are sicker or have other illnesses. Doomsayers often hint at more “bloodstream infections” but when you look at the real numbers, there are more sick patients, not more resistant bugs.cdc - dr hospital solutions pdf_cover_as-factsheet

Another problem, as STAT News reports – people don’t understand when antibiotics should be used and when they shouldn’t. The World Health Organization (WHO) surveyed people in 14 countries, and found that 2 out of 3 are confused. “For example, 64% believe antibiotics can be used to treat colds and flu, despite the fact that antibiotics have no impact on viruses. Close to one-third (32%) of people surveyed believe they should stop taking antibiotics when they feel better, rather than completing the prescribed course of treatment.”

ALERT: These actions increase antibacterial resistance! Don’t do them!

The WHO Global Burden of Disease Project shows that deaths actually went down in all infectious diseases from 1990-2013. These real numbers sounds different from numbers that are often bandied about. Remember, there is a big difference between the absolute risk a person faces vs. the relative risk between rates or groups of people.

If You Missed Antibiotics Week, No Worries

Even though the WHO “World Antibiotic Awareness Week” and US “Get Smart About Antibiotics Week” (both Nov. 16-22nd) passed us by, we can use the tools all year, thanks to the Center for Disease Control and Prevention (CDC), WHO and the Food & Drug Administration (FDA). They track antibiotic usage and have tools for doctors, hospitals and states.

How YOU Can Help

cdc - 6 facts abt bacteriaThe CDC also has information for patients and the Public. Here are a few steps everyone can take:

  1. Learn which illnesses need antibiotics, and which ones don’t.
  2. Ask your doctor why they are prescribing antibiotics and if they are necessary for your illness.
  3. If you need antibiotics, take ALL of them. You don’t get personal resistance from antibiotics – you create resistant bugs if you don’t finish them as prescribed!
  4. Take this Antibiotics Quiz.
  5. Share this information with everyone you know.

All content © 2015 by Deborah Collyar unless otherwise specified. All rights reserved. Permission is granted to use short quotes provided a link back to this page and proper attribution is given to me as the original author.

Pain Meds – How NOT to Get Hooked

Any body can have pain that needs to be eased. Unfortunately, US healthcare has created an epidemic of addicts instead. It’s time to STOP this madness. Some are trying, but we all need to pitch in. Don’t think you need this? Think again!

  • In 2010, 1 out of 20 people over age 12 said they used a prescription painkiller for another reason. That’s 5% of our US population, people!
  • 7,000 people go to the emergency room EVERY DAY for this.
  • 44 people DIE every day from an overdose of pain meds.
  • You (or your family) can become addicted with ONE prescription.

Which Pain Meds?

Most of the problems come from a family of drugs called opioids. The most common opioids include: Hydrocodone (e.g., Vicodin), Oxycodone (e.g., OxyContin), Oxymorphone (e.g., Opana), codeine, and Methadone (especially when prescribed for pain). Addictions can also start from benzodiazepines that include Alprazolam (e.g., Xanax), Diazepam (e.g., Valium), and Lorazepam (e.g., Ativan).

Who is at risk?

In a word, everyone. Older people, patients with chronic diseases or cancers, adults of all kinds, and kids (even newborns). BTW, pain meds affect women differently than men. I found out how pervasive these problems are at a CTAF meeting on migraines (disclosure: I’m an Advisory Board member). Their report urges health systems and societies to educate patients and healthcare providers (medical staff), and CTAF created guides to help.

“…migraine patients in emergency departments (EDs)…receive opioids over 50% of theCDC women pain addiction
time, even though…strong evidence shows that opioids offer no short term benefits compared to other treatment options and raise the long-term risk of exacerbating migraines and of contributing to opioid dependence.”

CTAF 2014 Controversies in Migraine Management report

What YOU Can Do

CDC when prescription is problemIf you or your loved one take prescription painkillers, ask questions and talk with your doctor(s) and family. Questions like:

  • What is the goal of taking this prescription?
  • How long should I take these drugs?
  • Are there any risks to me from these pills?
  • What do I do with extra pills?

Learn how to:

  1. Manage pain.
  2. Know possible risk factors that can lead to overuse.
  3. Stop taking pain meds as soon as your pain gets better.
  4. Use the Food & Drug Administration (FDA) guide on how to get rid of unused prescriptions.
  5. If you have or suspect a problem, check the signs of pain meds abuse. Contact 1-800-662-HELP. If you have questions about specific medicines, call1-800-222-1222.
  6. The US National Institute on Drug Abuse (NIDA) also discusses drug addiction treatment.


CDC rx-painkillers-sales-and-deaths-700wIf you treat/care for patients
, PLEASE look at this CDC information (presentation and summary). Then LIMIT prescriptions and use lowest doses, TALK with patients about how to stop/store/dispose of pain meds, and AVOID combination prescriptions.

“Patients in pain need help, not addictions.” Deborah Collyar

If you can influence government/healthcare systems (i.e. everyone), help develop coherent state policies and Prescription Drug Monitoring Programs (PDMPs) that don’t discriminate against patients who really need pain meds. Research on pain meds is being done by NIDA and other sources. Other research articles in this area are available here. The US Center for Disease Control and Prevention (CDC) has been working on this since at least 2006.

Mathematics of Pain Relief

Mathematics of Pain Relief

“Reduce abuse and overdose of opioids and other controlled prescription drugs while ensuring patients with pain are safely and effectively treated.”

CDC 2012 Goal

You only have to hear one of the many heartbreaking stories to get the message. Please spread the word. We can all help solve this problem.

All content © 2015 by Deborah Collyar unless otherwise specified. All rights reserved. Permission is granted to use short quotes provided a link back to this page and proper attribution is given to me as the original author.

Informed about Changes to Research Consents?

Isolated patients need clearer informed consents to engage fully in research.

If not, you’ll be surprised soon. The Common Rule is changing – 1st time since 1991. The US NIH NINR says, “The Common Rule contains regulations that protect individuals who participate in research and is followed by 18 federal agencies.” Translation: these are the rules that apply to informed consent forms that patients sign to join research studies.

Your input (yes, you!) actually matters. Here is what you can do:

  1. Brush up on proposed changes: check out the summary, the full text in Federal Register, the public comments, and start thinking about yours as you read on.
  2. Comment by 1/6/2016 (was 12/7/15 originally) at the Notice of Proposed Rulemaking (NPRM). If you need the docket ID #, it’s HHS-OPHS-2015-0008.
    EDIT: the public comment period has been extended – post your comments before 1/6/2016.
  3. Be sure to remind them to STOP with this ‘research subject’ nonsense! People who join studies are trial participants, not subjects of some self-imposed royalty (or worse). And please ask them to require public study result summaries too.

If you want to post on your own, go for it. If you want to know my thoughts, read on…

“…bold moves to streamline the clinical trial process.”

Quorum Review IRB

Here is a quick summary of the proposed changes:

  • Tighter rules on explaining the study: shorter forms with key points highlighted for better patient understanding. Consent forms will become public. Hopefully, a step forward.
  • A written “broad” consent for all biological samples (e.g. leftover blood, surgery tissue) for any research, now or in the future. This includes samples that don’t have personal information attached, so each person won’t be identified.
  • Linking the level of risk with the type of Institutional Review Board (IRB) review.
    • Less risk = less review. A web-based decision tool will help figure this out.
  • More data security & privacy standards to protect trial participants’ confidentiality.
  • Requiring a single/central IRB for studies done at many sites.
  • Applying the Common Rule to all clinical trials in institutions that get federal funding.
  • Eliminate ongoing (continuing) reviews for some research.
Good review of Medical Ethics!

Good review of Medical Ethics!

For a quick refresher on ethical principles, please see the Belmont Report, and Medical Ethics for Dummies. It will make this much easier! This stuff matters – worth your effort.

So, what’s the big deal?

Many researchers think the new requirement of a written consent for all research samples will hinder medical advances. Until now, they collected samples from everyday medical care to use in research without each patient signing a form that says ‘yes, you can use my sample.’ Many of these samples had patient identifiers removed (called “de-identified” samples).

Translation: people working in the system chose which samples to take, and how use them. Some set up ethical methods, but patients weren’t involved in decisions (i.e., paternalistic).

Here are some arguments from the research perspective about changes (I’m paraphrasing):

  • This will negatively impact sample collections from the past (called “retrospective biobanks”). These samples are valuable because data (e.g., w/5 year follow-up) is useful now instead of waiting another 5 years if we start collecting now.
  • Changes only apply to physical samples, not data. Data also needs careful management to protect people from harm.
  • There is no oversight for the broad consent option, so how will we protect people from misuse? Issues like scarce samples, race and ethnicity, cultural norms, and harms to societal groups are not covered.
  • Changes create extra burden & cost on hospitals and clinics to use a broad consent form. Smaller places may opt out of research, which limits access to some communities.
  • Hesitancy to find patients for consent (or ask them about past samples), and the fear that many patients may not like being contacted.
  • Changes over-emphasize Autonomy (independent choice) vs. Beneficence (maximize benefit while doing no harm) and Justice (people affected should be offered access). See? I told you to check medical ethics first!

In a Perfect World…

This scenario may never happen since middlemen (like institutions) couldn’t make money off the data or samples, as many do now:

Patients would own their own samples, data AND electronic Medical Record (eMR/eHR). Healthcare professionals would interact with patients, but patients would be in total control of everything related to them. Flags in the record could be turned on for Y/N to donating research samples, data, etc.

BTW, how many current eMRs do you have? I’m up to 10 and many are wrong and/or incomplete!

My Take on NPRM Changes

I have worked directly with thousands of researchers for over 20 years, and I respect their dedication and efforts. Some have asked me if I can support their position on NPRM. After much contemplation, I have my own opinions regarding the proposed changes to the Common Rule (as usual). My current thoughts are:

  1. NPRM will change the way research samples are collected. It might reduce the number of samples that researchers have available if it is not explained well. That doesn’t mean, however, that people can’t decide for themselves.
  2. The arguments above represent a system averse to change, not on how to improve the research process and engage patients in new, open ways. Researchers are constrained by the old guard and fear extra burdens from the traditional research system.
  3. Modern social media and communication technologies can help find and engage patients. It takes new mindsets and methods, but old institutions don’t change easily. The NPRM should NOT be viewed in isolation, but rather WITH the rest of healthcare!
  4. Simple, direct plain-language consents can help people understand how samples have been used for years, and how they can continue to contribute to better care today. Some of us who create plain-language patient communications can help.
  5. New regulations (broad consent in this case) frequently allow for continuation (grandfathering) of older collections and procedures.
  6. NPRM must require specific oversight for the broad consent approval process. IRBs or usage committees should not be left out of this process, and a patient communication plan is CRITICAL.
  7. We should definitely include DATA (big, little & in-between) in the requirements. Data standards are desperately needed for research collections, which carry greater potential risk/harm than do body parts. Some groups are writing recommendation reports, but we need widespread action NOW.
  8. Extra burden? Every new initiative is an opportunity to make hospital procedures easier. Right now, patients give separate consents for any procedure they have done in a medical setting. While these are different from research informed consents, they are indistinguishable to most patients.

There are many more points, but I need to wrap up for now. Patients want to be more engaged, and this is an opportunity to better explain how the research community develops new treatments, procedures and tests that help people.

I frequently feel the need to remind ethicists not to “protect patients from themselves.” This is a step in the right direction (as long as they call us trial participants, of course!).

Involving those of us who represent patient voices in the implementation plans will help ensure that this works for patients AND those who serve them.

“…the ethical principle of respect for persons.”

NPRM 2015 Summary

All content © 2015 by Deborah Collyar unless otherwise specified. All rights reserved. Permission is granted to use short quotes provided a link back to this page and proper attribution is given to me as the original author.

Autumn Memories

My favorite season! Thanks to those who supported our fundraiser at the Alliance for Clinical Trials In Oncology Foundation. More hand-crafted jewelry pictures available here.

Autumn Leaves  Custom Name Sculpting  Moss Agate Earrings  Agate Wire Sculpture  Turquoise Memory Bracelet Crystal Ring  Pearl link lanyard

All content © 2015 by Deborah Collyar unless otherwise specified. All rights reserved. Permission is granted to use short quotes provided a link back to this page and proper attribution is given to me as the original author.