FDA Mulling Trial Design Issues for Long-Term Opioids in Chronic Pain

Posted on May 12, 2023 by Pharmaciststeve

The perceived prevalence of OIH in clinical practice is a relatively rare phenomenon

Opioid Induced Hyperalgesia—Exploring Myth and Reality

FDA Mulling Trial Design Issues for Long-Term Opioids in Chronic Pain

https://www.medpagetoday.com/painmanagement/opioids/104064

To evaluate the long-term efficacy and tolerability of a representative extended-release (ER)/long-acting (LA) opioid in a 12-month placebo-controlled trial, FDA staff are considering an enriched enrollment randomized withdrawal (EERW) study design, they noted in a briefing documentopens in a new tab or window ahead of an advisory committee meeting.

On Wednesdayopens in a new tab or window, the Anesthetic and Analgesic Drug Products Advisory Committee will consider the advantages and limitations of using an EERW design to evaluate morphine sulfate ER in a phase IV trial — part of a postmarketing requirement — among patients with chronic non-cancer pain who had initial tolerability to the ER opioid.

The committee will also discuss looking at the incidence of opioid-induced hyperalgesia (OIH), a condition in which a patient’s increase in pain can be attributed to the treatment with an opioid, among other objectives, such as changes in physical function and in levels of anxiety and depression.

FDA staff said the EERW study protocol might be the best available design amid the many challenges of conducting placebo-controlled clinical trials for chronic pain over an extended time period.

“Due to the unique clinical considerations regarding patients with chronic pain appropriate for long-term opioid therapy, the design of the clinical trials intended to evaluate the treatment effect of analgesics in this patient population poses certain challenges,” they wrote. “There are different options with respect to clinical trial designs, each with their own advantages and disadvantages.”

“There are also challenges in selecting appropriate patients, controls, and endpoints, as well as to retain enough patients to generate interpretable data,” they added.

To address these concerns, FDA staff wrote that the EERW design “varies from the conventional clinical trial design in the timing of randomization and dichotomization to two treatment groups, opioid or placebo,” noting that this design uses “a long prerandomization period and a relatively short period where patients will be on double-blind drug.”

“The EERW design, while not ideal, appears to offer the best compromise to answer this public health question,” they wrote.

In addition, the EERW study design “may inform the incidence of OIH provided that the protocol includes appropriate OIH surveillance and a prospective definition of OIH,” they added.

The advisory committee will also be asked to discuss the likelihood of maintaining a sufficient number of study participants using the study design, specifically considering the acceptable degree of dropout related to its effects on the interpretation of outcomes.

FDA staff noted that dropout during a 12-month trial could be the most challenging aspect of evaluating the long-term efficacy of opioids. “Our prior experience suggests a substantial dropout rate even over the 12 weeks of prior randomized trials (in the 40-50% range), and therefore raises the real concern that a dropout rate in a 52-week duration trial would be higher, undermining the robustness of the between-group comparison at the trial primary timepoint,” they wrote.

Other factors, such as the adequacy of the length of the study (38 to 52 weeks) and secondary endpoints, including time-to-treatment failure, pain scores, and a proposed tapering scheme to mitigate concerns over unblinding the participants, will also be discussed.

Finally, the advisory committee will be asked to consider other potential study designs that could be used in the assessment of long-term use of opioids.

“With respect to the parallel-group, placebo-controlled randomized controlled study, this approach poses the challenges of recruiting patients into a long duration placebo-controlled study — in patients who have severe pain intensity having failed other treatments,” FDA staff wrote. “The prior study included a long-term placebo-controlled period and failed due to recruitment issues.”

After the original postmarketing requirement was issued in 2013, the Opioid Postmarketing Requirements Consortium (OPC) started a 26-week study in patients with high opioid requirements in 2016, but decided to end the study in 2018 due to several factors, including challenges with patients and changes to opioid prescribing requirements. The OPC submitted an updated protocol for a 52-week trial in January 2020. With guidance from FDA staff, the EERW protocol was refined and submitted for consideration.

Last week, the FDA issued several updatesopens in a new tab or window to the prescribing information and labeling for immediate-release (IR) and ER/LA opioids that will make the increased risk of overdose with increased doses more clear. The changes will also highlight the risk of OIH.

While the FDA typically follows the advice of its advisory committees, isn’t required to do so.

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25 Ways Generative AI Will Change Healthcare

Posted on May 12, 2023 by Pharmaciststeve

I find this interesting, especially #6,7 & 9. Could something like this, generate specific treatment plans for chronic pain pt who have had their pain meds decreased or cut and BP increases and 4 or 5 different BP meds and their BP doesn’t change. Would the AI be smart enough, to realize the cause & effect of increased BP and the reduction of pain management and recommend that pain meds be restarted and recommend increased pain meds dose if the BP goes down some, but not down to expected BP range.

For those of you who watch the TV show Chicago Med, what they call OR 2.0 seems to have wall to wall large video screens and cameras and a AI interactive voice that monitors just about everything that goes on… including comparing the surgeon’s activity/movement as compare to their previous surgeries and have called out a surgeon that was not up to his “normal movement/proficiencies.

Of course, these AI program can be designed with biases, like prohibited from recommending the implementation or increasing opioids or control meds.

25 Ways Generative AI Will Change Healthcare

https://shulkinblog.com/f/twenty-ways-generative-ai-will-change-healthcare

It seems Generative AI (GA) is all that everyone is talking about. Some futurists are predicting major changes to the way we live our lives and others even suggest that we are facing an existential risk to mankind. The truth is that we are clearly in unchartered territory and none of us really know where this is going to lead.

There is no doubt that GA will be disruptive to healthcare’s status quo. As GA grows in sophistication, it will change or even eliminate many traditional healthcare roles. GA will also raise new concerns about ownership and privacy of patient data. And no doubt there will be other unintended consequences that arise from this technology. But the potential for improving care and outcomes is probably the most exciting to think about.

Rather than looking too far into my crystal ball, I’ve chosen to look at the most likely places we will see5 the impact of GA in healthcare. GA is already being used in a number of the areas that I have listed below. Where possible, I’ve identified companies that are already demonstrating results from their work.

1. Medical Imaging and Pathology – Generative AI will help will soon become standard of care in radiology and pathology to ensure more accurate diagnosis, improve the efficiency of processing and reading studies, and address workforce shortages. (Ibex is a company using AI to improve diagnostic accuracy in pathology readings)2.

2. Patient Empowerment and Navigation- GA will dramatically improve the ability of patients to get information about their health and treatment options. This will fundamentally change the nature of the patient-provider relationship GA will enable chatbots to create personalized medical advise and assistance for patients and enable more efficient navigation of the health system.(Galileo is allowing patients to connect with the right healthcare solution)

3. Remote Patient Monitoring- GA will increasingly be used to alert medical professionals to trends seen in vital signs, physiologic and patient reported data that can predict patient risk. It will also allow monitoring to become more autonomous independent of healthcare professionals. (Cadence is providing remote monitoring solutions and data analysis for several conditions like congestive heart failure and Kaia is providing analysis of data from musculoskeletal conditions)

4. Improved Diagnosis- GA will be used to analyze patient data (electronic patient records, laboratory test results, radiographic images, genomic data) to improve diagnostic accuracy.(Google Health/Deep Mind and Babylon Health are using machine learning to better match symptoms with diagnoses).

5. Drug Discovery- GA will help identify new drug candidates faster and cheaper than current methods (Saama is a company that is ingesting data and GA to dramatically improve the time required for drug discovering)

6. Personalized Treatment Plans- GA will generate specific treatment plans for patients based on medical history, lab data, and genetic makeup.

7. Reduce Drug Adverse Events- GA will be used to identify side effects and pharmacogenomic difference for patients taking multiple medications, OTC products, dietary supplements, and foods.

8. Fraud, Waste, and Abuse- GA will help detect fraud and inappropriate utilization through pattern recognition and data identification.

9 Health Risk Assessments- GA will be used to increasingly predict a patients risk of developing disease and help target preventative care and vaccine applicability.

10. Access to Care- GA will be used to help match supply and demand of healthcare services, address no-show rates, and better predict resource utilization in order to ensure more efficient and timely scheduling of services. (Dexcare is a company using technology to address access)

11. Reduced Documentation- GA will be able to create patient notes and complete other paperwork tasks that take time away from patient time with healthcare professionals. This will improve efficiency, the patient experience, and reduce professional burnout.

12. Virtual Assistants and Robotics- GA can create automated processes and robotic devices to speed workflow in clinical settings. These virtual assistants and new robotic innovations will make medical practices more efficient and help in a variety of ways including logistics and supply chain management. Robotic patient assistants will become commonplace in long term care and the home settings for assistive care services.

13. Regulatory Compliance- GA will enable simulation techniques and synthetic data to test new pharmaceuticals, devices, and digital strategies to examine real world evidence, speed regulatory approvals, and to ensure adequate post-marketing surveillance.

14. Pre-Authorization of Services- GA can efficiently run data from patient reported data, physician records, and other clinical sources to ensure compliance with guidelines and give rapid authorization to high costs services and products.

15. Medical Education and Simulation- GA be increasingly be used to train medical professionals, assess competencies, and test new devices and procedures to improve safety ensure faster regulatory approval (Companies like Indegene and Edocate are increasingly using interactive data and scientific information to provide interactive education)

16. Medical Billing – GA will help with revenue cycle management by improving the accuracy of billing, coding records, finding data from various clinical sources for accurate risk adjustments, and in ensuring accurate revenue capture. (Cedar is using data with behavioral economics to improve transparency and the billing experience).

17. Clinical Trial Design- GA can run various scenarios and use synthetic data to test and identify clinical trial designs with high precision for recruitment, data analysis, and compliance with protocols.(Trinetx is a company that is using patient data to develop better clinical trials and drug discovery and MD Clone is creating synthetic data sets to better test innovation and new discoveries}

18. Surgical Performance- using video capture of surgical procedures, GA can identify unnecessary variations in surgical performance, identify preventable postoperative complications and improve surgical operating times by predicting surgical resource needs. (Theator is implementing surgical learning systems to improve operative performance)

19. Improving Outcomes in Behavioral Health – With natural language processing, GA can analyze behavioral health sessions to identify more effective treatment interventions (Eleos uses NPL and AI to identify value based behavioral healthcare and reduce inefficient care)..

20. Reducing Disparities and Addressing Disabilities- GA will not only help identify where disparities in care exist through data analysis but it will also create solutions. Through targeted outreach, educational and behavioral strategies that are targeted to specific needs of communities, more effective health interventions can be implemented. (Companies like CareJourney and Datavant are using data from a variety of sources to identify opportunities for improvement and Voiceitt is using AI to facilitate better communication for those with severe speech disorders).

21. Reducing Gaps in Care- When it comes to chronic illness management, GA can more easily use data and algorhythms to identify gaps in care that often result in poorer outcomes for patients.

22. Early Intervention- GA can use unstructured data and image analyses to identify patients a risk that would benefit from early intervention. We are already seeing this with kidney disease, sepsis, early stroke identification, and even suicide prevention. (AIdoc is using GA to identify early intervention for patients with stoke and a number of other conditions)

23. Improving Point of Care Testing – GA will allow the smartphone to become an even more useful tool for diagnostic evaluations. With improved molecular testing and lateral flow analyses, GA will allow more sophisticated testing to be run in the home setting. (Ixlayer offers an enterprise system for managing data for point of care testing and TytoCare brings the ability to test right in the home).

24.. Reducing the Cost of Care- GA can help develop tools to identify “low value” care. GA will help already existing technology getter better at identifying care that is not appropriate or effective and channel resources into areas where effective care can best targeted.

25. Reducing Medical Errors- Using predictive modeling, GA can help identify before they occur and create early warning systems to alert healthcare professionals and patients (or caregivers) of high risk situations.(Sparta Science is a company using predictive data to identifying patients at risk for falls and in speeding rehabilitation).

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Whistleblower: Nurse testifies how during COVID-19 – a lot of VERY BAD MEDICINE provided

Posted on May 12, 2023 by Pharmaciststeve

Did the some million USA citizens really need to die from COVID-19 ?

This the second video that has come my way of nurses testifying of the “wrong medicine” that was provided during the early COVID-19 to pts in hospitals. The above hyperlink is a nurse testifying before some politicians/bureaucrats in Florida. The above video seems to be in front of a Federal Senate Committee.

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Federal Judge Dismisses Patient Death Charges in Opioid Trial of Dr. Thomas Sachy

Posted on May 11, 2023 by Pharmaciststeve

Federal Judge Dismisses Patient Death Charges in Opioid Trial of Dr. Thomas Sachy

Macon Physician Dr. Thomas Sachy Secures Dismissal of Charges that he Caused the Death of Two Pain Patients

https://ronaldwchapman.com/blog/sachy-dismissal

Dr. Thomas Sachy, a neuropsychiatrist who worked near Macon Georgia, was indicted in 2018 for operating a “pill mill” and causing the deaths of two patients. Both charges carry a mandatory minimum sentence of 20 years in prison – each. After a hard fought victory, Dr. Sachy will walk out of the federal courthouse in Columbus, GA a free man on May 11, 2023 after a five year battle with the federal government and DEA.

His attorneys, Ronald W. Chapman II and Meggan Sullivan are grateful that they could secure freedom for yet another physician targeted by the DEA.

The once well respected neuropsychiatrist was an expert forensic psychiatrist in many high-profile Georgia murder cases, physician board reviewer for the Georgia Board of Medicine and guest speaker for the Georgia Bar.

But in 2016 the DEA received an anonymous tip from a patient’s sister that spawned a DEA investigation. The investigation would land Dr. Thomas Sachy in the crosshairs of the federal government and a five year legal battle for causing the death of two patients and over-prescribing opioids to a Bibb County Deputy Sheriff.

Dr. Sachy Indicted and Jailed for Unlawful Distribution

In 2018, agents from the DEA burst through the door of the neuropsychiatrist’s practice and, as one patient would describe, held patients and staff at gunpoint. Dr. Sachy, the prominent Georgia Physician was arrested along with his 80 year old mother, his wife, and a nurse that worked at the practice.

After an undercover patient visit was unsuccessful in securing a prescription for opioid pain medication, the DEA pivoted and alleged that Dr. Sachy caused the death of two patients. Both patients suffered from significant heart issues.

Dr. Sachy was jailed for nearly three years after his arrest and was only able to secure his release after the landmark Supreme Court decision in Ruan v. United States which clarified the standard for when a physician could be convicted of unlawful distribution.

Under the new standard, Dr. Sachy proceeded to trial in the Middle District of Georgia in May of 2023.

The Trial of Dr. Sachy

The Government opened its case with the testimony of family members of the deceased who provided emotional testimony about their loved ones and their use of opioids. Federal prosecutors, however, ran into problems during the technical aspects of their case.

First, an expert anesthesiologist for the Government, Dr. Barry Straus testified that the standard for drug trafficking for a physician is the same as the standard applied by the Georgia Board.

During his thorough cross examination by Ronald W. Chapman II he attempted to convince the jury that any physician prescribing over 200 morphine milligrams per day of opiates that is not board certified in pain should be prosecuted. No such standard is found anywhere in the law or regulations surrounding opioid prescribing.

Defense Secures Exclusion of Expert Forensic Toxicologist Stacy Hail

The Government then attempted to establish that the opioids prescribed by Dr. Sachy caused the death of two patients – an effort that would later fail resulting in dismissal of the two death charges.

The dismissal came immediately after the testimony of Forensic Toxicologist Stacy Hail was excluded from trial. Dr. Hail began her testimony on the morning of May 9th armed with a whiteboard and marker, engaged in a preformative display in front of the jury where she described how opioids can cause death. Her testimony was abruptly halted by an objection from Ronald W. Chapman II after she testified that medication bottles was found near the body of one of the deceased patients. This was untrue and prosecutors would later admit that the error was due to Stacy Hail mixing up one of her many other assignments as an expert toxicologist.

The objection spawned defense arguments before District Judge Clay Land ultimately resulting in the exclusion of testimony from the medical examiner who conducted the “limited autopsy”. The defense objected to the introduction of toxicology reports that lacked a foundation laid by the lab tech preparing the report. Prosecutors admitted that prior to trial they had not secured the testimony of the lab tech and did not intend to call the person who tested the sample during their case – a violation of Dr. Sachy’s sixth amendment right to confrontation.

Late in the afternoon, its case dismantled by the exclusion of two important witnesses, the prosecution rose to admit that it lacked the basic foundational toxicology evidence needed to move forward with the charges.

The Government rested its case shortly after.

On May 9, 2023, seven days into the trial that was expected to last nearly a month, Judge Clay Land of the Middle District of Georgia dismissed two charges of the indictment which alleged that Dr. Sachy distributed controlled substances causing the death of two patients.

The Defense Calls Patients of Dr. Sachy Who Suffered from Debilitating Pain

Still remaining were charges that Dr. Sachy ran a drug involved premises, engaged in a conspiracy to unlawfully distribute, and unlawfully prescribed to three specific patients.

The next day the defense called 10 witnesses including former patients of Dr. Sachy who described their debilitating ailments, family members of deceased patients, an addictionologist who evaluated pain patients for Dr. Sachy. The defense began to erase a picture created by Federal Prosecutors that tolerance equates to addiction and that aberrant behaviors require dismissal. The brother of a patient who later committed suicide due to untreated pain provided emotionally charged testimony. The patient was abruptly refused pain medication following the arrest and indictment of two of his physicians. The witness described Dr. Sachy as his brother’s savior and told the jury that Dr. Sachy gave him some semblance of his life back.

Two other patients, a husband and wife, both testified after allegations by the Government’s expert Dr. Barry Straus, that it was inappropriate to see patients residing in the same household. The husband and wife duo testified that they both had severe pain, one suffering from fibromyalgia and another suffering from pain as a result of an accident that required him to be cut out of his car by EMS. Meggan Sullivan lead the examinations and walked the jury through the debilitating pain that Dr. Sachy’s patients suffered from.

Prosecutors Agree to Dismiss the Remaining Charges of Drug Conspiracy, Unlawful Drug Distribution, and Money Laundering

At the end of the first day of the Defense case that was expected to last three days and culminate in the testimony of Dr. Sachy’s expert witness Dr. James Murphy, the Federal Prosecutors approached Dr. Sachy with a resolution. The resolution would result in the dismissal of all charges in the indictment related to opioid distribution, no jail time, and the return of $1.2 million in assets seized by the Federal Government.

As a result of the agreement, Dr. Sachy walked out of the Federal Courthouse in Columbus Georgia a free man.

The result was secured by significant efforts from Dr. Sachy’s investigators CCG Healthcare, his attorneys Ronald W. Chapman and Meggan Sullivan and the hard working staff at Chapman Law Group.

Ronald W. Chapman II is a federal defense attorney, author of “Unraveling Federal Criminal Investigations” , and frequent TV news commentator who regularly defends physicians facing allegations of unlawful distribution. He is also the president of CCG Healthcare a healthcare consulting firm devoted to aiding physicians and health care practices with compliance to avoid career ending federal investigations and charges related to health care fraud and opioid distribution.

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