Chapter 12 — Exercises
How to use these. No answers are provided here. Items marked † have worked solutions in the instructor materials; everything else is for discussion, writing, or your own notebook. Several items ask you to look something up — that is deliberate, because §12.11's seventh rule is that everything in this chapter has a shelf life measured in months.
Ground rule, repeated: nothing in this chapter or these exercises is medical advice, and no exercise asks you to describe a dose, a preparation, or an injection technique. If an answer you are drafting starts to look like an instruction sheet, you have answered a different question.
A. Recall and definition
12.1 Name the four prices from §12.1 and state, for each, who pays it and whether it is publicly knowable.
12.2 What does a rebate do to the net price, and what does it do to the price paid by an uninsured person? Explain why those two answers differ.
12.3 † Define fill-finish and explain in three sentences why it, rather than peptide synthesis, was the binding constraint during the GLP-1 shortage.
12.4 State the difference between a 503A compounding pharmacy and a 503B outsourcing facility across four dimensions: prescription requirement, scale, oversight, and manufacturing standard.
12.5 Complete the sentence and then explain why it matters: "Compounded products are not FDA-approved, which means nobody has reviewed them for __ or ____."
12.6 † Semaglutide sodium, semaglutide acetate, and semaglutide base. Which is in the approved products, and what did regulators say about the other two?
12.7 Define off-label prescribing. Then state the one-sentence difference between off-label and unapproved.
12.8 Reproduce, from memory if you can, the label clause that follows the eligibility criteria for GLP-1 agonists in weight management. What is that clause actually describing?
12.9 † State Chapter 11's five features of lethal rationing, and mark which ones GLP-1 agonists share.
12.10 Define set point and metabolic adaptation, and state the relationship between them.
12.11 What is the inverse care law, and in what year was it described?
B. Applied reasoning
12.12 † A headline reports that a GLP-1 agonist "cuts heart attacks and strokes by 20 percent." Using the SELECT figures from §12.2, rewrite that headline in a form that would satisfy this book's standards, in no more than 25 words. Then explain what information the original headline withheld and who is harmed by the omission.
12.13 A friend says: "Other countries pay a third of what we pay. That proves the price is arbitrary." Identify the part of that claim you agree with and the inference you would resist, and name the mechanism that actually explains the difference.
12.14 A plan covers a GLP-1 agonist but requires prior authorization, documented eligibility, a failed trial of a cheaper agent, and enrollment in a coaching program. For each requirement, give the clinical rationale a medical director would offer and the attrition effect §12.2 predicts.
12.15 † A manufacturer announces a very large investment in new production capacity. A commentator concludes that the shortage will end within the year. Using §12.3, explain what the commentator has assumed and what question they should have asked instead.
12.16 A clinic advertises a compounded GLP-1 product "with added B12 for energy." Using §12.5, identify at least three separate evidentiary problems introduced by the word "added."
12.17 Rank these four uses of a GLP-1 agonist on §12.6's off-label spectrum, and justify each placement: (a) an approved indication with documented eligibility; (b) a population studied in published randomized trials but not yet in the label; (c) a use supported only by a plausible receptor mechanism; (d) a use requested by the patient and approved by a form.
12.18 † A telehealth intake form asks for height, weight, a list of current medications, and a yes/no question about thyroid cancer in the family. Using §12.7 and §12.10, name three things the form does not ask that a clinician would, and explain what could go wrong in each case.
12.19 Someone argues that because GLP-1 agonists work, obesity must be a GLP-1 deficiency. Name the reasoning error, then construct two counterexamples from outside metabolism.
12.20 A large employer drops weight-management drugs from its formulary at renewal, affecting several thousand covered lives at once. Sketch what happens to that population over the following five years, and name the specific reason the resulting harm will not appear in any published statistic.
12.21 † Take the SELECT absolute risk reduction and the number needed to treat. Explain, without computing any new number, why the same relative risk reduction would produce a much larger number needed to treat in a lower-risk population — and what that implies about extrapolating the trial to people without established cardiovascular disease.
C. Explain this to a friend
For each of these, write for a specific person with no scientific background. No jargon you have not defined for them in the same paragraph. Aim for under 200 words each.
12.22 Your sibling asks why their neighbour pays almost nothing for the same drug that costs them a fortune. Explain the four prices without using the phrase "pharmacy benefit manager."
12.23 A colleague says compounded semaglutide is "the same thing, just cheaper." Explain the salt form issue and the missing device in a way that does not sound like an accusation against anyone who used it.
12.24 † Your parent says, "These drugs are pointless — the weight all comes back when you stop." Agree with the factual part, then explain why the conclusion does not follow. Use one comparison from outside weight medicine.
12.25 A friend who is starting therapy through a website asks whether "medically supervised" means they are in good hands. Give them three questions to ask and explain what a bad answer would sound like.
12.26 Someone tells you obesity is "just calories in, calories out." Steelman their position in two sentences before you say anything else. Then add the one thing that position cannot explain.
D. Judgment and ethics
These have no correct answers. They have better and worse arguments. Write the strongest version of the position you disagree with before you write your own.
12.27 † Take the three compounded-semaglutide users from §12.4. Write a separate paragraph on each, and in every paragraph name explicitly the alternative you are holding that person to. Then answer this: if your three judgments came out identical, what did you actually judge?
12.28 A payer with a fixed budget must choose between covering obesity pharmacotherapy for its whole eligible population and funding something else — a mental health expansion, a lower deductible, a maternity program. Argue the payer's case at its strongest. Then argue against it at its strongest. Do not resolve the conflict; name what a resolution would require.
12.29 During a shortage, should there be an allocation rule, and if so who should write it? Consider at least three candidate rule-makers (manufacturer, regulator, pharmacy, professional society) and give one real objection to each.
12.30 Chapter 7 described the incretin program as a publicly funded success. Argue that the public is entitled to something in return. Then argue that it already received it. Then say which argument you find stronger and, specifically, what evidence would change your mind.
12.31 † Present all four positions from §12.9 as their strongest advocates would present them, in roughly 150 words each, without indicating which you hold. Then, in a separate paragraph clearly labelled as your own view, say where you land and why. The exercise is the separation, not the conclusion.
12.32 Is it defensible for a company to employ the clinician who decides whether a patient needs the product that company sells? Argue both sides. Then name the safeguard that would most change your answer, and say whether you have ever seen it implemented.
E. Evidence Dossier extension
12.33 Complete Field 10 (Status) for every peptide in your dossier. Every entry must carry a date checked and a list of the specific sources you would re-check. An undated Field 10 is not information.
12.34 Pick the peptide in your dossier whose Field 10 was hardest to fill. Write a paragraph on why it was hard — missing information is itself a finding, and in Part III it is often the main one.
12.35 For one dossier peptide, write two versions of the "Who is selling it" line: one for the most regulated supplier you can identify, one for the least. Then state what you would need in order to tell which one a given vial came from.
12.36 Return to the confidence ratings you wrote in Chapter 1, Step 3. For each dossier peptide, note whether anything in this chapter changed your confidence — and if so, whether it changed your view of the evidence or of the access situation. Those are different columns and this chapter is the place where people most often confuse them.