Big Pharma is testing crucial boundaries in the way that the nation determines the safety and effectiveness of prescription medications. And regulators, for patients’ sake, need to shove back — hard.

The concerning incidents involve “pay to play” clinical trials and “manipulated” data submitted to the federal Food and Drug Administration by maker Novartis as part of the approval process for a gene therapy drug with a sky-high price.

Neither instance, officials insist, had immediate effects in endangering patients. But both show extreme practices and conduct that regulators should slam to a halt.

The FDA already has rebuked Novartis and said the company may face civil or criminal penalties for inaccurate information it submitted to win approval for its drug Zolgensma, which the Washington Post reported is “used for children less than 2-years-old with spinal muscular atrophy, a leading genetic cause of infant death.”

Zolgensma is a one-time treatment. But it comes at a whopping cost: $2.1 million. Novartis said it knows of 700 youngsters with the disease who might benefit from its therapy, which also could be helpful to another 400 children annually. As the Washington Post noted:

“Spinal muscular atrophy is considered an extremely rare disease, affecting about 30 new patients a month. It is caused by a defective gene that is supposed to allow the body to maintain cells called motor neurons. Without a properly functioning gene, infants typically die or live on respirators and other life support.”

What’s galling about this case is that the FDA says it worked closely with Novartis to expedite a promising therapy for a rare and problematic condition affecting children. The company told the FDA on June 28 that it had learned of problems in its data. That was more than a month after the agency approved Zolgensma and four months after Novartis first knew of issues in studies foundational to getting its drug FDA approved.  As the New York Times reported:

“The problems involved experiments on mice used in early phases of the research. An FDA inspection report dated July 24 to Aug. 2, 2019 noted lapses and discrepancies in record-keeping by the company, and improper procedures in quality control in gathering data on the mice. In some instances, the report said, records stating how long the mice lived ‘were different from the actual value,’ and in four cases ‘discrepancies of greater than one day were noted (ranging from 2 to 19 days).’ The FDA said the data were ‘mismanaged’ or ‘manipulated,’ and declined to say whether the information was deliberately falsified.”

Novartis officials have defended their drug, its effectiveness, quality, and safety, and said they have investigated abuses that prompted the FDA rebuke. The company’s CEO said Novartis has fired some scientists involved in this matter, which is but the latest of several scandals involving the company.

Novartis and its subsidiaries also have been caught up in: allegations of price-fixing and improper marketing of its generic drugs; another and separate concern about data in a Japanese unit; and for hiring and paying more than $1 million to lawyer Michael Cohen. He was President Trump’s personal attorney and has testified that companies paid him because of his contacts and knowledge of the administration. He has been convicted and imprisoned on federal charges of tax fraud, making false statements to Congress, and violating campaign finance laws for facilitating hush money payments to porn actress Stormy Daniels as well as Playboy model Karen McDougal to silence their allegations of past affairs with Trump.

Pay-to-play clinical trials

The disclosure of Novartis’ misconduct — which also underscores challenges in FDA oversight of Big Pharma — occurred even as regulators are grappling with the rise of a new issue in a bedrock of prescription medications’ rigorous approval process: clinical trials.

Stat, a health and medical news site, reported that medical scientists and federal officials are growing concerned over researchers’ efforts to charge patients to enroll in clinical trials, which are supposed to provide an objective, “gold standard” process to determine the safety and effectiveness of medical therapies, especially prescription drugs.

Because they involve human subjects, clinical trials are supposed to be subject to rigorous oversight, which includes legal and ethical standards, many of which are in theory safeguarded by independent Institutional Review Boards (IRBs). These often include not only doctors, medical scientists, and officials of hospitals and research institutions. They also may include prominent community members, religious leaders, and individuals concerned with ethics. But do IRBs, federal officials, and the bona fide medical-scientific research community possess the time, energy, resources, and clout — especially legal and financial resources — to prevent “pay to play” abuses that could degrade the independence, authority, and value of clinical trials?

Drug makers and investigators cover some costs for patients enrolled, with clinical trials needing to disclose these as part of their conflict of interest statements about their results. Researchers have come under criticism that wealthier sick patients may be able to travel or to seek out trials far from their homes, potentially qualifying for studies that the less affluent could not access.

Stat, however, reported that researchers fear that the validity of clinical trials may be thrown in dispute when patients pay to be in them, including: putting up $8,000 to $250,000 to get infusions of blood from young people, purported as a “treatment” for aging, or forking over $7,200 in a “therapy” for autism.

What’s the problem? As Stat reported:

“Experts say these trials are ethically fraught for a number of reasons: At worst, they run the risk of being a guise for an enterprise looking to profit from desperate patients. But even when intentions are sound, the trials are likely to only enroll those patients who can afford to participate, thereby skewing the results. There could also be a weak study design, without blinding or a control group, because patients would likely be reluctant to pay for a placebo. And they may reinforce the common misconception among patients that clinical trials are a route to accessing treatments that are guaranteed to help them.”

To be sure, the blood infusion “therapy” has been denounced as medical humbug, and at least one firm purporting to provide it and test it at a cost to patients halted its services after receiving FDA warnings. The autism “stem cell” trial was proposed offshore in an area not subject to U.S. regulation. Still, do Americans really want to put blind trust in profit-seeking Big Pharma to do the right thing about patients’ safety and the quality and effectiveness of  drugs that throw off fat money?

In my practice, I see not only the harms that patients suffer while seeking medical services, but also the havoc that can be wreaked on them and their loved ones by dangerous drugs. Big Pharma and medical device makers — with the help of doctors, hospitals, pro-business politicians, and, yes, desperate patients — already have slashed at regulation and oversight of their wares, arguing that medical innovations need to be raced to markets.

But the factual, scientific rigor that has protected Americans from prescription drug or medical device harms — think Thalidomide or opioids — is under incessant attack, notably by Big Pharma. As the U.S. oversight system exists, regulators must rely to a large degree on the very industry they are supposed to watchdog to conduct crucial tests and clinical trials of their products to win approvals. Regulators, though, now go along to get along, allowing drug makers, for example, to test for “surrogate endpoints,” showing not that their drugs extend or improve patients’ lives but that they appear to address a disease issue or symptom like slowing tumor growth. FDA officials may be more, for patients’ purposes, house tabbies than growling watchdogs. Why not, when Congress, in the name of fiscal efficiency, has made a big part of the agency budget fees that drug makers pay to get products approved?

Experimentation with late-stage cancer patients

Jane Brody, in a New York Times column, discussed the terrible toll that Big Pharma hype and its relentless push for profits takes on cancer patients. While it is true that great progress has occurred in treatment of this disease, it also is a fact that certain cancers persist as killers. Researchers are racing to develop therapies to help, notably drugs with bankrupting costs and spare good outcomes. Brody reported on the work of Dr. Azra Raza, director of the Myelodysplastic Syndrome Center at Columbia University. She has argued in her forthcoming book The First Cell, and the Human Costs of Pursuing Cancer to the Last:

“Most new cancer drugs add mere months to a patient’s life at an agonizing physical and financial cost. For example … the drug Tarceva prolongs survival of those with pancreatic cancer by an average of 12 days at a cost of $26,000 a year, not to mention dreadful side effects. Still, buying time can be meaningful to many patients, who may use it to get their affairs in order, reconcile with estranged family or friends, and say meaningful goodbyes… But experts who focus on quality of life maintain that it should be up to patients to decide if continued treatment is worth the costs. And not just personal costs but also dollar costs, given that some new therapies cost hundreds of thousands of dollars a year.”

Brody also touches on a troubling reality: Many end-stage cancer patients, out of desperation but with courage and altruism, too, assent to doctors’ recommendations that they try experimental treatments that may benefit not them as much as science and others. Good for them, if they, of course, have given informed consent. That’s a basic right that patients have. It means they are told clearly and fully all the important facts they need to make an intelligent decision about what treatments to have, where to get them, and from whom.

Still, this is yet another leaky area of testing involving patients. This is, alas, a crucial and irreplaceable (for now) part of medical science. So, lawmakers and regulators, as well as medical scientists, doctors, hospitals, and research institutions must step up and safeguard patients, clinical trials, and the accuracy and truthfulness of investigative data and information. A bulwark for patients — their trust in the safety, quality, and effectiveness of costly prescription drugs — cannot be broken down by Big Pharma and extremists in the field.